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Alhusayen R, Dienes S, Lam M, Alavi A, Alikhan A, Aleshin M, Bahashwan E, Daveluy S, Goldfarb N, Garg A, Gulliver W, Jaleel T, Kimball AB, Kirchhof MG, Kirby J, Lenczowski J, Lev-Tov H, Lowes MA, Lara-Corrales I, Micheletti R, Okun M, Orenstein L, Poelman S, Piguet V, Porter M, Resnik B, Sibbald C, Shi V, Sayed C, Wong SM, Zaenglein A, Veillette H, Hsiao JL, Naik HB. North American clinical practice guidelines for the medical management of hidradenitis suppurativa in special patient populations. J Am Acad Dermatol 2025; 92:825-852. [PMID: 39725212 DOI: 10.1016/j.jaad.2024.11.071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 11/16/2024] [Accepted: 11/23/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND Hidradenitis suppurativa (HS) affects different patient populations that require unique considerations in their management. However, no HS guidelines for these populations exist. OBJECTIVE To provide evidence-based consensus recommendations for patients with HS in 7 special patient populations: (i) pregnancy, (ii) breastfeeding, (iii) pediatrics, (iv) malignancy, (v) tuberculosis infection, (vi) hepatitis B or C infection, and (vii) HIV disease. METHODS Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation system to ascertain level of evidence and selected through a modified Delphi consensus process. RESULTS One hundred eighteen expert consensus statements are provided for the management of patients with HS across these 7 special patient populations.
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Affiliation(s)
- Raed Alhusayen
- Sunnybrook Research Institute, Toronto, Ontario, Canada; Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
| | - Serena Dienes
- Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Megan Lam
- Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Afsaneh Alavi
- Department of Dermatology, Mayo Clinic, Rochester, Minnesota
| | - Ali Alikhan
- Sutter Medical Foundation, Sacramento, California
| | - Maria Aleshin
- Department of Dermatology, Stanford University School of Medicine, Stanford, California
| | - Emad Bahashwan
- Division of Dermatology, Faculty of Medicine, University of Bisha, Bisha, Saudi Arabia
| | - Steve Daveluy
- Department of Dermatology, Wayne State University School of Medicine, Detroit, Michigan
| | - Noah Goldfarb
- Department of Dermatology, University of Minnesota, Minneapolis, Minnesota
| | - Amit Garg
- Department of Dermatology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, New York
| | - Wayne Gulliver
- Department of Dermatology, Memorial University of Newfoundland, St. John's, Canada
| | - Tarannum Jaleel
- Department of Dermatology, Duke University School of Medicine, Durham, North Carolina
| | - Alexa B Kimball
- Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Department of Dermatology, Harvard Medical School, Boston, Massachusetts
| | - Mark G Kirchhof
- Division of Dermatology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Division of Dermatology, Department of Medicine, Ottawa Hospital, Ottawa, Ontario, Canada
| | - Joslyn Kirby
- Incyte Corporation, Wilmington, Delaware; Department of Dermatology, Penn State Health, Hershey, Pennsylvania
| | | | - Hadar Lev-Tov
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, Florida
| | - Michelle A Lowes
- Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York
| | - Irene Lara-Corrales
- Division of Dermatology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Robert Micheletti
- Departments of Dermatology and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Lauren Orenstein
- Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia
| | - Susan Poelman
- Division of Dermatology, University of Calgary and Beacon Dermatology, Calgary, Alberta, Canada
| | - Vincent Piguet
- Division of Dermatology, Department of Medicine, University of Toronto and Women's College Hospital, Toronto, Ontario, Canada
| | - Martina Porter
- Department of Dermatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - Barry Resnik
- Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, Florida; Resnik Skin Institute, Miami, Florida
| | - Cathryn Sibbald
- Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Dermatology, Department of Pediatrics, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Vivian Shi
- Department of Dermatology, University of Washington, Seattle, Washington
| | - Christopher Sayed
- Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Se Mang Wong
- Department of Dermatology, University of British Columbia, Vancouver, British Columbia, Canada
| | - Andrea Zaenglein
- Department of Dermatology, Penn State Health, Hershey, Pennsylvania; Penn State Children's Hospital, Hershey, Pennsylvania
| | - Helene Veillette
- Division of Dermatology, Department of Medicine, CHU de Québec-Université Laval, Québec, Canada
| | - Jennifer L Hsiao
- Department of Dermatology, University of Southern California, Los Angeles, California
| | - Haley B Naik
- Department of Dermatology, University of California, San Francisco, California
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Caballero-Mateos AM, Quesada-Caballero M, Cañadas-De la Fuente GA, Caballero-Vázquez A, Contreras-Chova F. IBD and Motherhood: A Journey through Conception, Pregnancy and Beyond. J Clin Med 2023; 12:6192. [PMID: 37834837 PMCID: PMC10573266 DOI: 10.3390/jcm12196192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 09/14/2023] [Accepted: 09/19/2023] [Indexed: 10/15/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.
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Ahn SM, Joo YB, Kim YJ, Bang SY, Lee HS. Pregnancy Outcomes Associated With Biologic Agent Exposure in Patients With Several Rheumatic Diseases and Inflammatory Bowel Diseases. J Korean Med Sci 2023; 38:e172. [PMID: 37272561 PMCID: PMC10244022 DOI: 10.3346/jkms.2023.38.e172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 02/21/2023] [Indexed: 06/06/2023] Open
Abstract
BACKGROUND This study aimed to analyze pregnancy outcomes based on biologic agents use in women using the nationwide population-based database. METHODS The study used the claims database to identify women of childbearing age with several rheumatic (rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis) and inflammatory bowel diseases (Crohn's disease and ulcerative colitis) who had pregnancy-related codes between January 2010 and December 2019. We analyzed live births and adverse pregnancy outcomes based on the previous use of biologics. We also stratified the patients according to duration of biologic agent exposure before pregnancy and the use of biologics during pregnancy to analyze the pregnancy outcomes by subgroups. RESULTS We identified 4,787 patients with pregnancy events. Among them, 1,034 (21.6%) used biologics before pregnancy. Live birth rate was not different between the biologics group and biologics naïve group (75.0% vs. 75.2%). Multivariate analyses showed that biologics use was associated with higher risk of intrauterine growth retardation (odds ratio [OR], 1.780) and lower risk of gestational diabetes mellitus (OR, 0.776) compared with biologics naïve. Biologics use during pregnancy was associated with higher risk of preterm delivery (OR, 1.859), preeclampsia/eclampsia (OR, 1.762), intrauterine growth retardation (OR, 3.487), and cesarean section (OR, 1.831), but lower risk of fetal loss (OR, 0.274) compared with biologics naïve. CONCLUSIONS Although there was no difference in live birth rate between the biologics group and biologics naïve group, biologics use seems to be associated with several adverse pregnancy outcomes, especially in patients with biologics during pregnancy. Therefore, patients with biologics during pregnancy need to be carefully observed for adverse pregnancy outcomes.
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Affiliation(s)
- Soo Min Ahn
- Division of Rheumatology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Bin Joo
- Division of Rheumatology, Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
- Hanyang University Institute for Rheumatology Research, Seoul, Korea
| | - Yun Jin Kim
- Biostatistical Consulting and Research Lab, Medical Research Collaborating Center, Hanyang University, Seoul, Korea
| | - So-Young Bang
- Division of Rheumatology, Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
- Hanyang University Institute for Rheumatology Research, Seoul, Korea
| | - Hye-Soon Lee
- Division of Rheumatology, Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
- Hanyang University Institute for Rheumatology Research, Seoul, Korea.
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Grigorescu RR, Husar-Sburlan IA, Rosulescu G, Bobirca A, Cerban R, Bobirca F, Florescu MM. Pregnancy in Patients with Inflammatory Bowel Diseases-A Literature Review. Life (Basel) 2023; 13:475. [PMID: 36836832 PMCID: PMC9961380 DOI: 10.3390/life13020475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 02/03/2023] [Accepted: 02/04/2023] [Indexed: 02/11/2023] Open
Abstract
In recent years, we have faced an increasing incidence of inflammatory bowel disease (IBD), especially among young people, affecting them during their reproductive years. The paucity of data and reduced knowledge regarding the evolution of the disease during pregnancy and the adverse effects of the therapy on the mother and infant increase voluntary childlessness in this group of patients. Depending on the type of IBD, severity and surgical or medical management, this can negatively affect the pregnancy. C-sections and the risk of low-birth-weight babies are higher in women with IBD, independent of active/inactive disease, while preterm birth, stillbirth and miscarriage are associated with disease activity. In the last period, medicinal therapy has evolved, and new molecules have been developed for better control of the lesions, but the effect on pregnancy and breastfeeding is still controversial. We conducted this review by studying the literature and recent research in order to have a better image of the practical management of IBD during pregnancy.
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Affiliation(s)
| | | | - Georgiana Rosulescu
- Gastroenterology Department, “Sfanta Maria” Hospital, 011172 Bucharest, Romania
| | - Anca Bobirca
- Department of Internal Medicine and Rheumatology, Dr. I. Cantacuzino Clinical Hospital, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Razvan Cerban
- Center for Digestive Disease and Liver Transplantation, Fundeni Clinical Institute, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Florin Bobirca
- Surgery Department, Dr. Ion Cantacuzino Clinical Hospital, 011437 Bucharest, Romania
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5
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Donovan B, Spiel M. Inflammatory Bowel Disease in the Childbearing Adult and Newborn. Neoreviews 2023; 24:10-23. [PMID: 36587009 DOI: 10.1542/neo.24-1-e10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Inflammatory bowel disease (IBD) often affects people in their childbearing years and has implications for pregnancy outcomes, particularly as related to increased risk of preterm delivery and effects of immunosuppressive medications on the fetus. Ideally, people with IBD should attempt conception at a time when their disease is in remission to optimize pregnancy outcomes and reduce risks of flares. Generally, pregnant individuals should continue immunosuppressive medications throughout gestation in an attempt to control the disease. Maternal risks of IBD in pregnancy include exacerbated anemia, disease flare, cesarean delivery, and treatment risks. Fetal and neonatal risks include preterm birth, low birthweight, and medication exposures. There are too few clinical trials that include pregnant or breastfeeding patients to analyze the risk/benefit profile of immunosuppressive medications for IBD treatment during pregnancy, limiting the amount of data available to guide medical treatment in this population. More studies are needed on IBD therapies, particularly as more biologics are developed and become the mainstay of treatment. Neonatal clinicians should be aware of in utero medication exposure to help guide decisions regarding newborn care.
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Affiliation(s)
- Bridget Donovan
- Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA
- Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA
| | - Melissa Spiel
- Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA
- Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA
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Russell MD, Dey M, Flint J, Davie P, Allen A, Crossley A, Frishman M, Gayed M, Hodson K, Khamashta M, Moore L, Panchal S, Piper M, Reid C, Saxby K, Schreiber K, Senvar N, Tosounidou S, van de Venne M, Warburton L, Williams D, Yee CS, Gordon C, Giles I, Roddy E, Armon K, Astell L, Cotton C, Davidson A, Fordham S, Jones C, Joyce C, Kuttikat A, McLaren Z, Merrison K, Mewar D, Mootoo A, Williams E, BSR Standards, Audit and Guidelines Working Group. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2022; 62:e48-e88. [PMID: 36318966 PMCID: PMC10070073 DOI: 10.1093/rheumatology/keac551] [Citation(s) in RCA: 90] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 09/15/2022] [Indexed: 11/07/2022] Open
Affiliation(s)
- Mark D Russell
- Centre for Rheumatic Diseases, King's College London, London, UK
| | - Mrinalini Dey
- Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Julia Flint
- Department of Rheumatology, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Shropshire, UK
| | - Philippa Davie
- Centre for Rheumatic Diseases, King's College London, London, UK
| | - Alexander Allen
- Clinical Affairs, British Society for Rheumatology, London, UK
| | | | - Margreta Frishman
- Rheumatology, North Middlesex University Hospital NHS Trust, London, UK
| | - Mary Gayed
- Rheumatology, Sandwell and West Birmingham Hospitals, Birmingham, UK
| | | | - Munther Khamashta
- Lupus Research Unit, Division of Women's Health, King's College London, London, UK
| | - Louise Moore
- Rheumatic and Musculoskeletal Disease Unit, Our Lady's Hospice and Care Service, Dublin, Ireland
| | - Sonia Panchal
- Department of Rheumatology, South Warwickshire NHS Foundation Trust, Warwickshire, UK
| | - Madeleine Piper
- Royal National Hospital for Rheumatic Diseases, Royal United Hospital, Bath, UK
| | | | - Katherine Saxby
- Pharmacy, University College London Hospitals NHS Foundation Trust, London, UK
| | - Karen Schreiber
- Thrombosis and Haemostasis, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Rheumatology, Danish Hospital for Rheumatic Diseases, Sonderborg, Denmark.,Department of Regional Health Research (IRS), University of Southern Denmark, Odense, Denmark
| | - Naz Senvar
- Obstetrics and Gynaecology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Sofia Tosounidou
- Lupus UK Centre of Excellence, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK
| | | | | | - David Williams
- Obstetrics, University College London Hospitals NHS Foundation Trust, London, UK
| | - Chee-Seng Yee
- Department of Rheumatology, Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust, Doncaster, UK
| | - Caroline Gordon
- Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
| | - Ian Giles
- Centre for Rheumatology, Division of Medicine, University College London, London, UK
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Mahadevan U, Naureckas S, Tikhonov I, Wang Y, Lin CB, Geldhof A, van der Woude CJ. Pregnancy outcomes following periconceptional or gestational exposure to ustekinumab: Review of cases reported to the manufacturer's global safety database. Aliment Pharmacol Ther 2022; 56:477-490. [PMID: 35560249 DOI: 10.1111/apt.16960] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/17/2022] [Accepted: 04/22/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND Ustekinumab, a human immunoglobulin G1 monoclonal antibody that binds to and inhibits interleukin (IL)-12/IL-23, is indicated for multiple immune-mediated diseases. Ustekinumab is actively transported across the placenta and theoretically could impact pregnancy outcomes. Limited data on pregnancy outcomes with ustekinumab exposure are available. AIM To assess pregnancy outcomes in patients exposed to ustekinumab during pregnancy METHODS: Cumulative data on medically confirmed ustekinumab-exposed pregnancies from the manufacturer's Global Safety Database were summarised. Descriptive data for pregnancy outcomes were presented overall and by patient subgroups. RESULTS As of 31 August 2020, 408 medically confirmed, prospective, maternal ustekinumab-exposed pregnancies with reported outcomes were identified. The mean maternal age was 31 years. Of the 420 pregnancy outcomes (including 4 sets of twins),a , b 340 (81%) were live births, 51 (12.1%) spontaneous abortions, 25 (6%) elective/induced abortions, 3 (0.7%) stillbirths and 1 (0.2%) ongoing pregnancy with foetal congenital anomaly (CA). Among 340 live births, 33 (9.7%) were born pre-term. The rate of major CAs was similar by indication (Crohn's disease vs psoriasis), ustekinumab dose (45 mg vs 90 mg) and timing and duration of maternal exposure to ustekinumab. Prospective outcomes of pregnancies with paternal periconceptional ustekinumab exposure (n = 87) included 92% live births (1.2% major CA), 5.7% spontaneous abortions and 2.3% elective/induced abortions. CONCLUSIONS Rates of adverse pregnancy outcomes or CAs with ustekinumab exposure were consistent with rates reported for the US general population and do not suggest a higher risk associated with maternal or paternal exposure to ustekinumab.
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Affiliation(s)
- Uma Mahadevan
- University of California San Francisco, San Francisco, California, USA
| | - Saule Naureckas
- Janssen Research and Development, LLC, Raritan, New Jersey, USA
| | - Ilia Tikhonov
- Janssen Research and Development, LLC, Raritan, New Jersey, USA
| | - Yiting Wang
- Janssen Research and Development, LLC, Spring House, Pennsylvania, USA
| | - Connie B Lin
- Janssen Research and Development, LLC, Horsham, Pennsylvania, USA
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Abstract
Pregnancy is a complex biological process. The establishment and maintenance of foetal-maternal interface are pivotal events. Decidual immune cells and inflammatory cytokines play indispensable roles in the foetal-maternal interface. The disfunction of decidual immune cells leads to adverse pregnancy outcome. Tumour necrosis factor (TNF)-α, a common inflammatory cytokine, has critical roles in different stages of normal pregnancy process. However, the relationship between the disorder of TNF-α and adverse pregnancy outcomes, including preeclampsia (PE), intrauterine growth restriction (IUGR), spontaneous abortion (SA), preterm birth and so on, is still indefinite. In this review, we thoroughly reviewed the effect of TNF-α disorder on pathological conditions. Moreover, we summarized the reports about the adverse pregnancy outcomes (PE, IUGR, SA and preterm birth) of using anti-TNF-α drugs (infliximab, etanercept and adalimumab, certolizumab and golimumab) currently in the clinical studies. Overall, IUGR, SA and preterm birth are the most common adverse pregnancy outcomes of anti-TNF-α drugs. Our review may provide insight for the immunological treatment of pregnancy-related complication, and help practitioners make informed decisions based on the current evidences.
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9
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Volger S, Scherl E. Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy. Clin Gastroenterol Hepatol 2022; 20:962-963. [PMID: 33864935 DOI: 10.1016/j.cgh.2021.04.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 04/10/2021] [Indexed: 02/07/2023]
Affiliation(s)
- Sheri Volger
- Janssen Research & Development, LLC, Spring House, Pennsylvania
| | - Ellen Scherl
- New York-Presbyterian Weill Cornell Medical Center, New York, New York
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10
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Nielsen OH, Gubatan J, Juhl CB. Reply. Clin Gastroenterol Hepatol 2022; 20:963-964. [PMID: 33989789 DOI: 10.1016/j.cgh.2021.05.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/05/2021] [Accepted: 05/07/2021] [Indexed: 02/07/2023]
Affiliation(s)
- Ole Haagen Nielsen
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
| | - John Gubatan
- Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, California
| | - Carsten Bogh Juhl
- Cochrane Musculoskeletal Group, Research Unit for Musculoskeletal Function, University of Southern Denmark, Southern Denmark, Denmark
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11
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Theodoraki E, Orfanoudaki E, Foteinogiannopoulou K, Andreou NP, Gazouli M, Koutroubakis IE. Effect of antinuclear antibodies on pharmacokinetics of anti-TNF therapy in patients with inflammatory bowel disease. Int J Colorectal Dis 2022; 37:639-646. [PMID: 35013823 DOI: 10.1007/s00384-021-04091-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/28/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA. METHODS Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. RESULTS One hundred two IBD patients under maintenance therapy with IFX or ADA were enrolled. Of these, 53 (52%) were ANA positive with 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity was found to be correlated with age (P = 0.008), female gender (P = 0.03), duration of treatment (P = 0.06), arthralgias (P = 0.04) and TLs (P = 0.005). However, in multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P = 0.04 and P = = 0.006, respectively). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. CONCLUSIONS In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs. The clinical significance of this finding remains to be defined in future larger prospective studies.
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Affiliation(s)
- Eirini Theodoraki
- Department of Gastroenterology, Medical School, University Hospital of Heraklion, University of Crete, P.O. BOX 1352, 71110, Heraklion, Crete, Greece
| | - Eleni Orfanoudaki
- Department of Gastroenterology, Medical School, University Hospital of Heraklion, University of Crete, P.O. BOX 1352, 71110, Heraklion, Crete, Greece
| | - Kalliopi Foteinogiannopoulou
- Department of Gastroenterology, Medical School, University Hospital of Heraklion, University of Crete, P.O. BOX 1352, 71110, Heraklion, Crete, Greece
| | - Nikolaos-Panagiotis Andreou
- Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Gazouli
- Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis E Koutroubakis
- Department of Gastroenterology, Medical School, University Hospital of Heraklion, University of Crete, P.O. BOX 1352, 71110, Heraklion, Crete, Greece.
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12
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Nielsen OH, Gubatan JM, Juhl CB, Streett SE, Maxwell C. Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2022; 20:74-87.e3. [PMID: 32931960 DOI: 10.1016/j.cgh.2020.09.021] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 09/01/2020] [Accepted: 09/09/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Biologics are used routinely in pregnant women with inflammatory bowel disease (IBD), but large-scale data reporting adverse pregnancy outcomes among biologic users are lacking. We sought to estimate the prevalence of adverse pregnancy outcomes in women with IBD on biologic therapies. METHODS We searched major databases from inception to June 2020 for studies estimating the prevalence of adverse pregnancy outcomes in IBD when using biologics (anti-tumor necrosis factor [TNF], anti-integrins, and anticytokines). Prevalence and relative risk (RR) were pooled using a random-effects model. RESULTS Forty-eight studies were included in the meta-analysis comprising 6963 patients. Biologic therapy in IBD pregnancies was associated with a pooled prevalence of 8% (95% CI, 6%-10%; I2 = 87.4%) for early pregnancy loss, 9% (95% CI, 7%-11%; I2 = 89.9%) for preterm birth, 0% (95% CI, 0%-0%; I2 = 0%) for stillbirth, 8% (95% CI, 5%-10%; I2 = 87.0%) for low birth weight, and 1% (95% CI, 1%-2%; I2 = 78.3%) for congenital malformations. These rates are comparable with those published in the general population. In subgroup analyses of a small number of studies, the prevalence of early pregnancy loss and preterm birth were higher in vedolizumab vs anti-TNF users. Meta-regression did not show an association of disease activity or concomitant thiopurine on adverse outcomes. Continued TNF inhibitor use during the third trimester was not associated with risk of preterm birth (RR, 1.41; 95% CI, 0.77-2.60; I2 = 0%), low birth weight (RR, 1.32; 95% CI, 0.80-2.18; I2 = 0%), or congenital malformations (RR, 1.28; 95% CI, 0.47-3.49; I2 = 0%). CONCLUSIONS Adverse pregnancy outcomes among pregnant IBD women using biologics are comparable with that of the general population. PROSPERO protocol #CRD42019135721.
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Affiliation(s)
- Ole Haagen Nielsen
- Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
| | - John Mark Gubatan
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Carsten Bogh Juhl
- Research Unit for Musculoskeletal Function and Physiotherapy, University of Southern Denmark, Odense, Denmark; Department of Physiotherapy and Occupational Therapy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Sarah Elizabeth Streett
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California
| | - Cynthia Maxwell
- Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Ontario, Canada
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13
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Wang H, Chen F, Hu Y, Shen M. Adverse Pregnancy Outcomes Following Exposure to Biologics in Women With Crohn's Disease: A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8:753088. [PMID: 34760901 PMCID: PMC8573108 DOI: 10.3389/fmed.2021.753088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 09/27/2021] [Indexed: 11/13/2022] Open
Abstract
Crohn's disease is a chronic disease, which commonly affects women during their reproductive years. Poorly treated Crohn's disease is associated with adverse pregnancy outcomes. Biologics, a group of therapeutic drugs targeting inflammatory mediators including anti-TNF, anti-integrins and anti-interleukins, are increasingly used in pregnant women with Crohn's disease, exposing both the women and their fetuses to treatment-related complications. At present, it is unclear which biologics are more superior. This study performed a systematic review and meta-analysis to assess the risk of adverse pregnancy outcomes in women with Crohn's disease after exposure to biologics. Bibliographic databases were searched from inception to May 2021. The outcomes of interest were preterm delivery, low birth weight, spontaneous abortion, and congenital abnormalities. A total of 11 studies comprised of 1,875 pregnancies among women with Crohn's disease were included. Of these, 1,162 received biologics and 713 received non-biologic therapy. During the remission phase of the disease, the use of biological therapy increased the risk of adverse pregnancy outcomes, of which anti-integrins were associated with a higher incidence of adverse pregnancy outcomes than anti-TNF and anti-interleukins. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42020191275.
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Affiliation(s)
- Han Wang
- Department of Gynecology and Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Fang Chen
- Department of Gastroenterology, Hangzhou Red Cross Hospital, Hangzhou, China
| | - Yue Hu
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
| | - Mengdie Shen
- Department of Internal Medicine, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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14
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Kushner T, Fairchild A, Johnson FR, Sands BE, Mahadevan U, Subramanian S, Ananthakrishnan A, Ha C, Bewtra M. Women's Willingness to Accept Risks of Medication for Inflammatory Bowel Disease During Pregnancy. PATIENT-PATIENT CENTERED OUTCOMES RESEARCH 2021; 15:353-365. [PMID: 34750784 DOI: 10.1007/s40271-021-00561-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/18/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Women with inflammatory bowel disease (IBD) face difficult decisions regarding treatment during pregnancy: while the majority of IBD medications are safe, there is substantial societal pressure to avoid exposures during pregnancy. However, discontinuation of IBD medications risks a disease flare occurring during pregnancy. OBJECTIVE This study quantified women's knowledge about pregnancy and IBD and their willingness to accept the risks of adverse pregnancy outcomes to avoid disease activity or medication use during pregnancy. METHODS Women with IBD recruited from four centers completed an online discrete-choice experiment stated-preference study including eight choice tasks and the Crohn's and Colitis Pregnancy Knowledge questionnaire. Random-parameters logit was used to estimate preferences for both the respondent personally and what the respondent thought most women would prefer. We also tested for systematically different preferences among individuals with different demographic and personal characteristics, including IBD knowledge. The primary outcome was the maximum acceptable risk of premature birth, birth defects, or miscarriage that women with IBD were willing to accept to avoid (1) taking an IBD medication or (2) having a disease flare during pregnancy. RESULTS Among 230 respondents, women would accept, on average, up to a 4.9% chance of miscarriage to avoid a disease flare. On average, there were no statistically significant differences in women's preferences for continuing versus avoiding medication in the absence of a flare. However, prior understanding of IBD and pregnancy significantly affected preferences for IBD medication use during pregnancy: women with "poor knowledge" would accept up to a 6.4% chance of miscarriage to avoid IBD medication use during pregnancy, whereas women with "adequate knowledge" would accept up to a 5.1% chance of miscarriage in order to remain on their medication. Respondents' personal treatment preferences did not differ from their assessment of other women's preferences. CONCLUSIONS Women with IBD demonstrated a strong preference for avoiding disease activity during pregnancy. Knowledge regarding pregnancy and IBD was a strong modifier of preferences for continuation of IBD medications during pregnancy. These findings point to an important opportunity for intervention to improve disease control through education to increase medication adherence and alleviate unnecessary fears about IBD medication use during pregnancy.
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Affiliation(s)
- Tatyana Kushner
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - F Reed Johnson
- Duke Clinical Research Institute, Duke University, Durham, NC, USA
| | - Bruce E Sands
- Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | | | | | - Christina Ha
- Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Meenakshi Bewtra
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA. .,Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, 724 Blockley Hall, 423 Guardian Dr, Philadelphia, PA, 19104, USA. .,Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
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15
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De Felice KM, Kane S. Safety of anti-TNF agents in pregnancy. J Allergy Clin Immunol 2021; 148:661-667. [PMID: 34489011 DOI: 10.1016/j.jaci.2021.07.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 07/02/2021] [Accepted: 07/06/2021] [Indexed: 02/07/2023]
Abstract
Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis are associated with adverse pregnancy outcomes. Active maternal disease during pregnancy is associated with additional negative outcomes. Anti-TNF agents are effective treatments for inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. These agents cross the placenta starting in the second trimester, with levels detected for several months after birth. This has led to safety concerns, with continued therapy during pregnancy for both the mother and the infant. This review covers retrospective and prospective data published from various cohorts of pregnant women exposed to anti-TNF agents during pregnancy. It highlights the safety of anti-TNF drugs in pregnancy, breast-feeding, and during the first year of life of the infant.
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Affiliation(s)
- Kara M De Felice
- Department of Gastroenterology, Louisiana State University, Department of Gastroenterology, New Orleans, La.
| | - Sunanda Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minn
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16
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El Miedany Y, Palmer D. Rheumatology-led pregnancy clinic: men perspective. Clin Rheumatol 2021; 40:3067-3077. [PMID: 33449229 PMCID: PMC8289755 DOI: 10.1007/s10067-020-05551-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 12/12/2020] [Accepted: 12/14/2020] [Indexed: 10/26/2022]
Abstract
The birth of reproductive rheumatology as a subject of interest in rheumatology has led to improvement of clinical care for patients living with autoimmune rheumatic diseases and paved the way towards setting a specialized pregnancy service within the standard rheumatology practice. In contrast to women, where there has been wealth of literature regarding pregnancy, lactation, and birth outcomes, there is not as much focusing on male sexual health and outcomes among inflammatory arthritis patients. Challenges such as decrease ability to conceive, impaired fertility, erectile dysfunction, and other sexual problems have been raised by male patients living with autoimmune rheumatic diseases. This broad scope gives the reproductive health concept in men another expansion with views to include sexual health problems screening among men attending the standard outpatient rheumatology clinics. This article adds to the paucity of real-life experience and aims at discussing the sexual health from the men perspective and provides a practical approach towards screening, and assessment of men living with autoimmune diseases in standard day to day practice.
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Affiliation(s)
| | - Deborah Palmer
- Rheumatology Department, North Middlesex University Hospital, London, England
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17
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Shen X, Wan Q, Zhao R, Wu Y, Wang Y, Cui Y, Su X, Wu X. Inflammatory bowel diseases and the risk of adverse health outcomes: Umbrella review of meta-analyses of observational studies. Dig Liver Dis 2021; 53:809-816. [PMID: 33551353 DOI: 10.1016/j.dld.2021.01.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 01/17/2021] [Accepted: 01/21/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Accumulating evidence indicates a plausible association between inflammatory bowel diseases and the risk of adverse health outcomes. However, the conclusions are inconsistent. We aimed to perform an umbrella review of meta-analyses to appraise and grade the evidence of the association between inflammatory bowel diseases and the risk of adverse health outcomes. METHODS Meta-analyses of observational studies that examined the associations between inflammatory bowel disease and the risk of adverse health outcomes in PubMed, EMBASE, and Web of Science were screened. RESULTS This umbrella review identified 25 meta-analyses, which yielded 123 effect estimates for 60 unique putative health outcomes. Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes, including multiple cancers, cardiovascular disease, adverse pregnancy outcomes, adverse oral outcomes, and other adverse events. Moreover, inflammatory bowel diseases caused greater harm to health based on the presented evidence. However, none of the evidence was classified as "high" quality, only 15% was classified as "moderate," and 65% of outcomes were rated as "very low." CONCLUSION Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes and further studies should be conducted to draw firmer conclusions.
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Affiliation(s)
- Xiaoding Shen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Qianyi Wan
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Rui Zhao
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yutao Wu
- West China School of Stomatology, Sichuan University, Chengdu 610041, China
| | - Yong Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yaping Cui
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xiangnan Su
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xiaoting Wu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
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Guerrero Vinsard D, Kane SV. Biologics and pregnancy: a clinician's guide to the management of IBD in pregnant women. Expert Rev Gastroenterol Hepatol 2021; 15:633-641. [PMID: 33440996 DOI: 10.1080/17474124.2021.1876562] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 01/12/2021] [Indexed: 10/22/2022]
Abstract
Introduction: Women with inflammatory bowel disease (IBD) endorse a tremendous amount of concern about medication exposure during pregnancy and their effects on the fetus. Medical providers caring for this patient population should be well informed and feel comfortable counseling their patients for the best pregnancy outcome possible.Areas covered: It is of particular importance to understand the implications of use of biologics in preconception, pregnancy, and postpartum timeframes. Herein, we aim to inform the clinician about the impact of uncontrolled inflammation during pregnancy, the mechanisms of biologic transport through the placenta, the effects of biologics in maternal and neonatal outcomes, and additional postpartum considerations such as breastfeeding and vaccination safety.Expert opinion: The groundwork already set by previous research in terms of safety of biologic therapy during pregnancy has been reassuring. With the advent of more mechanisms of action but similar protein structure, i.e. they are IgG1 antibodies; the authors anticipate the recommendation of continuation of therapy throughout pregnancy will be sustained.
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Affiliation(s)
| | - Sunanda V Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, USA
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19
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The positive effect of pregnancy in rheumatoid arthritis and the use of medications for the management of rheumatoid arthritis during pregnancy. Inflammopharmacology 2021; 29:987-1000. [PMID: 33844107 DOI: 10.1007/s10787-021-00808-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 03/30/2021] [Indexed: 01/30/2023]
Abstract
Rheumatoid arthritis (RA) is an autoimmune systemic inflammatory disorder that is mostly characterised by progressive symmetrical joint destruction, particularly in the wrist and fingers, while it may also affect additional joints and several organs, such as the skin, heart, blood vessels, and lungs. It is identified by raised anti-rheumatoid factor and anti-cyclic citrullinated peptide antibodies. The chemical mediators involved in the activity of RA are IL-1β, TNF-α, and IL-6. Pregnancy exerts a positive effect on RA that helps to modulate the disease condition. Different hypotheses are recommended to explain the ameliorating effect of pregnancy in RA. RA cannot be completely cured. The treatment goal is the attrition of pain and inflammation and the further progression of the disease. Long-term management of RA is carried out using disease-modifying antirheumatic drugs (DMARDs). Therapy of acute flares can be done with Non-steroidal anti-inflammatory drugs (NSAIDs) accompanied by ad interim usage of glucocorticoids. Biologic response modifiers are also available; they act by abolishing the activity of T- cells. However, it is necessary to select the correct treatment regimen when it comes to the management of RA in pregnancy.
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20
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Romanowska-Próchnicka K, Felis-Giemza A, Olesińska M, Wojdasiewicz P, Paradowska-Gorycka A, Szukiewicz D. The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding. Int J Mol Sci 2021; 22:ijms22062922. [PMID: 33805757 PMCID: PMC7998738 DOI: 10.3390/ijms22062922] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 03/11/2021] [Indexed: 12/15/2022] Open
Abstract
Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.
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Affiliation(s)
- Katarzyna Romanowska-Próchnicka
- Department of Biophysics and Human Physiology, Faculty of Health Sciences, Warsaw Medical University, 02-091 Warsaw, Poland; (K.R.-P.); (P.W.); (D.S.)
- Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland;
| | - Anna Felis-Giemza
- Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland;
- Correspondence:
| | - Marzena Olesińska
- Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland;
| | - Piotr Wojdasiewicz
- Department of Biophysics and Human Physiology, Faculty of Health Sciences, Warsaw Medical University, 02-091 Warsaw, Poland; (K.R.-P.); (P.W.); (D.S.)
| | - Agnieszka Paradowska-Gorycka
- Department of Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, 02-637 Warsaw, Poland;
| | - Dariusz Szukiewicz
- Department of Biophysics and Human Physiology, Faculty of Health Sciences, Warsaw Medical University, 02-091 Warsaw, Poland; (K.R.-P.); (P.W.); (D.S.)
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21
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Cao RH, Grimm MC. Pregnancy and medications in inflammatory bowel disease. Obstet Med 2021; 14:4-11. [PMID: 33995565 PMCID: PMC8107959 DOI: 10.1177/1753495x20919214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2019] [Revised: 01/20/2020] [Accepted: 02/21/2020] [Indexed: 12/27/2022] Open
Abstract
Inflammatory bowel disease (IBD) affects patients at a significant time in their lives, often coinciding with family planning or pregnancy. While advances in IBD therapies have afforded women greater opportunities for successful conception and pregnancy outcomes, there still remains considerable maternal fear surrounding continuation of treatment in pregnancy. With the exception of methotrexate, most IBD drugs are safe and well tolerated during pregnancy and are not associated with significant risk of adverse fetal or pregnancy outcomes. Furthermore, the current evidence overwhelmingly suggests that good control of disease activity and clinical remission at time of conception are the greatest prognostic factors for an uncomplicated pregnancy and maintenance of quiescent disease. Management of pregnant women with IBD should involve discussions with the mother and family about fears or concerns surrounding the impact of IBD on pregnancy. Mothers should be supported and counselled carefully on the safety and importance of adherence to therapy in maintaining remission. Optimal management of these women requires an inter-disciplinary team effort, involving the general practitioner, in close consultation with both gastroenterologists and obstetricians.
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Affiliation(s)
- Rena H Cao
- St George and Sutherland Clinical School,
University of New South Wales, Sydney, Australia
| | - Michael C Grimm
- St George and Sutherland Clinical School,
University of New South Wales, Sydney, Australia
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22
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Beltagy A, Aghamajidi A, Trespidi L, Ossola W, Meroni PL. Biologics During Pregnancy and Breastfeeding Among Women With Rheumatic Diseases: Safety Clinical Evidence on the Road. Front Pharmacol 2021; 12:621247. [PMID: 34122062 PMCID: PMC8189556 DOI: 10.3389/fphar.2021.621247] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 01/04/2021] [Indexed: 12/31/2022] Open
Abstract
Females are generally more affected by autoimmune diseases, a fact that underlines the relationship with pregnancy and the safety of anti-rheumatic drugs in pregnancy and lactation. Biologic therapies are increasingly prescribed to treat and maintain remission in a significant number of systemic autoimmune rheumatic diseases. The experience with the use of biologics during gestation is extremely lacking because of the observational nature of the available studies and the difficulty in designing proper clinical trials in pregnancy. Among the studied biologics, more information was published on TNFα inhibitors and, in particular, on their potential passage through the placenta and impact on the fetus. Currently, a fragment of anti-TNFα monoclonal IgG, certolizumab pegol, is considered safe with almost no placental transfer. Subsequent observations are suggesting a comparable safety for the soluble TNFα receptor etanercept. Another biologic, eculizumab, the anti-C5a antibody used to treat complement-mediated microangiopathies, is also considered safe due to the unique engineered IgG2/4κ formulation that limits its passage through the placental barrier. Still, long-term data about children born to women treated with biologics in pregnancy are not attainable. Data on breastfeeding are currently available for several biologics. This article reviews the literature available about which drugs are considered safe during pregnancy and lactation, which are not, and on future prospects.
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Affiliation(s)
- Asmaa Beltagy
- Istituto Auxologico Italiano, IRCCS, Immunorheumatology Research Laboratory, Milan, Italy.,Rheumatology and Clinical Immunology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Azin Aghamajidi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Laura Trespidi
- Department of Obstetrics and Gynaecology, Fondazione Ca Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Wally Ossola
- Department of Obstetrics and Gynaecology, Fondazione Ca Granda, Ospedale Maggiore Policlinico, Milan, Italy
| | - Pier Luigi Meroni
- Istituto Auxologico Italiano, IRCCS, Immunorheumatology Research Laboratory, Milan, Italy
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Ali MF, He H, Friedel D. Inflammatory bowel disease and pregnancy: fertility, complications and treatment. Ann Gastroenterol 2020; 33:579-590. [PMID: 33162735 PMCID: PMC7599341 DOI: 10.20524/aog.2020.0536] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 07/27/2020] [Indexed: 12/30/2022] Open
Abstract
Inflammatory bowel disease (IBD) is commonly diagnosed and treated in the young population. Therefore, it is common that women anticipating or undergoing pregnancy will have to cope with the additional burden of their IBD. Pregnancy in an IBD patient also presents challenges for the practitioner, in that the usual diagnostic and therapeutic armamentarium of potential tests and therapies is disrupted. This review covers the implications of IBD for fertility, pregnancy and offspring, and discusses the management of IBD in pregnancy.
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Affiliation(s)
- Mohammad Fahad Ali
- Department of Gastroenterology and Hepatology, Guthrie Cortland Medical Center (Mohammad Fahad Ali)
| | - Harry He
- Department of Medicine, NYU Winthrop University Hospital (Harry He)
| | - David Friedel
- Department of Gastroenterology, NYU Winthrop University Hospital (David Friedel), USA
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Geldhof A, Slater J, Clark M, Chandran U, Coppola D. Exposure to Infliximab During Pregnancy: Post-Marketing Experience. Drug Saf 2020; 43:147-161. [PMID: 31677004 PMCID: PMC7007430 DOI: 10.1007/s40264-019-00881-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background Women of childbearing potential are often treated with monoclonal antibodies to control chronic and debilitating inflammatory diseases. Remicade® (innovator infliximab [IFX]) may cross the placenta after the first trimester of pregnancy. Hence, evidence is needed to optimize treatment while carefully weighing benefits and risks to the mother and child. Here, we report on birth and infant outcomes (up to 2 years) following gestational exposure to IFX based on a summary of cumulative pregnancy reports in women exposed to IFX during pregnancy from the Janssen global safety database. Methods Prospective and medically confirmed safety data on IFX-exposed pregnancies from Janssen’s global safety surveillance database since authorization in 1998 are summarized. Descriptive statistics were used to summarize pregnancy and infant outcomes overall, by disease and timing of exposure. Results As of 23 August 2018, 1850 maternally IFX-exposed pregnancies with known outcomes were identified from the safety database. Of the 1850 pregnancies (mean age 29.7 years), 1526 (82.5%) resulted in live births. When reported, most women had Crohn’s disease (67.7%) or ulcerative colitis (18.4%), and 82.8% of live births were exposed to IFX in the first trimester. Spontaneous abortion/intrauterine death/ectopic pregnancy/molar pregnancy (12.1%), preterm births (9.2%), low birth weight infants (3.6%), congenital anomalies (2.0%), and infant infections (1.2%) were documented. The type of congenital anomalies and frequency of serious infant infections observed were consistent with the general population. Frequencies of congenital anomalies and other adverse outcomes were similar in women exposed to IFX in the first trimester and those exposed in the third trimester. More preterm births (13–18.8%) and infant complications (8.7–12.5%) were reported with concomitant immunosuppressant use. Conclusions The observed prevalence of adverse pregnancy and infant outcomes including congenital anomalies following exposure to IFX did not exceed estimates reported for the general population and no unexpected patterns were observed.
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Affiliation(s)
- Anja Geldhof
- Janssen Biologics B.V., Medical Affairs, Einsteinweg 101, 2333, Leiden, CB, The Netherlands.
| | | | - Michael Clark
- Janssen Research and Development, Spring House, PA, USA
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25
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Uyaroglu OA, Seyhoglu E, Erden A, Kilic L, Karadag O, Akdogan A, Bilgen SA, Ertenli AI, Kiraz S, Kalyoncu U. Pregnancy outcomes in partners of male ankylosing spondylitis patients treated with anti-tumour necrosis factor-α biologics: real-life results from a single-centre cross-sectional study. Rheumatol Int 2020; 40:1501-1507. [PMID: 31993731 DOI: 10.1007/s00296-020-04518-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Accepted: 01/16/2020] [Indexed: 10/25/2022]
Abstract
Most patients with inflammatory arthritis are at their reproductive ages. Use of anti-tumour necrosis factor alpha (anti-TNF-α) agents, one of the important treatment options for inflammatory arthritis, can cause foetal morbidity and mortality. While most studies on the effects of anti-TNF-α agents on pregnancy outcomes are about maternal exposure, the number of studies on the risks related to paternal exposure is insufficient. This study aimed to assess pregnancy periods and outcomes of the partners of male ankylosing spondylitis (AS) patients receiving anti-TNF-α treatment during the preconception period. Totally, 163 male AS patients using anti-TNF-α agents were identified from the Hacettepe University Biological Registry. Of these patients, 45 (27.6%) who declared that their partners got pregnant after initiation on anti-TNF-α agents were included. Data regarding demographics and drug exposure and pregnancy and infant outcomes were evaluated. Of 45 pregnancies, 39 (86.7%) resulted in healthy live births, 3 (6.7%) resulted in spontaneous abortion, and 3 (6.7%) were terminated with curettage. Of 39 live births, 34 (87.2%) were term and 5 (12.8%) were preterm, 30 (76.9%) had normal birth weight, 6 (15.4%) had low birth weight, and 3 (7.7%) had fetal macrosomia. No congenital malformations related to paternal exposure were observed. This study is valuable as being one of the studies providing pregnancy outcomes of partners of male AS patients receiving anti-TNF-α agents with its relatively high number of patients. The results suggested that paternal exposure to anti-TNF-α agents during preconception period could be safe on pregnancy outcomes.
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Affiliation(s)
- Oguz Abdullah Uyaroglu
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey.
| | - Emrah Seyhoglu
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Sihhiye, 06100, Ankara, Turkey
| | - Abdulsamet Erden
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Levent Kilic
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Omer Karadag
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ali Akdogan
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Sule Apras Bilgen
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Ali Ihsan Ertenli
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Sedat Kiraz
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
| | - Umut Kalyoncu
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
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A Pharmacological Approach to Managing Inflammatory Bowel Disease During Conception, Pregnancy and Breastfeeding: Biologic and Oral Small Molecule Therapy. Drugs 2019; 79:1053-1063. [PMID: 31183768 DOI: 10.1007/s40265-019-01141-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The inflammatory bowel diseases commonly affect individuals during their peak reproductive years. Patients are often concerned about the impact of medical therapies on their ability to conceive, effect on the fetus, as well as the ability to breastfeed, which has led to poor medical adherence during pregnancy. However, most medications are safe, and discontinuation may lead to active disease, which is associated with adverse materno-fetal outcomes. The anti-TNF biologic therapies, infliximab and adalimumab have been extensively studied in the context of pregnancy. They are actively transferred to the placenta during the second and third trimesters; these have not been associated with an increased rate of congenital abnormalities or fetal death. The minimal amounts of drug that are transferred to breast milk are proteolyzed by the infant's digestive system with no reported short- or long-term adverse effects. There is a paucity of clinical data for the other approved anti-TNF agents or newer anti-integrin (vedolizumab) and anti-interleukin (ustekinumab) therapies used in the management of inflammatory bowel disease; however, no significant safety signals have been documented thus far. The new oral small molecule therapy, tofacitinib is teratogenic in animal models and is contra-indicated in patients attempting pregnancy. It is important that patients, as well as physicians managing patients with these conditions, be aware of the impact of these medical therapies during pregnancy.
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Shannahan SE, Erlich JM, Peppercorn MA. Insights into the treatment of inflammatory bowel disease in pregnancy. Therap Adv Gastroenterol 2019; 12:1756284819852231. [PMID: 31191713 PMCID: PMC6540496 DOI: 10.1177/1756284819852231] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Accepted: 04/17/2019] [Indexed: 02/04/2023] Open
Abstract
Patients diagnosed with inflammatory bowel disease (IBD) are most commonly diagnosed in late adolescence or early adulthood, with half of patients being diagnosed before age 32, thus impacting peak years of reproduction and family planning. While controlled IBD has no negative effects on the ability to conceive, there is overall a trend towards voluntary childlessness due to patients' concerns for adverse fetal outcomes from underlying IBD and from adverse medication effects. Active disease at the time of conception is associated with worsening disease activity during pregnancy and carries a higher risk of poor fetal outcomes. It is therefore important to maintain remission during pregnancy, which is often achieved with pharmacologic therapy. The goal of this paper is to provide a comprehensive review of the current literature and safety data for pharmacologic treatment of IBD in pregnancy, in breastfeeding women, and in men planning to have children.
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Affiliation(s)
- Sarah E. Shannahan
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Jonathan M. Erlich
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Mark A. Peppercorn
- Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
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28
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Berkhout A, Clark JE, Wen SCH. In utero exposure to biologic disease-modifying anti-rheumatic drugs and effects to the infant: infectious complications, vaccine response, and safety of live vaccine administration. Expert Rev Vaccines 2019; 18:495-504. [PMID: 30916600 DOI: 10.1080/14760584.2019.1599286] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Biologic disease-modifying anti-rheumatic drugs (bDMARDS) are increasingly used in clinical practice for a variety of conditions. Due to concerns surrounding persistence of drug levels and resulting immunosuppression, current case reports recommend against live vaccine administration in the first year of life for an infant exposed to perinatal bDMARDS. As a result, this significantly impacts receipt of rotavirus vaccination, a vaccine recommended in many countries' national immunization program. Area covered: We have reviewed all available published literature to explore the effect of peripartum bDMARDS exposure on infant immune responses, safety of live vaccines, and vaccine efficacy in the first year of life. Expert opinion: We recommend that otherwise healthy newborns with a history of perinatal exposure to bDMARDS should receive rotavirus vaccinations as per the recommended schedule. Bacille Calmette et Guerin vaccine should be withheld in the first year of life. No additional booster doses of inactivated vaccines are required as they appear to mount adequate immune responses to the routine schedule.
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Affiliation(s)
- Angela Berkhout
- a Infection Management and Prevention Service, Queensland Children's Hospital , University of Queensland , Brisbane , Australia.,b The Queensland Children's Hospital , Brisbane , Australia
| | - Julia E Clark
- a Infection Management and Prevention Service, Queensland Children's Hospital , University of Queensland , Brisbane , Australia.,b The Queensland Children's Hospital , Brisbane , Australia
| | - Sophie Chien-Hui Wen
- a Infection Management and Prevention Service, Queensland Children's Hospital , University of Queensland , Brisbane , Australia.,b The Queensland Children's Hospital , Brisbane , Australia
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Mahadevan U, Robinson C, Bernasko N, Boland B, Chambers C, Dubinsky M, Friedman S, Kane S, Manthey J, Sauberan J, Stone J, Jain R. Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology 2019; 156:1508-1524. [PMID: 30658060 DOI: 10.1053/j.gastro.2018.12.022] [Citation(s) in RCA: 218] [Impact Index Per Article: 36.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Uma Mahadevan
- University of California, San Francisco, San Francisco, California
| | - Christopher Robinson
- Bon Secours St Francis and Summerville Medical Center, Charleston, South Carolina
| | - Nana Bernasko
- Penn State Health, Milton S. Hershey Medical Center, Hershey, Pennsylvania
| | | | | | - Marla Dubinsky
- Icahn School of Medicine at Mount Sinai, New York, New York
| | | | | | - Jacob Manthey
- American Gastroenterological Association, Bethesda, Maryland
| | - Jason Sauberan
- Sharp Neonatal Research Institute, San Diego, California
| | - Joanne Stone
- Icahn School of Medicine at Mount Sinai, New York, New York
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30
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Mahadevan U, Robinson C, Bernasko N, Boland B, Chambers C, Dubinsky M, Friedman S, Kane S, Manthey J, Sauberan J, Stone J, Jain R. Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group. Am J Obstet Gynecol 2019; 220:308-323. [PMID: 30948039 DOI: 10.1016/j.ajog.2019.02.027] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Uma Mahadevan
- University of California, San Francisco, San Francisco, California
| | - Christopher Robinson
- Bon Secours St Francis and Summerville Medical Center, Charleston, South Carolina
| | - Nana Bernasko
- Penn State Health, Milton S. Hershey Medical Center, Hershey, Pennsylvania
| | | | | | - Marla Dubinsky
- Icahn School of Medicine at Mount Sinai, New York, New York
| | | | | | - Jacob Manthey
- American Gastroenterological Association, Bethesda, Maryland
| | - Jason Sauberan
- Sharp Neonatal Research Institute, San Diego, California
| | - Joanne Stone
- Icahn School of Medicine at Mount Sinai, New York, New York
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31
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Safety of anti-rheumatic drugs in men trying to conceive: A systematic review and analysis of published evidence. Semin Arthritis Rheum 2019; 48:911-920. [DOI: 10.1016/j.semarthrit.2018.07.011] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 05/18/2018] [Accepted: 07/23/2018] [Indexed: 12/31/2022]
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32
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Park YE, Kim TO. Sexual Dysfunction and Fertility Problems in Men with Inflammatory Bowel Disease. World J Mens Health 2019; 38:285-297. [PMID: 30929327 PMCID: PMC7308231 DOI: 10.5534/wjmh.190007] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2019] [Revised: 01/29/2019] [Accepted: 02/10/2019] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that is usually diagnosed in young individuals. Crohn's disease and ulcerative colitis are the 2 principal forms of IBD. Patients with IBD demonstrate varying degrees of disease activity and sometimes need to undergo bowel surgery such as proctocolectomy with ileal pouch-anal anastomosis that involves removal of the entire colon and rectum with consequent sexual dysfunction. Several studies have shown that sulfasalazine, affects male fertility. Additionally, many men with IBD are unable to control their smoking, drinking, and eating habits, which can cause worsening of disease activity and fertility. Therefore, infertility and sexual dysfunction are important issues in young patients diagnosed with IBD because they are related to optimal management of the disease and patients' quality of life. Only a few studies have reported sexual dysfunction and infertility in men with IBD. Therefore, this study reviewed the current literature describing male sexual dysfunction scales and evaluated the causes of sexual dysfunction and infertility in men with IBD.
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Affiliation(s)
- Yong Eun Park
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Tae Oh Kim
- Division of Gastroenterology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.
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33
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Mahadevan U, Robinson C, Bernasko N, Boland B, Chambers C, Dubinsky M, Friedman S, Kane S, Manthey J, Sauberan J, Stone J, Jain R. Inflammatory Bowel Disease in Pregnancy Clinical Care Pathway: A Report From the American Gastroenterological Association IBD Parenthood Project Working Group. Inflamm Bowel Dis 2019; 25:627-641. [PMID: 30821832 DOI: 10.1093/ibd/izz037] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Indexed: 12/11/2022]
Affiliation(s)
- Uma Mahadevan
- University of California, San Francisco, San Francisco, California
| | - Christopher Robinson
- Bon Secours St Francis and Summerville Medical Center, Charleston, South Carolina
| | - Nana Bernasko
- Penn State Health, Milton S. Hershey Medical Center, Hershey, Pennsylvania
| | | | | | - Marla Dubinsky
- Icahn School of Medicine at Mount Sinai, New York, New York
| | | | | | - Jacob Manthey
- American Gastroenterological Association, Bethesda, Maryland
| | - Jason Sauberan
- Sharp Neonatal Research Institute, San Diego, California
| | - Joanne Stone
- Icahn School of Medicine at Mount Sinai, New York, New York
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34
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Lee KE, Jung SA, Park SH, Moon CM, Shim SY, Kim ES, Cho SJ, Kim SE, Cho KB, Yang SK. Influence of anti-tumor necrosis factor-alpha therapy to pregnant inflammatory bowel disease women and their children's immunity. Intest Res 2019; 17:237-243. [PMID: 30727711 PMCID: PMC6505087 DOI: 10.5217/ir.2018.00071] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 11/17/2018] [Indexed: 12/11/2022] Open
Abstract
Background/Aims The onset of inflammatory bowel disease (IBD) usually occurs at young age, and therefore, women IBD patients experience pregnancy during their disease progression. Recently, the use of anti-tumor necrosis factor-α (anti-TNF-α) has been rapidly increasing. The aim of this study was to evaluate pregnancy related outcomes in women with IBD who were treated with anti-TNF-α during pregnancy and immunity of their children. Methods Korean women with IBD who had been treated with anti-TNF-α during pregnancy had been enrolled. Medical records were reviewed and a survey was performed for each patient. For the patients who agreed on additional examination for their children, children’s growth, medical history and antibody to hepatitis B surface antigen (anti-HBs) titer were checked. Results All 18 patients had been diagnosed with Crohn’s disease. There was not any case of preterm delivery, low birth-weight infant, congenital anomaly, nor stillbirth. All 12 children had followed the regular vaccination schedule for hepatitis B and 4 of them showed negative results for anti-HBs. After the 1 booster vaccination, all children demonstrated seroconversion. Regarding live vaccines, 4 children had bacillus Calmette-Guerin and 4 had rotavirus vaccine before 6 months, without any specific side effects. Conclusions This was the first study of immunity of the children born from IBD women who had been treated with anti-TNF-α medication during their pregnancy. IBD women had comparable pregnancy outcomes with the general women population, suggesting that the disease activity rather than the administered medication would be more important in healthy pregnancy. Considering the history of vaccination and anti-HBs titers, immunity seems to be intact in the children.
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Affiliation(s)
- Ko Eun Lee
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Sung-Ae Jung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea
| | - Chang Mo Moon
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - So Yeon Shim
- Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.,Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Su Jin Cho
- Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Korea
| | - Seong-Eun Kim
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Kwang Bum Cho
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, Korea
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35
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Pham-Huy A, Sadarangani M, Huang V, Ostensen M, Castillo E, Troster SM, Vaudry W, Nguyen GC, Top KA. From mother to baby: antenatal exposure to monoclonal antibody biologics. Expert Rev Clin Immunol 2019; 15:221-229. [PMID: 30570400 DOI: 10.1080/1744666x.2019.1561282] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION More women with autoimmune and inflammatory conditions are being treated with monoclonal antibody biologics (mAbs) during their pregnancy, to maintain clinical remission. The use of anti-tumor necrosis factor alpha agents in pregnancy appears to be safe but less is known regarding other mAbs, such as anti-integrins and anti-cytokine agents. There are currently no comprehensive guidelines on how to manage the exposed infants. Areas covered: We review recent literature to assess the impact of mAbs on birth and early infant outcomes, including what is currently known about maternal and infant drug levels at birth and drug clearance in the infant. We describe the potential risks of infections and reported hematological and immunological effects of antenatal mAbs exposure on the infant and provide guidance on the management of the exposed infant. Expert opinion: Exposed infants should be monitored closely. Certain mAb exposures require specific testing and management. Safety monitoring should be done in a multidisciplinary approach and should include pediatric care providers. The current clinical experience with anti-tumor necrosis factor agents in pregnancy cannot be extrapolated to other mAbs. Long-term observational studies and a multicenter international registry are needed to better appreciate the impact of exposure, especially to newer mAbs.
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Affiliation(s)
- Anne Pham-Huy
- a Department of Pediatrics, Division of Infectious Diseases , Children's Hospital of Eastern Ontario, University of Ottawa , Ottawa , ON , Canada
| | - Manish Sadarangani
- b Vaccine Evaluation Center , BC Children's Hospital Research Institute, University of British Columbia , Vancouver , BC , Canada
| | - Vivian Huang
- c Division of Gastroenterology , Mount Sinai Hospital, University of Toronto , Toronto , ON , Canada
| | - Monika Ostensen
- d Norwegian National Advisory Unit on Pregnancy and Rheumatic Diseases, Department of Rheumatology , St. Olavs University Hospital , Trondheim , Norway.,e Department of Rheumatology , Sørlandet Sykehus , Kristiansand , Norway
| | - Eliana Castillo
- f Departments of Medicine and Obstetrics and Gyneacology , Cumming School of Medicine , Calgary , AB , Canada
| | - Sarah M Troster
- g Division of Rheumatology , University of Alberta , Edmonton , AB , Canada
| | - Wendy Vaudry
- h Division of infectious Diseases, Department of Pediatrics , University of Alberta, Stollery Children's Hospital , Edmonton , AB , Canada
| | - Geoffrey C Nguyen
- c Division of Gastroenterology , Mount Sinai Hospital, University of Toronto , Toronto , ON , Canada
| | - Karina A Top
- i Departments of Pediatrics and Community Health & Epidemiology , Dalhousie University , Halifax , NS , Canada
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Moens A, van Hoeve K, Humblet E, Rahier JF, Bossuyt P, Dewit S, Franchimont D, Macken E, Nijs J, Posen A, Strubbe B, Van Hootegem A, Van Moerkercke W, Vermeire S, Ferrante M. Outcome of Pregnancies in Female Patients With Inflammatory Bowel Diseases Treated With Vedolizumab. J Crohns Colitis 2019; 13:12-18. [PMID: 30281093 DOI: 10.1093/ecco-jcc/jjy142] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS Vedolizumab is an IgG1 anti-α4β7 integrin antibody approved for the treatment of inflammatory bowel diseases [IBD], but without clear safety data during conception, pregnancy and nursing. Animal studies showed that mucosal vascular addressin cell adhesion molecule 1 [MAdCAM-1] is expressed by maternal vessels in the placenta and recruits α4β7-expressing cells that are considered important for maternal/fetal tolerance. Blocking this interaction by vedolizumab might affect this process. We aimed to evaluate pregnancy outcomes in vedolizumab-treated female IBD patients. METHODS We conducted a retrospective, multicentre Belgian observational study. Details on disease activity, prenatal complications, delivery and neonatal outcome were collected through a case report form. RESULTS Twenty-four pregnancies were reported. Five women had active disease at conception and one patient flared during pregnancy. There were 23 live births. Complications were observed in 25% of pregnancies [premature rupture of membranes, pre-eclampsia, miscarriage, elective termination and stillbirth] and in 35% of infants [prematurity, intra-uterine growth retardation, small for gestational age and congenital malformations including hip dysplasia, pulmonary valve stenosis and Hirschprung's disease]. Vedolizumab was continued throughout pregnancy in two females and stopped in the 1st and 2nd trimester in five and 16 patients, respectively. For live born children, the median [interquartile range] gestational age, weight and Apgar score 5 min after birth were 39 [37-39.6] weeks, 3270 [3080-3585] grams and 10 [9-10], respectively. CONCLUSIONS Although several complications were observed, both in mothers and in newborns, no firm conclusions can be drawn. Awaiting prospective and controlled registries, vigilance and strict follow-up of pregnant patients treated with vedolizumab seems mandatory.
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Affiliation(s)
- Annick Moens
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.,Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Karen van Hoeve
- Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.,Department of Paediatric Gastroenterology, University Hospitals Leuven, KU Leuven, Leuven, Belgium
| | - Evelien Humblet
- Department of Gastroenterology, Ziekenhuis Oost-Limburg - Campus Sint-Jan, Genk, Belgium
| | - Jean-François Rahier
- Deparment of Gastroenterology, CHU UCL Namur, Université catholique de Louvain, Yvoir, Belgium
| | - Peter Bossuyt
- Department of Gastroenterology, Imeldaziekenhuis, Bonheiden, Belgium
| | - Sophie Dewit
- Department of Gastroenterology, Mariaziekenhuis Noord-Limburg, Overpelt, Belgium
| | - Denis Franchimont
- Department of Gastroenterology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Elisabeth Macken
- Department of Gastroenterology, Universiteit ziekenhuis Antwerpen, UZA, Antwerp, Belgium
| | - Jochen Nijs
- Department of Gastroenterology, Sint-Trudo Ziekenhuis, Sint-Truiden, Belgium
| | - Annelies Posen
- Department of Gastroenterology, AZ Vesalius, Tongeren, Belgium
| | | | | | | | - Séverine Vermeire
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.,Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
| | - Marc Ferrante
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.,Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium
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Pregnancy Outcomes Reported During the 13-Year TREAT Registry: A Descriptive Report. Am J Gastroenterol 2018; 113:1678-1688. [PMID: 30022113 DOI: 10.1038/s41395-018-0202-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 06/08/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVES We described pregnancy outcomes in Crohn's disease (CD) patients enrolled in the TREAT Registry who received infliximab before, or during pregnancy and those not treated with infliximab or any biologic agent. METHODS In the TREAT Registry (1999-2012), pregnancy outcomes were analyzed from maternal and paternal patients exposed to infliximab ≤365 days (gestational exposure), >365 days (pre-gestational exposure) of pregnancy outcome or without infliximab exposure (non-biologic exposed). "Healthy infants" were defined as those with no congenital abnormalities, neonatal complications (e.g., jaundice, prematurity, heart murmur, cortical vision/fine motor delay, cardiac failure, hemophilia, or torticollis), prolonged hospitalization, or those who received no special treatment. Disease activity and concomitant medications were also evaluated. RESULTS Overall, 92.3% (324/351) of pregnancies had known outcomes. The majority of both maternal pregnancies (92.6, 91.2, and 87.8%) and partner outcomes (92.7, 93.8, and 91.7%) resulted in live births of healthy infants across gestational, pre-gestational, and non-biologic exposure groups, respectively. Among these, rates of neonatal complications were low for both maternal (6.2, 7.0, and 8.5%), and partner outcomes (4.9, 0, and 0%) in gestational, pre-gestational, and non-biologic exposure groups, respectively. Among maternal pregnancies, numerically higher rates of spontaneous abortions were observed for the gestational exposure group than for the pre-gestational or non-biologic exposed groups. CONCLUSIONS The clinical condition of infants born to women with gestational infliximab exposure was similar to those without exposure. Although a lower live birth rate was reported among infliximab-exposed women, these patients had more severe CD and were more likely to have been exposed to immunosuppressives.
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38
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Kane S. Trick or TREAT? More Safety Data of Infliximab During Pregnancy. Am J Gastroenterol 2018; 113:1592-1593. [PMID: 30333536 DOI: 10.1038/s41395-018-0372-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 09/11/2018] [Indexed: 12/11/2022]
Abstract
Infliximab was the first FDA approved biologic for the treatment of Crohn's disease. Data for its use before and during pregnancy in both females and males have been increasing over the last decade, but most studies have had fewer than 100 patients and inconsistent comparison to healthy control outcomes. New data from the TREAT Safety Registry have a robust N of female and male patients exposed to infliximab with known birth outcomes from both academic and community settings. There does not appear to be any increase in adverse pregnancy outcomes from this population.
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Affiliation(s)
- Sunanda Kane
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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Silva EFDC, Baima JP, de Barros JR, Renosto FL, de Sibia CDF, Saad-Hossne R, Sassaki LY. Anti-TNF Exposure during Pregnancy in Crohn's Disease Patients. Case Rep Gastroenterol 2018; 12:608-616. [PMID: 30483038 PMCID: PMC6244106 DOI: 10.1159/000493921] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Accepted: 09/17/2018] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD) affects young people of reproductive age. Therefore, a broad discussion is needed about the possible disease effects in pregnancy, as well as the risks of fetal exposure to the medications used, especially biological therapy. This study aimed to describe the management of 4 Crohn's disease patients who received anti-TNF therapy during pregnancy and present a literature review. We reported 4 cases composed of young women who became pregnant while receiving anti-TNF agents. The patients presented a satisfactory response to the clinical treatment and the pregnancies progressed without complications. We did not observe maternal or embryonic toxicity, or unfavorable outcomes. The available data point to inflammatory activity as the main risk factor for unfavorable gestational evolution to date, and showed anti-TNF therapy to be safe during pregnancy and breastfeeding. However, the benefits and risks must be discussed with the patient and management decisions should be taken on an individual basis.
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Affiliation(s)
| | - Júlio Pinheiro Baima
- Medical School, Department of Internal Medicine, São Paulo State University (UNESP), Botucatu, Brazil
| | | | - Fernanda Lofiego Renosto
- Medical School, Department of Internal Medicine, São Paulo State University (UNESP), Botucatu, Brazil
| | | | - Rogério Saad-Hossne
- Medical School, Department of Surgery, São Paulo State University (UNESP), Botucatu, Brazil
| | - Ligia Yukie Sassaki
- Medical School, Department of Internal Medicine, São Paulo State University (UNESP), Botucatu, Brazil
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Sandborn WJ, Rutgeerts P, Gasink C, Jacobstein D, Zou B, Johanns J, Sands BE, Hanauer SB, Targan S, Ghosh S, de Villiers WJS, Colombel J, Feagan BG. Long-term efficacy and safety of ustekinumab for Crohn's disease through the second year of therapy. Aliment Pharmacol Ther 2018; 48:65-77. [PMID: 29797519 PMCID: PMC6032827 DOI: 10.1111/apt.14794] [Citation(s) in RCA: 130] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Revised: 02/21/2018] [Accepted: 04/16/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported. METHODS UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients. Dose-adjustment to 90 mg every 8 weeks occurred in patients randomised to 90 mg every 12 weeks and placebo patients with loss of response (Weeks 8-32). All Week 44 completers could enter the long-term extension without further dose adjustment. Placebo patients discontinued following study unblinding. RESULTS A total of 718 patients (all treated) entered the long-term extension (298 randomised and 420 not randomised). Overall, 86.5% (621/718) completed Week 96. The proportions of randomised patients in clinical remission were generally maintained from Week 44 through 92 in ustekinumab 90 mg every 12 weeks (77.4% to 72.6%), every 8 weeks (84.1% to 74.4%), and prior dose adjustment groups (63.4% to 53.5%). At Week 92, the proportions of patients in clinical remission were similar in the ustekinumab 90 mg every 12 weeks and every 8 weeks groups and lower in patients with prior dose adjustment. Proportions of patients in clinical remission at Week 92 for all treated every 8 weeks (64.4%) and every 12 weeks (64.3%) groups were lower than randomised every 8 weeks (74.4%) and every 12 weeks (72.6%) groups, but similarly maintained. Safety events (per hundred patient-years) were similar among all placebo and ustekinumab patients (Week 0-96), including adverse events (484.39 vs 447.76), serious adverse events (19.24 vs 18.82), and serious infections (4.09 vs 4.02). No dose effect was observed. CONCLUSIONS Subcutaneous ustekinumab maintained clinical response and remission through Week 92. No new safety signals were observed. ClinicalTrials.gov number NCT01369355.
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Theodoraki E, Orfanoudaki E, Foteinogiannopoulou K, Koutroubakis IE. Asymptomatic hyperCKemia During Infliximab Therapy in Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis 2018; 24:1266-1271. [PMID: 29718260 DOI: 10.1093/ibd/izy088] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Both muscle-related complaints and elevated serum creatine kinase (CK) levels have been reported in patients with inflammatory bowel disease (IBD) treated with infliximab (IFX), mainly as case reports. The aim of this study was to investigate the effect of IFX therapy on serum CK levels in a cohort of Greek IBD patients. METHODS Demographic, clinical (including muscle complaints), and laboratory data of consecutive IBD patients undergoing IFX treatment and a matched control group of IBD patients without any use of biological treatment were retrospectively analyzed. In both groups, patients having at least 3 CK measurements, with at least 10 days' interval among them, were included. RESULTS The IFX-treated IBD patient group included 82 individuals (75.6% Crohn's Disease [CD]; mean age, 44.7 ± 13.3 years; 60.9% men; median [interquartile range {IQR}] duration of IFX treatment, 27 [12-84] months). Eighty-two patients without treatment with any biological agent formed the control group (62.2% CD; mean age, 50.4 ± 16.4 years; 59.8% men). Twenty-five IFX-treated patients (30.5%) had elevated mean serum CK levels (>180 U/L), compared with 9 (11%) in the control group (P = 0.0003). The median CK value in the IFX group (123.5 U/L; IQR, 91-190.75) was significantly higher than that of the control group (81 U/L; IQR, 57-112.75; P < 0.0001). In the logistic regression analysis, the presence of hyperCKemia was independently correlated with the use of IFX (odds ratio, 4.03; IQR, 1.64-9.90; P = 0.002). No patient with hyperCKemia in both groups reported any persistent symptom of myopathy. CONCLUSIONS More than 30% of IBD patients on IFX present asymptomatic persistent and treatment-related hyperCKemia. Further relevant prospective investigation is needed. 10.1093/ibd/izy088_video1izy088.video15778459427001.
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Affiliation(s)
- Eirini Theodoraki
- Department of Gastroenterology, University Hospital of Heraklion, Greece, Heraklion, Greece
| | - Eleni Orfanoudaki
- Department of Gastroenterology, University Hospital of Heraklion, Greece, Heraklion, Greece
| | | | - Ioannis E Koutroubakis
- Department of Gastroenterology, University Hospital of Heraklion, Greece, Heraklion, Greece
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Kammerlander H, Nielsen J, Kjeldsen J, Knudsen T, Gradel KO, Friedman S, Nørgård BM. Fecal Calprotectin During Pregnancy in Women With Moderate-Severe Inflammatory Bowel Disease. Inflamm Bowel Dis 2018; 24:839-848. [PMID: 29506137 DOI: 10.1093/ibd/izx055] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Fecal calprotectin (FC) is a biomarker used for assessing disease activity among IBD patients. Sparse knowledge exists as to whether FC correlates with clinical disease activity during pregnancy. Our aim was to assess FC and selected biomarkers in women with moderate-severe IBD and correlate them with clinical disease activity scores in pregnant women. METHODS We identified a nationwide cohort of 219 singleton pregnancies in women with moderate-severe disease (all treated with anti-tumor recrosis factor-α [anti-TNF-α] therapy during pregnancy), and we reviewed the medical records to extract clinical details and information on biomarkers. FC, C-reactive protein (CRP), hemoglobin, and albumin were collected according to each trimester. RESULTS A total of 346 FC measurements were obtained throughout the gestational periods. FC values were between 80-120, 259-349, and 778-1277 mg/kg in women with clinically inactive, mild, and moderate-severe disease activity, respectively, and were significantly higher among the women with clinical disease activity. ROC curves for disease activity were computed according to the preconception period: 0.81 (95% confidence interval [CI], 0.69-0.93), first trimester: 0.73 (95% CI, 0.60-0.86), second trimester: 0.74 (95% CI, 0.62-0.86), and third trimester: 0.76 (95% CI, 0.64-0.88), respectively. We found a sensitivity of 69.7%-80.0%, a specificity of 66.7%-73.3%, and a positive predictive value of 66.7%-74.4% over the 4 gestational periods when a cutoff of 200 mg/kg was used. We found no clinically significant differences in CRP, albumin, or hemoglobin. CONCLUSIONS FC in pregnant women with moderate-severe IBD treated with anti-TNF-α therapy was significantly higher in women with clinical disease activity compared with the women without. FC correlated with the level of clinical disease activity in all gestational periods.
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Affiliation(s)
- Heidi Kammerlander
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jan Nielsen
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Jens Kjeldsen
- Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark
| | - Torben Knudsen
- Department of Medical Gastroenterology, Hospital of Southwest Jutland, Esbjerg, Denmark
| | - Kim Oren Gradel
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Sonia Friedman
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.,Crohn's and Colitis Center, Brigham and Women's Hospital, Boston, Massachusetts and Harvard Medical School, Boston, Massachusetts
| | - Bente Mertz Nørgård
- Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.,Crohn's and Colitis Center, Brigham and Women's Hospital, Boston, Massachusetts and Harvard Medical School, Boston, Massachusetts
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Abstract
Pustular psoriasis of pregnancy (PPP) is a life-threatening condition for both the pregnant mother and fetus, and must be efficiently and accurately diagnosed and treated. This condition has historically been classified as a unique, separate dermatosis of pregnancy. However, current opinion and data suggest that it may be a variant of generalized pustular psoriasis. PPP typically occurs in the third trimester and is characterized by widespread coalescent pustules, desquamation, and systemic symptoms. Clinical features and histopathologic evaluation aid in diagnosis. Treatments during pregnancy include high-dose corticosteroids, cyclosporine, narrow-band ultraviolet B radiation, infliximab, granulocyte and monocyte adsorptive apheresis, and systemic antibiotics. Both the mother and fetus should be closely monitored with appropriate laboratory studies for the duration of the pregnancy and postpartum.
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Affiliation(s)
- Megha K Trivedi
- Department of Dermatology, University of California, San Francisco, CA, USA
- Medical School, University of Michigan, Ann Arbor, MI, USA
| | | | - Jenny E Murase
- Department of Dermatology, University of California, San Francisco, CA, USA
- Department of Dermatology, Palo Alto Medical Foundation, Palo Alto, CA, USA
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Fujioka K, Fukushima S, Nishida K, Iijima K, Morioka I. Intraventricular Hemorrhage Due to Coagulopathy After Vitamin K Administration in a Preterm Infant With Maternal Crohn Disease. JAPANESE CLINICAL MEDICINE 2017; 8:1179670717746333. [PMID: 29344001 PMCID: PMC5764135 DOI: 10.1177/1179670717746333] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 10/30/2017] [Indexed: 11/17/2022]
Abstract
Intraventricular hemorrhage (IVH) is a devastating morbidity in preterm infants and can result in poor neurodevelopmental outcomes. Intraventricular hemorrhage usually occurs within 72 hours after birth; post-acute-phase IVH (>1 week after birth) is uncommon. Development of the hemostatic system in fetuses and neonates is an age-dependent evolving process, and the neonatal hemostatic system is characterized by low levels of vitamin K-dependent factors, with further reduction caused by prematurity. Importantly, a severe coagulation deficiency can be a major contributing factor of IVH. Active maternal Crohn disease (CD) during pregnancy causes malnutrition via enteral malabsorption; this may include vitamin K deficiency, resulting in fetal vitamin K deficiency. We herein describe a preterm infant who was born to a mother with CD and developed post-acute-phase IVH due to coagulopathy despite vitamin K administration.
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Affiliation(s)
- Kazumichi Fujioka
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Sachiyo Fukushima
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kosuke Nishida
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kazumoto Iijima
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ichiro Morioka
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
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Anti-TNF-α Use During the Third Trimester of Pregnancy in Women with Moderate-severe Inflammatory Bowel Disease and the Risk of Preterm Birth and Low Birth Weight. Inflamm Bowel Dis 2017; 23:1916-1923. [PMID: 28858070 DOI: 10.1097/mib.0000000000001234] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Little knowledge exists about the association between anti-tumor necrosis factor-alpha (anti-TNF-α) therapy for inflammatory bowel disease during late pregnancy and adverse birth outcomes. We aimed to examine whether treatment with anti-TNF-α during the third trimester affected preterm birth and low birth weight (LBW), compared with women who discontinued anti-TNF-α therapy before the third trimester. METHODS We identified a nationwide cohort of 219 women treated with anti-TNF-α during the pregnancy period and reviewed the medical records to extract clinical details. The exposed cohort (n = 113, 51.6%) constituted pregnancies exposed to anti-TNF-α during the third trimester, and the unexposed cohort (n = 106, 48.4%) constituted pregnancies with no anti-TNF-α during the third trimester. The association between anti-TNF-α therapy in the third trimester and adverse birth outcomes was studied (1) in those women who had clinical disease activity during pregnancy and (2) in women who had no clinical disease activity during pregnancy. RESULTS In women with disease activity, treated with anti-TNF-α during the third trimester, we found an adjusted odds ratio of 2.23 (95% confidence interval [CI], 0.80-6.20) for preterm birth and 1.16 (95% CI, 0.26-5.23) for LBW. Among women without disease activity, treated with anti-TNF-α therapy during the third trimester, we found an adjusted odds ratio of 3.36 (95% CI, 0.31-36.46) for preterm birth and 0.86 (95% CI, 0.05-14.95) for LBW. CONCLUSIONS For anti-TNF-α therapy in the third trimester, we found no statistically significant increased risk of either LBW or preterm birth.
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Wei SC, Chang TA, Chao TH, Chen JS, Chou JW, Chou YH, Chuang CH, Hsu WH, Huang TY, Hsu TC, Lin CC, Lin HH, Lin JK, Lin WC, Ni YH, Shieh MJ, Shih IL, Shun CT, Tsang YM, Wang CY, Wang HY, Weng MT, Wu DC, Wu WC, Yen HH, Wong JM. Management of Crohn's disease in Taiwan: consensus guideline of the Taiwan Society of Inflammatory Bowel Disease. Intest Res 2017; 15:285-310. [PMID: 28670226 PMCID: PMC5478754 DOI: 10.5217/ir.2017.15.3.285] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Revised: 05/02/2017] [Accepted: 05/02/2017] [Indexed: 12/12/2022] Open
Abstract
Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.
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Affiliation(s)
- Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ting-An Chang
- Department of Pathology, Taipei City Hospital Renai Branch, Taipei, Taiwan
| | - Te-Hsin Chao
- Division of Colorectal Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jinn-Shiun Chen
- Division of Colorectal Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Jen-Wei Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Yenn-Hwei Chou
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Chiao-Hsiung Chuang
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University College of Medicine, Tainan, Taiwan
| | - Wen-Hung Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Municipal Hsiaokang Hospital, Kaohsiung, Taiwan
| | - Tien-Yu Huang
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tzu-Chi Hsu
- Division of Colon and Rectal Surgery, Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan
| | - Chun-Chi Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hung-Hsin Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Surgery, National Yang-Ming University, Taipei, Taiwan
| | - Jen-Kou Lin
- Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Wei-Chen Lin
- Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Jium Shieh
- Department of Oncology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - I-Lun Shih
- Department of Medical Imaging, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Chia-Tung Shun
- Department of Pathology and Forensic Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yuk-Ming Tsang
- Division of Medical Imaging, Department of Radiology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.,MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.,MacKay Medical College, New Taipei City, Taiwan
| | - Meng-Tzu Weng
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Wen-Chieh Wu
- Division of Gastroenterology, Department of Medicine, Taipei City Hospital Renai Branch, Taipei, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Jau-Min Wong
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
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Kammerlander H, Nielsen J, Kjeldsen J, Knudsen T, Friedman S, Nørgård B. The Effect of Disease Activity on Birth Outcomes in a Nationwide Cohort of Women with Moderate to Severe Inflammatory Bowel Disease. Inflamm Bowel Dis 2017; 23:1011-1018. [PMID: 28346274 DOI: 10.1097/mib.0000000000001102] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Active inflammatory bowel disease (IBD) during conception and pregnancy may increase the risk of adverse birth outcomes. Former studies have examined heterogeneous groups of women with varying degrees of IBD severity. We aimed to examine the effect of active IBD on birth outcomes in a more homogeneous group of women with a moderate to severe disease course. Since in Denmark, moderate to severe IBD is an indication for use of anti-tumor necrosis factor-α therapy, we examined all women who used anti-tumor necrosis factor therapy during pregnancy. METHODS We identified a nationwide cohort of 219 singleton pregnancies in women treated with anti-tumor necrosis factor-α therapy during pregnancy (2005-2014). Pregnancies with clinical disease activity (65.8%) constituted the exposed cohort and pregnancies without disease activity constituted the unexposed (34.2%). Disease activity scores were supported by levels of fecal calprotectin. Outcomes included low birth weight, preterm birth, and congenital anomalies. RESULTS In women with IBD, disease activity was associated with adjusted odds ratio of low birth weight and preterm birth; 2.05 (95% confidence interval, 0.37-11.35) and 2.64 (95% confidence interval, 0.85-8.17), respectively. In those with clinical moderate to severe disease activity, the odds ratio for preterm birth was 3.60 (95% confidence interval, 1.14-11.36). In women with ulcerative colitis and disease activity, 19.5% had a child with low birth weight and 29.3% gave birth preterm. CONCLUSION In women with moderate to severe IBD, 66% experienced disease activity during pregnancy. In those with the highest degree of disease activity, the risk of preterm birth was increased 3 to 4 folds. The proportion of adverse birth outcomes was high, particularly among women with ulcerative colitis and disease activity.
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Affiliation(s)
- Heidi Kammerlander
- *Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark; †Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark; ‡Department of Medical Gastroenterology, Hospital of Southwest Jutland, Esbjerg, Denmark; and §Crohn's and Colitis Center, Brigham and Women's Hospital, Boston, Massachusetts and Harvard Medical School, Boston, Massachusetts
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Biancone L, Annese V, Ardizzone S, Armuzzi A, Calabrese E, Caprioli F, Castiglione F, Comberlato M, Cottone M, Danese S, Daperno M, D'Incà R, Frieri G, Fries W, Gionchetti P, Kohn A, Latella G, Milla M, Orlando A, Papi C, Petruzziello C, Riegler G, Rizzello F, Saibeni S, Scribano ML, Vecchi M, Vernia P, Meucci G. Safety of treatments for inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD). Dig Liver Dis 2017; 49:338-358. [PMID: 28161290 DOI: 10.1016/j.dld.2017.01.141] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Revised: 12/19/2016] [Accepted: 01/07/2017] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.
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Affiliation(s)
- Livia Biancone
- Gastroenterology Unit, University of Rome "Tor Vergata", Department of Systems Medicine, Rome, Italy.
| | - Vito Annese
- AOU Careggi, Gastroenterology, Florence, Italy
| | - Sandro Ardizzone
- Gastrointestinal Unit, ASST Fatebenefratelli Sacco - University of Milan, Milan, Italy
| | - Alessandro Armuzzi
- IBD Unit, Presidio Columbus, Fondazione Policlinico Gemelli Universita' Cattolica, Rome, Italy
| | - Emma Calabrese
- Gastroenterology Unit, University of Rome "Tor Vergata", Department of Systems Medicine, Rome, Italy
| | - Flavio Caprioli
- Department of Pathophysiology and Transplantation, University of Milan and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda,Ospedale Policlinico di Milano, Milan, Italy
| | | | - Michele Comberlato
- Department of Gastroenterology and Digestive Endoscopy, Central Hospital, Bolzano, Italy
| | - Mario Cottone
- Division of Internal Medicine 2, IBD Unit, Hospital "Riuniti Villa Sofia-Cervello", Palermo, Italy
| | - Silvio Danese
- Humanitas Research Hospital and Humanitas University, Rozzano (Milan), Italy
| | - Marco Daperno
- Hospital "Ordine Mauriziano di Torino", Turin, Italy
| | - Renata D'Incà
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Italy
| | - Giuseppe Frieri
- University of L'Aquila, Gastroenterology Unit, L'Aquila, Italy
| | - Walter Fries
- Department of Clinical and Experimental Medicine, Clinical Unit for Chroric Bowel Disorders, University of Messina, Messina, Italy
| | - Paolo Gionchetti
- IBD Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Anna Kohn
- San Camillo-Forlanini Hospital, IBD Unit, Rome, Italy
| | | | | | - Ambrogio Orlando
- Division of Internal Medicine 2, IBD Unit, Hospital "Riuniti Villa Sofia-Cervello", Palermo, Italy
| | - Claudio Papi
- IBD Unit, San Filippo Neri Hospital, Rome, Italy
| | - Carmelina Petruzziello
- Gastroenterology Unit, University of Rome "Tor Vergata", Department of Systems Medicine, Rome, Italy
| | - Gabriele Riegler
- U.O. of Gastroenterology C.S. - University della Campania "Luigi Vanvitelli", Naples, Italy
| | - Fernando Rizzello
- IBD Unit, Department of Medical and Surgical Sciences, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Simone Saibeni
- Gastroenterology Unit, Rho Hospital, ASST Rhodense, Rho, Italy
| | | | - Maurizio Vecchi
- Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato and University of Milan, San Donato Milanese, Milan, Italy
| | - Piero Vernia
- Gastroenterology Unit, Sapienza, University of Rome, Rome, Italy
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Mahadevan U, Vermeire S, Lasch K, Abhyankar B, Bhayat F, Blake A, Dubinsky M. Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease. Aliment Pharmacol Ther 2017; 45:941-950. [PMID: 28169436 DOI: 10.1111/apt.13960] [Citation(s) in RCA: 84] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Revised: 10/18/2016] [Accepted: 01/08/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND Vedolizumab is a gut-selective immunoglobulin G1 monoclonal antibody to α4 β7 integrin for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Prospective clinical studies of vedolizumab in pregnancy have not been conducted; therefore, existing safety data of vedolizumab in pregnancy were examined. AIM To assess pregnancy outcomes in females and partners of males who received vedolizumab. METHODS All pregnancy data collected during the clinical programme (from 14 May 2007 to 27 June 2013) and in the post-marketing setting (to 19 November 2015) were analysed. RESULTS Across six studies, there were 27 pregnancies in female participants and 19 pregnancies in partners of male participants. Among 24 vedolizumab-treated females (23 with CD/UC, one healthy volunteer), there were 11 live births, five elective terminations, four spontaneous abortions and four undocumented outcomes. A congenital corpus callosum agenesis anomaly was reported in one live birth from a healthy volunteer with extensive obstetric history exposed to single-dose vedolizumab 79 days before estimated conception. Of 19 pregnancies in partners of male participants, there were 11 live births, two spontaneous abortions, three elective terminations and three undocumented outcomes. Post-marketing reports recorded 81 pregnancies, resulting in four live births, 11 spontaneous abortions and 66 pregnancies that were on-going or reported undocumented outcomes. CONCLUSIONS Initial analysis, limited by sample size and follow-up, identified no new safety concerns for pregnancy outcomes in females directly or indirectly exposed to vedolizumab. However, vedolizumab should be used during pregnancy only if the benefits to the mother outweigh the risks to the mother/unborn child.
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Affiliation(s)
- U Mahadevan
- Center for Colitis and Crohn's Disease, University of California San Francisco, San Francisco, CA, USA
| | - S Vermeire
- University Hospital Gasthuisberg, Leuven, Belgium
| | - K Lasch
- Takeda Pharmaceuticals USA, Inc., Deerfield, IL, USA
| | - B Abhyankar
- Takeda Development Centre Europe Ltd, London, UK
| | - F Bhayat
- Takeda Development Centre Europe Ltd, London, UK
| | - A Blake
- Takeda Development Centre Europe Ltd, London, UK
| | - M Dubinsky
- Department of Pediatrics, Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Hoxha A, Calligaro A, Di Poi E, Peccatori S, Favaro M, Del Ross T, Ramonda R, Grava C, Raffeiner B, Ravagni P, De Vita S, Ruffatti A. Pregnancy and foetal outcomes following anti-tumor necrosis factor alpha therapy: A prospective multicentre study. Joint Bone Spine 2017; 84:169-173. [DOI: 10.1016/j.jbspin.2016.03.014] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2015] [Accepted: 03/24/2016] [Indexed: 02/07/2023]
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