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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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Bokemeyer B, Ghiani M, Fuchs A, Deiters B, Hardtstock F, Brandes A, Knop J, Orzechowski HD, Wilke T. Indicators of active disease and steroid dependency in patients with inflammatory bowel diseases not treated with biologics in a German real-world-setting. Int J Colorectal Dis 2020; 35:1587-1598. [PMID: 32424526 PMCID: PMC7340655 DOI: 10.1007/s00384-020-03588-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/04/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND AIMS While a minority of inflammatory bowel disease (IBD) patients receives biologics in Germany, little is known about therapeutic needs of patients receiving non-biologic therapies. This study aimed to identify indicators of active disease/steroid dependency in patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) treated with conventional therapies and to describe health care resource use (HCRU)/cost. METHODS CD/UC patients treated with immunosuppressants (IS) and/or systemic or locally acting oral corticosteroids (CS) were identified in German claims data (2013-2017) and followed for 12 months post-therapy start. Indicators of active disease/steroid dependency during follow-up period were (i) ≥ 2 prescriptions of CS (sensitivity ≥ 4) or (ii) ≥ 1 IBD-related surgery or (iii) > 7 days IBD-related hospitalization(s). RESULTS Of 9871 included IBD patients (5170 CD, 4701 UC), 25.7%/19.9% (CD/UC) received ≥ 2 prescriptions of CS (sensitivity, 17.4%/15.7%) (i), 3.2% experienced IBD-related surgeries (ii), and 2.5% > 7 days of hospitalizations (iii). Altogether, 44.4% had indicators of active disease/steroid dependency (sensitivity, 23.9%). Among patients with active disease/steroid dependency, 78.0% received CS monotherapy at baseline. Of these, 89.6% received a CS monotherapy in the follow-up period, too. Proportionally, fewer patients with CS monotherapy (57.4%) than IS therapy (91.0%) visited a specialist. HCRU/cost per patient year was significantly higher in patients with than without active disease/steroid dependency. CONCLUSIONS A substantial percentage of biologic-naïve IBD patients suffers from active disease/steroid dependency. The majority receives a monotherapy with systemic CS. Referral to gastroenterologists for treatment optimization is recommended, also because active disease/steroid dependency is associated with increased HCRU/cost.
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Affiliation(s)
- B. Bokemeyer
- Gastroenterology Practice Minden, Minden, Germany
| | | | | | | | | | - A. Brandes
- Takeda Pharma Vertrieb GmbH & Co. KG, Berlin, Germany
| | - J. Knop
- Takeda Pharma Vertrieb GmbH & Co. KG, Berlin, Germany
| | | | - T. Wilke
- Ingress-Health HWM GmbH, Alter Holzhafen 19, 23966 Wismar, Germany
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Cooley LF, Wren J, Keeter MK, Lam I, Bennett N, Brannigan RE. Anti-TNF agents and potential effects on male fertility: are men being counseled? BMC Urol 2020; 20:111. [PMID: 32718310 PMCID: PMC7385975 DOI: 10.1186/s12894-020-00658-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2019] [Accepted: 06/22/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Adult men with autoimmune conditions are commonly prescribed anti-tumor necrosis factor (anti-TNF) agents; however, there is a paucity of quality evidence as to their effect on male fertility (e.g. semen parameters and sperm quality). Our objective was to determine if men with autoimmune conditions are being counseled regarding the unknown reproductive effects of anti-TNF agents prior to initiation of therapy. METHODS A retrospective analysis of 1010 male patients age 18-45 who were prescribed an anti-TNF agent were assessed for (1) receipt of counseling regarding potential reproductive effects; (2) screening for anatomic or laboratory abnormalities associated with infertility; (3) election for sperm cryopreservation. RESULTS Only 10.3% of men received counseling, and this was not associated with age (p = 0.77). Those who received counseling were significantly more likely to have a genitourinary exam performed, be assessed for presence of a varicocele, be asked about or endorse low libido or erectile dysfunction, have a testosterone, LH, FSH, or prolactin level checked, and have a semen analysis performed (all, p < 0.0001). Rates of sperm cryopreservation were low, but statistically higher in men who received counseling (5.77% (+) counseling, 1.10% (-) counseling) (p = 0.002). CONCLUSIONS The limited current literature lacks a consensus regarding the short- and long-term male reproductive effects of anti-TNF therapy. Despite this lack of clarity, rates of pre-initiation counseling were low. Rates of sperm cryopreservation, while improved in the counseled group remained low, suggesting prescribing physicians may be unaware of this option for patients.
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Affiliation(s)
- Lauren Folgosa Cooley
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - James Wren
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - Mary Kate Keeter
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - Isaac Lam
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - Nelson Bennett
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA
| | - Robert E Brannigan
- Department of Urology, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St. Arkes 23-015, Chicago, IL, 60611, USA.
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Meyer A, Rudant J, Drouin J, Coste J, Carbonnel F, Weill A. The effectiveness and safety of infliximab compared with biosimilar CT-P13, in 3112 patients with ulcerative colitis. Aliment Pharmacol Ther 2019; 50:269-277. [PMID: 31115919 PMCID: PMC6767082 DOI: 10.1111/apt.15323] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 03/20/2019] [Accepted: 05/06/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND CT-P13, a biosimilar of the reference product infliximab, has been approved for the treatment of ulcerative colitis on the basis of the results of trials conducted in patients with spondyloarthritis and rheumatoid arthritis. AIM To compare the effectiveness and safety of CT-P13 and the reference product in infliximab-naive patients with ulcerative colitis METHODS: A comparative real-life equivalence cohort study was conducted using the French nationwide health administrative database. Infliximab-naive patients with ulcerative colitis over 15 years of age who started infliximab with no other indications for infliximab were included. The primary outcome was a composite endpoint (death, ulcerative colitis-related surgery, all-cause hospitalisation and reimbursement for other biologics). Equivalence was defined as a 95% CI of the hazard ratio (HR) of CT-P13 vs the reference product, in a multivariable marginal Cox model situated within prespecified margins of (0.80-1.25). RESULTS A total of 3112 patients were included between 1 January 2015 and 30 June 2017: 1434 received the reference product, 1678 received CT-P13. Overall, 710 patients in the reference product group and 743 patients in the CT-P13 group met the composite endpoint. In multivariable analysis of the primary outcome, CT-P13 was equivalent to the reference product (HR 1.04; 95% CI: 0.94-1.15). The number of serious infections was lower in the CT-P13 group (HR 0.65; 95% CI: 0.48-0.88). There was no difference in the incidence of solid or haematologic malignancy (HR 0.81; 95% CI: 0.41-1.60). CONCLUSIONS The effectiveness of CT-P13 is equivalent and the risk of serious infections could be lower than that of the reference product for infliximab-naive patients with ulcerative colitis.
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Affiliation(s)
- Antoine Meyer
- Caisse Nationale de l’Assurance Maladie (CNAM)ParisFrance,Service de gastroentérologie, BicêtreAssistance Publique-Hôpitaux de ParisLe Kremlin BicêtreFrance,Université Paris SudLe Kremlin BicêtreFrance
| | - Jérémie Rudant
- Caisse Nationale de l’Assurance Maladie (CNAM)ParisFrance
| | - Jérôme Drouin
- Caisse Nationale de l’Assurance Maladie (CNAM)ParisFrance
| | - Joël Coste
- Biostatistique et EpidémiologieHôtel-Dieu, Assistance Publique-Hôpitaux de ParisParisFrance
| | - Franck Carbonnel
- Service de gastroentérologie, BicêtreAssistance Publique-Hôpitaux de ParisLe Kremlin BicêtreFrance,Université Paris SudLe Kremlin BicêtreFrance
| | - Alain Weill
- Caisse Nationale de l’Assurance Maladie (CNAM)ParisFrance
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Swann R, Boal A, Squires SI, Lamb C, Clark LL, Lamont S, Naismith G. Optimising IBD patient selection for de-escalation of anti-TNF therapy to immunomodulator maintenance. Frontline Gastroenterol 2019; 11:16-21. [PMID: 31885835 PMCID: PMC6914296 DOI: 10.1136/flgastro-2018-101135] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2018] [Revised: 04/08/2019] [Accepted: 04/08/2019] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE Inflammatory bowel disease (IBD) is increasingly managed with the use of biologic therapies. National guidelines (National Institute for Health and Care Excellence (NICE)) suggest considering cessation after 1 year of therapy but lack detailed criteria for this. We aimed to describe clinical outcomes from the introduction of a biologic review panel (BRP) to implement modified criteria for cessation of antitumour necrosis factor (anti-TNF) therapy and step down to single-agent immunomodulator. DESIGN Retrospective review of patient outcomes following BRP implementation. PATIENTS All patients on biologic therapy discussed in the BRP within a 5-year period. SETTING Single IBD network covering three hospital sites. INTERVENTIONS Modified criteria for biologic cessation were based on published evidence; they excluded individuals with no suitable maintenance immunomodulator, previous surgery or evidence of active disease, additional indications for anti-TNF therapy and previous relapse on biologic cessation. All patients with IBD on a biologic were discussed at the BRP. MAIN OUTCOME MEASURES Relapse following IBD cessation and relative cost of BRP. RESULTS 136 patients with IBD were reviewed, with 45 patients meeting the NICE guideline criteria for cessation. The BRP and modified criteria affected decision to withdraw therapy in 38% of these. Therapy was withdrawn in 27 patients, with a 20% 24-month relapse rate. Younger age at cessation was significantly associated with relapse (p=0.01). CONCLUSION The BRP approach has proved a safe and effective means of decision making in stopping biologic therapy. Future work to inform exclusion criteria is required.
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Affiliation(s)
- Rachael Swann
- Department of Gastroenterology, Royal Alexandra Hospital, NHS Greater Glasgow and Clyde Division, Glasgow, UK
| | - Alan Boal
- Department of Gastroenterology, Royal Alexandra Hospital, NHS Greater Glasgow and Clyde Division, Glasgow, UK
| | - Seth Ian Squires
- Department of Gastroenterology, Royal Alexandra Hospital, NHS Greater Glasgow and Clyde Division, Glasgow, UK
| | - Carly Lamb
- Department of Gastroenterology, Royal Alexandra Hospital, NHS Greater Glasgow and Clyde Division, Glasgow, UK
| | - Laura Louise Clark
- Department of Gastroenterology, Royal Alexandra Hospital, NHS Greater Glasgow and Clyde Division, Glasgow, UK
| | - Selina Lamont
- Department of Gastroenterology, Royal Alexandra Hospital, NHS Greater Glasgow and Clyde Division, Glasgow, UK
| | - Graham Naismith
- Department of Gastroenterology, Royal Alexandra Hospital, NHS Greater Glasgow and Clyde Division, Glasgow, UK
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Olivera P, Danese S, Jay N, Natoli G, Peyrin-Biroulet L. Big data in IBD: a look into the future. Nat Rev Gastroenterol Hepatol 2019; 16:312-321. [PMID: 30659247 DOI: 10.1038/s41575-019-0102-5] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Big data methodologies, made possible with the increasing generation and availability of digital data and enhanced analytical capabilities, have produced new insights to improve outcomes in many disciplines. Application of big data in the health-care sector is in its early stages, although the potential for leveraging underutilized data to gain a better understanding of disease and improve quality of care is enormous. Owing to the intrinsic characteristics of inflammatory bowel disease (IBD) and the management dilemmas that it imposes, the implementation of big data research strategies not only can complement current research efforts but also could represent the only way to disentangle the complexity of the disease. In this Review, we explore important potential applications of big data in IBD research, including predictive models of disease course and response to therapy, characterization of disease heterogeneity, drug safety and development, precision medicine and cost-effectiveness of care. We also discuss the strengths and limitations of potential data sources that big data analytics could draw from in the field of IBD, including electronic health records, clinical trial data, e-health applications and genomic, transcriptomic, proteomic, metabolomic and microbiomic data.
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Affiliation(s)
- Pablo Olivera
- Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy.,Humanitas Clinical Research Hospital, Rozzano, Milan, Italy
| | - Nicolas Jay
- Orpailleur and Department of Medical Information, LORIA and Nancy University Hospital, Vandoeuvre-lès-Nancy, Nancy, France
| | | | - Laurent Peyrin-Biroulet
- INSERM U954 and Department of Hepatogastroenterology, Nancy University Hospital, Université de Lorraine, Vandoeuvre-lès-Nancy, Nancy, France.
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Meyer A, Rudant J, Drouin J, Weill A, Carbonnel F, Coste J. Effectiveness and Safety of Reference Infliximab and Biosimilar in Crohn Disease: A French Equivalence Study. Ann Intern Med 2019; 170:99-107. [PMID: 30534946 DOI: 10.7326/m18-1512] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND CT-P13 is a biosimilar of the reference product (RP) infliximab, with demonstrated efficacy and safety for some inflammatory arthritides. It was approved for the treatment of Crohn disease (CD) on that basis, without specific studies examining its effects in CD. OBJECTIVE To compare the effectiveness and safety of CT-P13 and RP in infliximab-naive patients with CD. DESIGN Comparative equivalence cohort study. SETTING Système National des Données de Santé (SNDS), a French nationwide health administrative database (1 March 2015 to 30 June 2017). PATIENTS 5050 infliximab-naive patients with CD who were older than 15 years, had started treatment with RP (n = 2551) or CT-P13 (n = 2499), and had no other indications for infliximab. MEASUREMENTS The primary outcome was a composite end point of death, CD-related surgery, all-cause hospitalization, and reimbursement of another biologic therapy. Equivalence was defined as a 95% CI of the hazard ratio (HR) of CT-P13 versus RP in a multivariable marginal Cox model situated within prespecified margins (0.80 to 1.25). RESULTS Overall, 1147 patients in the RP group and 952 patients in the CT-P13 group met the composite end point (including 838 and 719 hospitalizations, respectively). In multivariable analysis of the primary outcome, CT-P13 was equivalent to RP (HR, 0.92 [95% CI, 0.85 to 0.99]). No differences in safety outcomes were observed between the 2 groups: serious infections (HR, 0.82 [CI, 0.61 to 1.11]), tuberculosis (HR, 1.10 [CI, 0.36 to 3.34]), and solid or hematologic cancer (HR, 0.66 [CI, 0.33 to 1.32]). LIMITATION The SNDS does not contain all relevant clinical data (for example, disease activity). CONCLUSION This analysis of real-world data indicates that the effectiveness of CT-P13 is equivalent to that of RP for infliximab-naive patients with CD. No difference was observed for safety outcomes. PRIMARY FUNDING SOURCE Caisse Nationale de l'Assurance Maladie.
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Affiliation(s)
- Antoine Meyer
- Caisse Nationale de l'Assurance Maladie, Paris, and Hôpital Bicêtre, Le Kremlin-Bicêtre, France. (A.M.)
| | - Jérémie Rudant
- Caisse Nationale de l'Assurance Maladie, Paris, France (J.R., J.D., A.W.)
| | - Jérôme Drouin
- Caisse Nationale de l'Assurance Maladie, Paris, France (J.R., J.D., A.W.)
| | - Alain Weill
- Caisse Nationale de l'Assurance Maladie, Paris, France (J.R., J.D., A.W.)
| | | | - Joël Coste
- Caisse Nationale de l'Assurance Maladie, Paris, and Hôpital Bicêtre, Le Kremlin-Bicêtre, France (J.C.)
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Delday M, Mulder I, Logan ET, Grant G. Bacteroides thetaiotaomicron Ameliorates Colon Inflammation in Preclinical Models of Crohn's Disease. Inflamm Bowel Dis 2019; 25:85-96. [PMID: 30215718 PMCID: PMC6290787 DOI: 10.1093/ibd/izy281] [Citation(s) in RCA: 140] [Impact Index Per Article: 23.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Indexed: 12/12/2022]
Abstract
Background Alterations in the gut microbiota are strongly associated with the development of inflammatory bowel disease (IBD), particularly with Crohn's disease, which is characterized by reduced abundance of commensal anaerobic bacteria including members of the Bacteroides genus. Our aim was to investigate the protective effects of Bacteroides thetaiotaomicron, an abundant member of this genus, in different rodent models of IBD. Methods We assessed the effect of B. thetaiotaomicron administration on primary readouts of colitis (weight loss, histopathology, and immune parameters) in dextran sodium sulphate (DSS) and interleukin-10 knockout (IL10KO) models of IBD. Efficacy of a freeze-dried bacterial formulation and a purified recombinant protein of B. thetaiotaomicron was also investigated. Results B. thetaiotaomicron showed protective effects in both DSS and IL10KO rodent models, as demonstrated by significant amelioration of weight loss, colon shortening, histopathological damage and immune activation. This efficacy was not exclusive to actively growing bacterial preparations but was retained by freeze-dried cells of B. thetaiotaomicron. A pirin-like protein (PLP) of B. thetaiotaomicron, identified by microarray analysis during coculture of the bacterial strain with Caco-2 cells, reduced pro-inflammatory NF-κB signalling in these intestinal epithelial cells. Recombinant PLP partially recapitulated the effect of the whole strain in a rat DSS model. Conclusions B. thetaiotaomicron displays strong efficacy in preclinical models of IBD and protects against weight loss, histopathological changes in the colon and inflammatory markers. These data indicate that the live strain or its products may be a novel alternative to current treatment options for Crohn's disease.
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Affiliation(s)
- Margaret Delday
- 4D Pharma Research Ltd, Life Science Innovation Building, Aberdeen, UK
- Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen UK
| | - Imke Mulder
- 4D Pharma Research Ltd, Life Science Innovation Building, Aberdeen, UK
| | - Elizabeth T Logan
- 4D Pharma Research Ltd, Life Science Innovation Building, Aberdeen, UK
- Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen UK
| | - George Grant
- 4D Pharma Research Ltd, Life Science Innovation Building, Aberdeen, UK
- Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen UK
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Value of a national administrative database to guide public decisions: From the système national d’information interrégimes de l’Assurance Maladie (SNIIRAM) to the système national des données de santé (SNDS) in France. Rev Epidemiol Sante Publique 2017; 65 Suppl 4:S149-S167. [DOI: 10.1016/j.respe.2017.05.004] [Citation(s) in RCA: 337] [Impact Index Per Article: 42.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Revised: 05/18/2017] [Accepted: 05/18/2017] [Indexed: 12/11/2022] Open
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Safety Considerations with the Use of Corticosteroids and Biologic Therapies in Mild-to-Moderate Ulcerative Colitis. Inflamm Bowel Dis 2017; 23:1689-1701. [PMID: 28906290 DOI: 10.1097/mib.0000000000001261] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND The risk of corticosteroid-associated adverse events can limit the use of systemic corticosteroids. Oral, topically acting, second-generation corticosteroids that deliver drug to the site of inflammation, and biologic therapies, are effective treatment alternatives. The aim of this review was to evaluate the safety and tolerability of topically acting corticosteroids and biologic therapies versus oral systemic corticosteroids for ulcerative colitis (UC). METHODS The PubMed database was searched for clinical and observational trials, systematic reviews, and case reports/series published between January 1950 and September 30, 2016. Search terms used included "corticosteroids," "beclomethasone dipropionate," "budesonide," "infliximab," "adalimumab," "golimumab," and "vedolizumab" in combination with "ulcerative colitis" or "inflammatory bowel disease." RESULTS A total of 582 studies were identified from PubMed searches. Only 1 direct comparative trial for oral topically acting corticosteroids and systemic corticosteroids was available, and no comparative trials versus biologic therapies were identified. In patients with mild-to-moderate UC, short-term (4-8 wk) oral beclomethasone dipropionate or oral budesonide multimatrix system demonstrated safety profiles comparable with placebo with few corticosteroid-related adverse events reported. Based on long-term data in patients with moderate-to-severe UC, biologics have a generally tolerable adverse event profile, although infections, infusion reactions, and autoimmune disorders were frequently reported. CONCLUSIONS Second-generation corticosteroids, beclomethasone dipropionate and budesonide multimatrix system, exhibited a favorable safety profile in patients with mild-to-moderate UC. For biologics, which are only indicated in moderate-to-severe UC, additional studies are needed to further ascertain the benefit to risk profile of these agents in patients with mild-to-moderate disease (see Video Abstract, Supplemental Digital Content, http://links.lww.com/IBD/B653).
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Gouverneur A, Dolatkhani D, Rouyer M, Grelaud A, Francis F, Gilleron V, Fourrier-Réglat A, Noize P. Agreement between hospital discharge diagnosis codes and medical records to identify metastatic colorectal cancer and associated comorbidities in elderly patients. Rev Epidemiol Sante Publique 2017; 65:321-325. [PMID: 28576381 DOI: 10.1016/j.respe.2017.03.132] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 02/01/2017] [Accepted: 03/15/2017] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Quality of coding to identify cancers and comorbidities through the French hospital diagnosis database (Programme de médicalisation des systèmes d'information, PMSI) has been little investigated. Agreement between medical records and PMSI database was evaluated regarding metastatic colorectal cancer (mCRC) and comorbidities. METHODS From 01/01/2013 to 06/30/2014, 74 patients aged≥65years at mCRC diagnosis were identified in Bordeaux teaching hospital. Data on mCRC and comorbidities were collected from medical records. All diagnosis codes (main, related and associated) registered into the PMSI were extracted. Agreement between sources was evaluated using the percent agreement for mCRC and the kappa (κ) statistic for comorbidities. RESULTS Agreement for primary CRC and mCRC was higher using all types of diagnosis codes instead of the main one exclusively (respectively 95% vs. 53% for primary CRC and 91% vs. 24% for mCRC). Agreement was substantial (κ 0.65) for cardiovascular diseases, notably atrial fibrillation (κ 0.77) and hypertension (κ 0.68). It was moderate for psychiatric disorders (κ 0.49) and respiratory diseases (κ 0.48), although chronic obstructive pulmonary disease had a good agreement (κ 0.75). Within the class of endocrine, nutritional and metabolic diseases (κ 0.55), agreement was substantial for diabetes (κ 0.91), obesity (κ 0.82) and hypothyroidism (κ 0.72) and moderate for hypercholesterolemia (κ 0.51) and malnutrition (κ 0.42). CONCLUSION These results are reassuring with regard to detection through PMSI of mCRC if all types of diagnosis codes are considered and useful to better choose comorbidities in elderly mCRC patients that could be well identified through hospital diagnosis codes.
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Affiliation(s)
- A Gouverneur
- CHU de Bordeaux, 33000 Bordeaux, France; University de Bordeaux, 33076 Bordeaux cedex, France; Inserm U1219, 33076 Bordeaux cedex, France; Inserm CIC1401, 33076 Bordeaux cedex, France.
| | - D Dolatkhani
- CHU de Bordeaux, 33000 Bordeaux, France; University de Bordeaux, 33076 Bordeaux cedex, France
| | - M Rouyer
- Inserm CIC1401, 33076 Bordeaux cedex, France; ADERA, 33608 Pessac, France
| | - A Grelaud
- Inserm CIC1401, 33076 Bordeaux cedex, France; ADERA, 33608 Pessac, France
| | - F Francis
- CHU de Bordeaux, 33000 Bordeaux, France; University de Bordeaux, 33076 Bordeaux cedex, France
| | | | - A Fourrier-Réglat
- CHU de Bordeaux, 33000 Bordeaux, France; University de Bordeaux, 33076 Bordeaux cedex, France; Inserm U1219, 33076 Bordeaux cedex, France; Inserm CIC1401, 33076 Bordeaux cedex, France
| | - P Noize
- CHU de Bordeaux, 33000 Bordeaux, France; Inserm U1219, 33076 Bordeaux cedex, France; Inserm CIC1401, 33076 Bordeaux cedex, France
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Trends in Narcotic and Corticosteroid Prescriptions in Patients with Inflammatory Bowel Disease in the United States Ambulatory Care Setting from 2003 to 2011. Inflamm Bowel Dis 2017; 23:868-874. [PMID: 28368911 DOI: 10.1097/mib.0000000000001084] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND/HYPOTHESIS Before the availability of biological therapies, corticosteroids and narcotics were frequently used in patients with inflammatory bowel disease (IBD) because of a paucity of disease-modifying therapies. The increased accessibility to effective biologicals for IBD over the last decade should be leading to less use of corticosteroids and narcotic medications. This study aims to examine trends in prescriptions of corticosteroids and narcotics to patients with IBD in the United States during the period 2003 to 2011. METHODS Data from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey were used to examine visits of patients with IBD. Trends in corticosteroid and narcotic prescriptions were explored, and predictors of use were assessed using survey-weighted chi-square tests. RESULTS From 2003 to 2011, a total of 1119 patients with IBD had visits recorded in the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey databases. Although biological prescriptions significantly increased from 3.3% in 2003 to 2005 to 15.9% in 2009 to 2011 (P = 0.004), there was no significant decrease in corticosteroid or narcotic prescriptions during this same time frame. Patients with IBD were less likely to receive narcotics (odds ratio = 0.38) when seeing a medical specialist compared with primary care physicians or surgeons. CONCLUSIONS Despite the availability of more effective biological therapies, prescriptions for corticosteroids and narcotics did not decline in patients with IBD visiting U.S. ambulatory clinics and emergency departments from 2003 to 2011.
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Bezin J, Duong M, Lassalle R, Droz C, Pariente A, Blin P, Moore N. The national healthcare system claims databases in France, SNIIRAM and EGB: Powerful tools for pharmacoepidemiology. Pharmacoepidemiol Drug Saf 2017; 26:954-962. [PMID: 28544284 DOI: 10.1002/pds.4233] [Citation(s) in RCA: 411] [Impact Index Per Article: 51.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 03/30/2017] [Accepted: 04/23/2017] [Indexed: 12/11/2022]
Affiliation(s)
- Julien Bezin
- Department of Medical Pharmacology, CHU de Bordeaux; Université de Bordeaux; 33076 Bordeaux France
- INSERM U1219; 33076 Bordeaux France
| | - Mai Duong
- INSERM U1219; 33076 Bordeaux France
- Bordeaux PharmacoEpi; INSERM CIC1401; 33076 Bordeaux France
| | - Régis Lassalle
- Bordeaux PharmacoEpi; INSERM CIC1401; 33076 Bordeaux France
| | - Cécile Droz
- Bordeaux PharmacoEpi; INSERM CIC1401; 33076 Bordeaux France
| | - Antoine Pariente
- Department of Medical Pharmacology, CHU de Bordeaux; Université de Bordeaux; 33076 Bordeaux France
- INSERM U1219; 33076 Bordeaux France
| | - Patrick Blin
- Bordeaux PharmacoEpi; INSERM CIC1401; 33076 Bordeaux France
| | - Nicholas Moore
- Department of Medical Pharmacology, CHU de Bordeaux; Université de Bordeaux; 33076 Bordeaux France
- INSERM U1219; 33076 Bordeaux France
- Bordeaux PharmacoEpi; INSERM CIC1401; 33076 Bordeaux France
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14
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Severs M, Mangen MJJ, van der Valk ME, Fidder HH, Dijkstra G, van der Have M, van Bodegraven AA, de Jong DJ, van der Woude CJ, Romberg-Camps MJL, Clemens CHM, Jansen JM, van de Meeberg PC, Mahmmod N, Ponsioen CY, Vermeijden JR, van der Meulen-de Jong AE, Pierik M, Siersema PD, Oldenburg B. Smoking is Associated with Higher Disease-related Costs and Lower Health-related Quality of Life in Inflammatory Bowel Disease. J Crohns Colitis 2017; 11:342-352. [PMID: 27647859 DOI: 10.1093/ecco-jcc/jjw160] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Accepted: 09/17/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Smoking affects the course of inflammatory bowel disease [IBD]. We aimed to study the impact of smoking on IBD-specific costs and health-related quality-of-life [HrQoL] among adults with Crohn's disease [CD] and ulcerative colitis [UC]. METHODS A large cohort of IBD patients was prospectively followed during 1 year using 3-monthly questionnaires on smoking status, health resources, disease activity and HrQoL. Costs were calculated by multiplying used resources with corresponding unit prices. Healthcare costs, patient costs, productivity losses, disease course items and HrQoL were compared between smokers, never-smokers and ex-smokers, adjusted for potential confounders. RESULTS In total, 3030 patients [1558 CD, 1054 UC, 418 IBD-unknown] were enrolled; 16% smoked at baseline. In CD, disease course was more severe among smokers. Smoking was associated with > 30% higher annual societal costs in IBD (€7,905 [95% confidence interval €6,234 - €9,864] vs €6,017 [€5,186 - €6,946] in never-smokers and €5,710 [€4,687 - €6,878] in ex-smokers, p = 0.06 and p = 0.04, respectively). In CD, smoking patients generated the highest societal costs, primarily driven by the use of anti-tumour necrosis factor compounds. In UC, societal costs of smoking patients were comparable to those of non-smokers. Societal costs of IBD patients who quitted smoking > 5 years before inclusion were lower than in patients who quitted within the past 5 years (€ 5,135 [95% CI €4,122 - €6,303] vs €9,342 [€6,010 - €12,788], p = 0.01). In both CD and UC, smoking was associated with a lower HrQoL. CONCLUSIONS Smoking is associated with higher societal costs and lower HrQoL in IBD patients. Smoking cessation may result in considerably lower societal costs.
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Affiliation(s)
- M Severs
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - M-J J Mangen
- Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - M E van der Valk
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - H H Fidder
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - G Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, The Netherlands
| | - M van der Have
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - A A van Bodegraven
- Department of Gastroenterology and Hepatology, VU University Medical Centre, Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology [Co-MIK], Zuyderland Medical Centre, Heerlen, Sittard, Geleen, The Netherlands
| | - D J de Jong
- Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - C J van der Woude
- Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - M J L Romberg-Camps
- Department of Gastroenterology and Hepatology [Co-MIK], Zuyderland Medical Centre, Heerlen, Sittard, Geleen, The Netherlands
| | - C H M Clemens
- Department of Gastroenterology and Hepatology, Diaconessenhuis, Leiden, The Netherlands
| | - J M Jansen
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - P C van de Meeberg
- Department of Gastroenterology and Hepatology, Slingeland Hospital, Doetinchem, The Netherlands
| | - N Mahmmod
- Department of Gastroenterology and Hepatology, Antonius Hospital, Nieuwegein, The Netherlands
| | - C Y Ponsioen
- Department of Gastroenterology and Hepatology, Academic Medical Centre Amsterdam, Amsterdam, The Netherlands
| | - J R Vermeijden
- Department of Gastroenterology and Hepatology, Meander Medical Centre, Amersfoort, The Netherlands
| | - A E van der Meulen-de Jong
- Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - M Pierik
- Department of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - P D Siersema
- Department of Gastroenterology and Hepatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
| | - B Oldenburg
- Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands
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Shen NY, Bi JB, Zhang JY, Zhang SM, Gu JX, Qu K, Liu C. Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression. World J Gastroenterol 2017; 23:1375-1386. [PMID: 28293084 PMCID: PMC5330822 DOI: 10.3748/wjg.v23.i8.1375] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Revised: 12/20/2016] [Accepted: 01/17/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the therapeutic effect of hydrogen-rich water (HRW) on inflammatory bowel disease (IBD) and to explore the potential mechanisms involved.
METHODS Male mice were randomly divided into the following four groups: control group, in which the mice received equivalent volumes of normal saline (NS) intraperitoneally (ip); dextran sulfate sodium (DSS) group, in which the mice received NS ip (5 mL/kg body weight, twice per day at 8 am and 5 pm) for 7 consecutive days after IBD modeling; DSS + HRW group, in which the mice received HRW (in the same volume as the NS treatment) for 7 consecutive days after IBD modeling; and DSS + HRW + ZnPP group, in which the mice received HRW (in the same volume as the NS treatment) and ZnPP [a heme oxygenase-1 (HO-1) inhibitor, 25 mg/kg] for 7 consecutive days after IBD modeling. IBD was induced by feeding DSS to the mice, and blood and colon tissues were collected on the 7th d after IBD modeling to determine clinical symptoms, colonic inflammation and the potential mechanisms involved.
RESULTS The DSS + HRW group exhibited significantly attenuated weight loss and a lower extent of disease activity index compared with the DSS group on the 7th d (P < 0.05). HRW exerted protective effects against colon shortening and colonic wall thickening in contrast to the DSS group (P < 0.05). The histological study demonstrated milder inflammation in the DSS + HRW group, which was similar to normal inflammatory levels, and the macroscopic and microcosmic damage scores were lower in this group than in the DSS group (P < 0.05). The oxidative stress parameters, including MDA and MPO in the colon, were significantly decreased in the DSS + HRW group compared with the DSS group (P < 0.05). Simultaneously, the protective indicators, superoxide dismutase and glutathione, were markedly increased with the use of HRW. Inflammatory factors were assessed, and the results showed that the DSS + HRW group exhibited significantly reduced levels of TNF-α, IL-6 and IL-1β compared with the DSS group (P < 0.05). In addition, the pivotal proteins involved in endoplasmic reticulum (ER) stress, including p-eIF2α, ATF4, XBP1s and CHOP, were dramatically reduced after HRW treatment in contrast to the control group (P < 0.05). Furthermore, HRW treatment markedly up-regulated HO-1 expression, and the use of ZnPP obviously reversed the protective role of HRW. In the DSS + HRW + ZnPP group, colon shortening and colonic wall thickening were significantly aggravated, and the macroscopic damage scores were similar to those of the DSS + HRW group (P < 0.05). The histological study also showed more serious colonic damage that was similar to the DSS group.
CONCLUSION HRW has a significant therapeutic potential in IBD by inhibiting inflammatory factors, oxidative stress and ER stress and by up-regulating HO-1 expression.
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