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Karp J, Shen H, Goodwin T, Sparrow MP. Anaphylaxis to a Vedolizumab Infusion following Drug Holiday in a Patient with Ulcerative Colitis: A Case Report. Case Rep Gastroenterol 2025; 19:62-66. [PMID: 39981168 PMCID: PMC11820661 DOI: 10.1159/000543387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 12/23/2024] [Indexed: 02/22/2025] Open
Abstract
Introduction Vedolizumab is a commonly prescribed biologic agent due to its safety profile and clinical efficacy. Severe infusion-related reactions are exceedingly rare, with no previously documented cases of anaphylaxis to vedolizumab infusion following a drug holiday. Case Presentation We report the case of a 65-year-old male with ulcerative colitis who had a severe anaphylactic reaction to the first re-induction infusion of vedolizumab following a 30-month drug holiday. No pre-infusion prophylactic medication was administered. Upon commencement of the infusion, the patient developed anaphylactic symptoms including airway compromise that required intensive care unit admission and treatment with an adrenaline infusion. Conclusion Anaphylactic reactions to vedolizumab after a drug holiday can occur. As is done for infliximab, we recommend administration of an antipyretic, antihistamine, and corticosteroid prior to vedolizumab re-induction infusions when it is given after a drug holiday.
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Affiliation(s)
- Jadon Karp
- Department of Gastroenterology, The Alfred Hospital, Melbourne, VIC, Australia
| | - Henry Shen
- Department of Gastroenterology, The Alfred Hospital, Melbourne, VIC, Australia
| | - Thomas Goodwin
- Department of Gastroenterology, The Alfred Hospital, Melbourne, VIC, Australia
| | - Miles P. Sparrow
- Department of Gastroenterology, The Alfred Hospital, Melbourne, VIC, Australia
- School of Translational Medicine, Monash University, Melbourne, VIC, Australia
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Dharmaraj R, Lemon TP, Elmaoued R, Castillo RO, Alkhouri R. Infusion Reactions to Infliximab in Pediatric Patients with Inflammatory Bowel Disease. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1366. [PMID: 39594941 PMCID: PMC11592503 DOI: 10.3390/children11111366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/02/2024] [Accepted: 11/07/2024] [Indexed: 11/28/2024]
Abstract
Infliximab (IFX) is a recombinant DNA-derived chimeric IgG monoclonal antibody protein that inhibits tumor necrosis factor alpha (TNF-α). IFX, like other agents derived from foreign proteins, can cause infusion reactions both during and after the infusion. The incidence of infusion reactions ranges between 0% and 15% in pediatric patients. The potential underlying mechanisms for these reactions may include anaphylaxis and anaphylactoid reactions, cytokine release syndrome, serum sickness-like reactions, and the development of antibodies against IFX. Several precautions can help reduce the risk of a new infusion reaction, such as a gradual increase in the infusion rate, scheduled infusions, and administering premedication or immunomodulators alongside IFX. Acute mild to moderate reactions often resolve spontaneously after a temporary cessation of the infusion or reduction in the infusion rate. Strategies like graded dose challenges and premedication can be utilized to prevent recurrence. In cases of severe reactions, desensitization or switching to an alternative biologic may be considered. This article aims to review the most recent guidelines for managing IFX-related infusion reactions in pediatric patients with inflammatory bowel disease (IBD), relying on the best available evidence.
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Affiliation(s)
- Rajmohan Dharmaraj
- Division of Gastroenterology, Department of Pediatrics, University of New Mexico, Albuquerque, NM 87131, USA; (T.P.L.); (R.E.); (R.O.C.); (R.A.)
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Mori F, Saretta F, Riscassi S, Caimmi S, Bottau P, Liotti L, Franceschini F, Bianchi A, Valluzzi RL, Crisafulli G, Caffarelli C. Risk factors for drug hypersensitivity reactions in children. Ital J Pediatr 2024; 50:127. [PMID: 39010141 PMCID: PMC11247891 DOI: 10.1186/s13052-024-01694-x] [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] [Received: 04/04/2024] [Accepted: 06/25/2024] [Indexed: 07/17/2024] Open
Abstract
Drug hypersensitivity reactions are common in children. Risk factors predisposing to IgE-mediated drug allergies and delayed drug reactions are a matter of debate. Gender, age, previous reactions to the same drug or to another drug, reduced drug metabolism, chronic diseases, polypharmacy, drug doses are linked with the onset of hypersensitivity reactions in some children. Novel advances in genetic polymorphisms can rapidly change the approach to the prevention of reactions since gene testing can be a useful screening test for severe cutaneous adverse reactions. Viral infections may act as cofactors in susceptible individuals. Polypharmacy, high doses, repeated doses and parental route of administration are also risk factors. Clinicians should take into account risk factors to allow the risk-benefit balance to be maintained.
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Affiliation(s)
- Francesca Mori
- Allergy Unit, Meyer Children's Hospital IRCCS, 50139, Florence, Italy
| | - Francesca Saretta
- Dipartimento Materno-Infantile, SC Pediatria, Ospedale Latisana-Palmanova, Azienda Sanitaria Universitaria Friuli Centrale, 33100, Udine, Italy
| | - Sara Riscassi
- UOC Di Pediatria, Ospedale Bolzano, Azienda Sanitaria Dell'Alto Adige, Bolzano, 39100, Italy
| | - Silvia Caimmi
- SC Di Pediatria, Fondazione IRCSS Policlinico San Matteo, 27100, Pavia, Italy
| | - Paolo Bottau
- UOC Di Pediatria E Neonatologia, Ospedale Imola (BO), Imola, 40026, Italy
| | - Lucia Liotti
- UOC Pediatria, Azienda Ospedaliero-Universitaria "Ospedali Riuniti", 60100, Ancona, Italy
| | | | - Annamaria Bianchi
- UOC Pediatria, Azienda Ospedaliera San Camillo Forlanini, 00152, Rome, Italy
| | - Rocco Luigi Valluzzi
- Translational Research in Pediatric Specialties Area, Division of Allergy, Bambino Gesù Children's Hospital, IRCCS, 00165, Rome, Italy
| | - Giuseppe Crisafulli
- Dipartimento Materno-Infantile, UOC Pediatria, University of Messina, Messina, 98122, Italy
| | - Carlo Caffarelli
- Department of Medicine and Surgery, Clinica Pediatrica, Azienda Ospedaliera-Universitaria, University of Parma, 43123, Parma, Italy.
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Wong ECL, Dulai PS, Marshall JK, Jairath V, Reinisch W, Narula N. Delayed Ustekinumab Responders in Ulcerative Colitis Have Greater Inflammatory Burden but Similar Outcomes as Early Responders. Clin Gastroenterol Hepatol 2023; 21:3387-3396.e1. [PMID: 37391059 DOI: 10.1016/j.cgh.2023.06.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 06/02/2023] [Accepted: 06/12/2023] [Indexed: 07/02/2023]
Abstract
BACKGROUND & AIMS Differences in 1-year outcomes among early compared with delayed responders to vedolizumab have been shown in ulcerative colitis. However, it is unclear whether similar differences exist with ustekinumab, and what factors differentiate delayed responders from nonresponders. METHODS This study was a post hoc analysis of patient-level data from the UNIFI clinical trial. Ustekinumab-treated patients with clinical response, defined as a reduction in total Mayo score of 30% or more and 3 or more points from baseline with a reduction in their rectal bleeding subscore of 1 or more or a rectal bleeding subscore of 1 or less, at week 8 were deemed early responders and their outcomes were compared with delayed responders (week 8 nonresponders who subsequently responded at week 16). The primary outcome assessed was 1-year clinical remission, defined as a total Mayo score of 2 or less and no subscore greater than 1. RESULTS We included 642 ustekinumab-treated patients, including 321 (50%) early responders, 115 (17.9%) delayed responders, and 205 (32.1%) nonresponders. No differences were observed for 1-year clinical remission among early vs delayed responders (132 of 321 [41.1%] vs 40 of 115 [34.8%]; P = .233), or for other outcomes assessed regardless of induction dose. Compared with early responders, delayed responders had more severe baseline Mayo endoscopic disease (88 of 115 [76.5%] vs 206 of 321 [64.2%]; P = .015) and abnormal baseline C-reactive protein level greater than 3 mg/L (83 of 115 [72.2%] vs 183 of 321 [57%]; P = .004). Compared with nonresponders, delayed responders had a significant decrease in C-reactive protein level (F-value [degrees of freedom, mean squares] [4, 844]; P < .0001) and fecal calprotectin level (F[4, 818]; P < .0001) through week 16. CONCLUSIONS Compared with early ustekinumab responders, delayed responders had a greater inflammatory burden at baseline. Early and delayed responders had similar 1-year outcomes. Biomarker decline observed in delayed responders can help differentiate them from nonresponders.
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Affiliation(s)
- Emily C L Wong
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Parambir S Dulai
- Division of Gastroenterology, Northwestern University, Chicago, Illinois
| | - John K Marshall
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
| | - Vipul Jairath
- Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada
| | - Walter Reinisch
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Neeraj Narula
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
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Long-Term Outcomes of Early vs Delayed Responders to Vedolizumab and Adalimumab: A Post Hoc Analysis of the VARSITY Study. Am J Gastroenterol 2023; 118:121-128. [PMID: 36066459 DOI: 10.14309/ajg.0000000000001987] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 08/15/2022] [Indexed: 01/12/2023]
Abstract
INTRODUCTION It is uncertain whether patients with ulcerative colitis (UC) and delayed symptomatic response to therapy have as robust and durable a response as earlier responders to therapy. We compared clinical outcomes of early and delayed responders to vedolizumab and adalimumab for patients with moderate-severe UC. METHODS This was a post hoc analysis of the VARSITY study. Patients with early partial Mayo score (PMS) remission (PMS ≤1 at week 4/6 of therapy) were compared with those with delayed PMS remission (PMS ≤1 at week 14 and not week 4/6). Differences in proportions of patients achieving week 52 clinical remission (CR) (PMS = 0), endoscopic improvement (EI) (Mayo endoscopic subscore ≤1), and histoendoscopic mucosal improvement (HEMI) (Mayo endoscopic subscore ≤1 and Geboes score highest grade <3.2) were assessed. Confounders were adjusted for using multivariate logistic regression. RESULTS A total of 147 vedolizumab-treated and 110 adalimumab-treated patients attained early or late PMS remission. Those who attained early PMS remission with vedolizumab were more likely to attain week 52 CR than participants with delayed PMS remission with vedolizumab (69.1% [67/97] vs 50.0% [25/50], aOR 2.43 [95% CI 1.11-5.33], P = 0.027). Week 52 HEMI was more likely among early vedolizumab PMS remitters (63.9% [62/97] vs 40.0% [20/50], aOR 2.60 [95% CI 1.20-5.62], P = 0.015). Week 52 EI was similar between early and delayed PMS remitters to vedolizumab. No differences were observed in week 52 CR, EI, or HEMI between early and delayed PMS remitters to adalimumab. DISCUSSION Patients with UC who achieve early PMS remission with vedolizumab have greater odds of week 52 remission compared with delayed responders.
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Yang S, Yang S, Kwon Jo Y, Kim S, Jung Chang M, Choi J, Hee Cheon J, Yu YM. Efficacy and tolerability of infliximab retreatment in patients with inflammatory bowel disease: a systematic review and meta-analysis. Ther Adv Chronic Dis 2021; 12:20406223211041927. [PMID: 34729142 PMCID: PMC8438941 DOI: 10.1177/20406223211041927] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 08/03/2021] [Indexed: 11/30/2022] Open
Abstract
Background: A large proportion of patients with inflammatory bowel disease (IBD) relapse after drug discontinuation despite achieving a stable state of infliximab-induced clinical remission. Resuming the use of the same tumor necrosis factor-alpha (TNF-α) inhibitors in patients who relapse following TNF-α inhibitor discontinuation was suggested as a treatment strategy. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of infliximab retreatment in patients with IBD. Methods: A systematic literature search to shortlist relevant studies was conducted using the MEDLINE, Embase, CINAHL, and SCOPUS databases for studies published from inception to August 2020. Results: Nine studies were included in the meta-analysis. The pooled clinical remission rate of infliximab retreatment in patients with IBD was 85% (95% confidence interval (CI), 81–89%) for induction treatment and 73% (95% CI, 66–80%) for maintenance treatment. A clinical remission rate following infliximab reintroduction was achieved in a greater proportion of patients with Crohn’s disease (87%; 95% CI, 83–91%) than in those with ulcerative colitis (78%; 95% CI, 61–91%) for induction treatment, but the difference was not statistically significant. Infusion-related reactions after infliximab retreatment occurred in 9% of patients with IBD (95% CI, 3–16%). Conclusion: Infliximab retreatment showed high clinical remission rates with tolerable infusion-related reactions in patients with IBD who achieved remission with initial infliximab treatment but relapsed after its discontinuation. We suggest infliximab as a viable alternative in patients with IBD who previously responded well to infliximab treatment.
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Affiliation(s)
- Seungwon Yang
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea
| | - Siyoung Yang
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea
| | - Young Kwon Jo
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea
| | - Seungyeon Kim
- College of Pharmacy & Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea
| | - Min Jung Chang
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea
| | - Junjeong Choi
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Republic of Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea
| | - Yun Mi Yu
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, 85 Songdogwahak-ro, Yeonsu-gu, Incheon 21983, Republic of Korea
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Moreira Ferreira VF, Kimbrough DJ, Stankiewicz JM. A possible case of serum sickness after ocrelizumab infusion. Mult Scler 2020; 27:155-158. [DOI: 10.1177/1352458520910486] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
A 41-year-old female diagnosed with multiple sclerosis began ocrelizumab treatment. She received her first treatment course without significant complication. After receiving the first maintenance dose 6 months later, she developed weakness, myalgias, gastrointestinal symptoms, headache, and intermittent fever persisting for 4 weeks. A working diagnosis of serum sickness was determined after excluding other probable entities. She received 3 days of 1 g methylprednisolone intravenously and five plasma exchanges, experiencing gradual improvement. Serum sickness has occurred with monoclonal antibodies including rituximab. This case of possible ocrelizumab-associated serum sickness suggests that clinicians should remain vigilant about this possibility with this medication.
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Affiliation(s)
- Vanessa F Moreira Ferreira
- Department of Neurology, Brigham and Women’s Hospital, Partners MS Center, Harvard Medical School, Boston, MA, USA
| | - Dorlan J Kimbrough
- Department of Neurology, Brigham and Women’s Hospital, Partners MS Center, Harvard Medical School, Boston, MA, USA
| | - James M Stankiewicz
- Department of Neurology, Brigham and Women’s Hospital, Partners MS Center, Harvard Medical School, Boston, MA, USA
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Mori F, Saretta F, Bianchi A, Crisafulli G, Caimmi S, Liotti L, Bottau P, Franceschini F, Paglialunga C, Ricci G, Santoro A, Caffarelli C. Hypersensitivity Reactions to Monoclonal Antibodies in Children. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:232. [PMID: 32408641 PMCID: PMC7279169 DOI: 10.3390/medicina56050232] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 04/28/2020] [Accepted: 05/01/2020] [Indexed: 12/12/2022]
Abstract
Biologic drugs are widely used in pediatric medicine. Monoclonal antibodies (mAbs) in particular are a therapeutic option for rheumatic, autoinflammatory and oncologic diseases. Adverse drug reactions and hypersensitivity reactions (HSR) to mAbs may occur in children. Clinical presentation of HSRs to mAbs can be classified according to phenotypes in infusion-related reactions, cytokine release syndrome, both alpha type reactions and type I (IgE/non-IgE), type III, and type IV reactions, all beta-type reactions. The aim of this review is to focus on HSRs associated with the most frequent mAbs in childhood, with particular attention to beta-type reactions. When a reaction to mAbs is suspected a diagnostic work-up including in-vivo and in-vitro testing should be performed. A drug provocation test is recommended only when no alternative drugs are available. In selected patients with immediate IgE-mediated drug allergy a desensitization protocol is indicated. Despite the heavy use of mAbs in childhood, studies evaluating the reliability of diagnostic test are lacking. Although desensitization may be effective in reducing the risk of reactions in children, standardized pediatric protocols are still not available.
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Affiliation(s)
- Francesca Mori
- Allergy Unit, Meyer Children’s Hospital, 50139 Florence, Italy;
| | - Francesca Saretta
- SC Pediatria, Ospedale Latisana-Palmanova, Dipartimento Materno-Infantile Azienda Sanitaria Universitaria Friuli Centrale, 33057 Palmanova (UD), Italy;
| | | | - Giuseppe Crisafulli
- UO Allergologia, Dipartimento di Pediatria, Università di Messina, 98124 Messina, Italy;
| | - Silvia Caimmi
- Clinica Pediatrica Policlinico San Matteo, University di Pavia, 27100 Pavia, Italy;
| | - Lucia Liotti
- Pediatria, Ospedale Principi di Piemonte, 60019 Senigallia, Italy;
| | - Paolo Bottau
- Pediatria e Neonatologia, Ospedale di Imola, 40026 Imola, Italy;
| | - Fabrizio Franceschini
- UOC Pediatria, Azienda Ospedaliero-Universitaria “Ospedali Riuniti”, 60020 Ancona, Italy;
| | - Claudia Paglialunga
- UOC di Pediatria, Azienda Ospedaliera-Universitaria “Consorziale-Policlinico”, Ospedale Pediatrico Giovanni XXIII, 70123 Bari, Italy;
| | - Giampaolo Ricci
- Pediatric Unit, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy;
| | - Angelica Santoro
- Clinica Pediatrica, Dipartimento Medicina e Chirurgia, Università di Parma, 43126 Parma, Italy;
| | - Carlo Caffarelli
- Clinica Pediatrica, Dipartimento Medicina e Chirurgia, Università di Parma, 43126 Parma, Italy;
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Chiba M, Tsuji T, Nakane K, Obara Y, Komatsu M. Swift Efficacy with Infliximab 4 Years after Initial Standard Induction Therapy Followed by Severe Delayed Infusion Reaction in Crohn's Disease. Inflamm Bowel Dis 2020; 26:e4. [PMID: 31697829 DOI: 10.1093/ibd/izz273] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Affiliation(s)
- Mitsuro Chiba
- Division of Gastroenterology, Akita City Hospital, Akita City, Japan
| | - Tsuyotoshi Tsuji
- Division of Gastroenterology, Akita City Hospital, Akita City, Japan
| | - Kunio Nakane
- Division of Gastroenterology, Akita City Hospital, Akita City, Japan
| | - Yu Obara
- Division of Gastroenterology, Akita City Hospital, Akita City, Japan
| | - Masafumi Komatsu
- Division of Gastroenterology, Akita City Hospital, Akita City, Japan
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Soyer O, Demir S, Bilginer Y, Batu ED, Sonmez HE, Arıcı ZS, Şahiner ÜM, Sekerel BE, Ozen S. Severe hypersensitivity reactions to biological drugs in children with rheumatic diseases. Pediatr Allergy Immunol 2019; 30:833-840. [PMID: 31419311 DOI: 10.1111/pai.13114] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 07/16/2019] [Accepted: 07/25/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hypersensitivity reactions (HSR) to biologic drugs (BD) may limit their use in children with rheumatic diseases. We aimed to analyze the incidence and clinical characteristics of immediate type I (IgE/non-IgE) hypersensitivity reactions to BD and the risk factors for these reactions. METHODS Children with rheumatic diseases using BD who were evaluated in the pediatric allergy department for possible drug hypersensitivity reaction (DHR) due to BD or any other drug were included in the study. RESULTS One hundred and twenty-eight children (49.2% boys; 14.6 years [9.9-16.9 years] with juvenile idiopathic arthritis [58%], familial Mediterranean fever [14%], vasculitis [14%], and other diseases [14%]) had used eight different BD with 32 494 infusions/injections. Fifteen patients were evaluated for DHR [injection-site reactions [n = 4], adverse events [n = 2], drug hypersensitivity other than BD [n = 3], and immediate BD hypersensitivity [n = 6]). The incidence of immediate BD HSR was 4.7%, with a clinical presentation of anaphylaxis in 3.9% (tocilizumab [n = 3], rituximab [n = 2], positive skin test with culprit BD [n = 3]). Among patients with BD HSR, the median follow-up was longer (84.5 vs 54 months, P = .048), and renal (33.3% vs 4.1%, P = .002), hematologic involvement (16.7% vs 0, P < .001), and active disease (83.3% vs 13.9%, P < .001) were more common. Logistic regression analysis revealed that renal involvement, more than 14 hospitalizations per lifetime, and more than two different BD used were associated with BD hypersensitivity. CONCLUSION The frequency of severe immediate HSR due to BD was shown to be 3.9% in children with rheumatic diseases. Children with active rheumatic disease and who have exposure to multiple BD should be monitored for BD HSR, particularly during intravenous BD infusions.
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Affiliation(s)
- Ozge Soyer
- Department of Pediatrics, Division of Allergy, Hacettepe University School of Medicine, Ankara, Turkey
| | - Selcan Demir
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Yelda Bilginer
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Ezgi Deniz Batu
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Hafize Emine Sonmez
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Zehra Serap Arıcı
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
| | - Ümit Murat Şahiner
- Department of Pediatrics, Division of Allergy, Hacettepe University School of Medicine, Ankara, Turkey
| | - Bulent Enis Sekerel
- Department of Pediatrics, Division of Allergy, Hacettepe University School of Medicine, Ankara, Turkey
| | - Seza Ozen
- Department of Pediatrics, Division of Rheumatology, Hacettepe University School of Medicine, Ankara, Turkey
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11
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Matucci A, Nencini F, Maggi E, Vultaggio A. Hypersensitivity reactions to biologics used in rheumatology. Expert Rev Clin Immunol 2019; 15:1263-1271. [DOI: 10.1080/1744666x.2020.1684264] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Andrea Matucci
- Immunoallergology Unit, Department of Medicine and Geriatrics, Careggi University Hospital, Florence, Italy
| | - Francesca Nencini
- Immunoallergology Unit, Department of Medicine and Geriatrics, Careggi University Hospital, Florence, Italy
| | - Enrico Maggi
- Translational Immunology Unit, Immunology Area, Pediatric Hospital Bambino Gesù, I.R.C.C.S., Rome, Italy
| | - Alessandra Vultaggio
- Immunoallergology Unit, Department of Medicine and Geriatrics, Careggi University Hospital, Florence, Italy
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Inui K, Koike T, Tada M, Sugioka Y, Okano T, Mamoto K, Sakawa A, Fukushima K, Nakamura H. Clinical and radiologic analysis of on-demand use of etanercept for disease flares in patients with rheumatoid arthritis for 2 years: The RESUME study: A case-control study. Medicine (Baltimore) 2018; 97:e12462. [PMID: 30235736 PMCID: PMC6160256 DOI: 10.1097/md.0000000000012462] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
To reduce costs of biological disease-modifying antirheumatic drugs (bDMARDs), we evaluated the efficacy of repeated etanercept (ETN) discontinuation and restarting in rheumatoid arthritis (RA) patients in a case-control study.Thirty-one bDMARD-naive RA patients with moderate to high disease activity received ETN until low disease activity (LDA) was achieved, after which ETN was discontinued. Upon flaring, ETN was readministered with observation every 2 months for 2 years, and radiographically evaluated in comparison with a historical control group treated continuously with ETN. Statistical methods including Fisher exact test, analysis of variance (ANOVA), Kruskal-Wallis test, multiple regression analysis, and Student t test were conducted as appropriate.Thirteen patients with inadequate response to ETN were withdrawn from the study, and 5 had no flare-up after ETN discontinuation. In the remaining 13 patients, ETN was used on-demand to maintain LDA. Multivariate analysis revealed that MTX was significantly correlated with ETN. All 13 patients achieved LDA at final follow-up. Although joint damage progressed in patients using ETN on-demand, structural damage progression in the on-demand group was not significantly different from that in controls.On-demand use of ETN for flaring reduced disease activity but not structural damage in 50% of patients (though not significantly). However, inhibition of joint damage was achieved in 50% of patients after 2 years, supporting on-demand use of ETN as a treatment option for patients with RA who cannot afford bDMARD or targeted synthetic DMARD therapy.
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Affiliation(s)
- Kentaro Inui
- Department of Rheumatosurgery
- Department of Orthopaedic Surgery
| | - Tatsuya Koike
- Center for Senile Degenerative Disorders, Osaka City University Medical School, Abeno-ku, Osaka
- Search Institute for Bone and Arthritis Disease (SINBAD), Shirahama Foundation for Health and Welfare, Shirahama-cho, Wakayama
| | - Masahiro Tada
- Department of Orthopaedic Surgery, Osaka City General Hospital, Miyakojima-ku
| | - Yuko Sugioka
- Center for Senile Degenerative Disorders, Osaka City University Medical School, Abeno-ku, Osaka
| | | | | | - Akira Sakawa
- Department of Orthopaedic Surgery, Osaka City Juso Hospital, Yodogawa-ku
| | - Kenzo Fukushima
- Orthopaedic Surgery, Fujiidera Municipal Hospital, Fujiidera City, Osaka, Japan
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Lew D, Yoon SM, Yan X, Robbins L, Haritunians T, Liu Z, Li D, McGovern DPB. Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients. World J Gastroenterol 2017; 23:7265-7273. [PMID: 29142473 PMCID: PMC5677193 DOI: 10.3748/wjg.v23.i40.7265] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Revised: 08/25/2017] [Accepted: 09/13/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations.
METHODS This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer’s protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure.
RESULTS Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients (21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the anti-TNF agent. In total: n = 66 (5%) infusion reactions; n = 49 (4%) allergic/serum sickness reactions; n = 19 (1.5%) lupus-like reactions, n = 52 (4%) rash, n = 18 (1.4%) infections. In Crohn’s disease, IgA ASCA (P = 0.04) and IgG-ASCA (P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions (P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT (Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event.
CONCLUSION Our study shows 1 in 5 IBD patients experience an adverse event to anti-TNF therapy with novel serologic, genetic , and pathways associations.
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Affiliation(s)
- Daniel Lew
- Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Soon Man Yoon
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Xiaofei Yan
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Lori Robbins
- Department of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Talin Haritunians
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Zhenqiu Liu
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Dalin Li
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Dermot PB McGovern
- F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
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Premedication Use in Preventing Acute Infliximab Infusion Reactions in Patients with Inflammatory Bowel Disease: A Single Center Cohort Study. Inflamm Bowel Dis 2017; 23:1882-1889. [PMID: 28837521 DOI: 10.1097/mib.0000000000001189] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Infliximab (IFX) is commonly used in patients with inflammatory bowel disease. One common side effect of IFX is an acute infusion reaction. Despite the lack of evidence supporting their use, clinicians use various premedications to prevent acute reactions. We evaluated the effectiveness of premedications in the prevention of acute IFX infusion reactions. METHODS A retrospective cohort study was performed identifying patients with a diagnosis of inflammatory bowel disease who received IFX at our institution. Information about each IFX infusion was recorded, including the dose, infusion rate, use of premedications, and any reactions. Infusions were stratified into low and high risk. In the high- and low-risk groups, the relative risk was calculated for each premedication combination used in our institution. RESULTS Seven hundred seventy-three patients were identified; 578 patients (7090 infusions) met inclusion criteria and were included for analysis. Nine hundred eighty-six high-risk infusions were isolated; 620 (62.8%) of these infusions were administered with premedications (diphenhydramine and/or hydrocortisone) and 53 (5.4%) reactions occurred. Six thousand one hundred four low-risk infusions were identified; 2253 (36.9%) of these infusions had premedications and 61 (1.0%) reactions occurred. In both groups, none of the premedications used resulted in a significantly lower reaction rate compared with no premedication use. CONCLUSIONS In both the high- and low-risk cohorts in this study, premedication use was not effective in reducing the rate of acute IFX reactions. Given this, routine premedication use is not recommended without future randomized control trials to demonstrate efficacy.
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Abstract
INTRODUCTION In most European countries, an infliximab biosimilar (CT-P13) is currently in common use. In vitro and in vivo studies have proved a high similarity between CT-P13 and the reference infliximab. CT-P13 was licensed for use in patients with Crohn disease (CD) based on the extrapolation of data from preclinical studies and clinical trials in rheumatology indications. The aim of this study was to assess the similarity between CT-P13 and the originator infliximab in induction therapy in CD paediatric patients. METHODS Thirty-six CD paediatric patients from 3 Polish academic centres who started biological therapy with CT-P13 were enrolled in this prospective, observational study. Patients received 3 induction doses (5 mg/kg) of CT-P13 at weeks 0, 2, 6. Assessment was performed before the first infusion and at week 14. RESULTS Overall 34/36 (94.4%) patients completed induction therapy with CT-P13. A clinical response or remission after 3 initial doses was achieved in 31/36 (86%) and 24/36 (67%) of patients, respectively. Clinically and statistically significant decreases in Paediatric Crohn's Disease Activity Index, C-reactive protein, and erythrocyte sedimentation rate were observed in the responders group. An allergic reaction during infusion, which led to treatment discontinuation, was observed in one case. CONCLUSIONS Induction therapy with CT-P13 in children with CD is effective. The profile appears similar to that reported for the reference infliximab. No unexpected adverse events occurred.
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16
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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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17
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Strik AS, Bots SJA, D’Haens G, Löwenberg M. Optimization of anti-TNF therapy in patients with Inflammatory Bowel Disease. Expert Rev Clin Pharmacol 2016; 9:429-39. [DOI: 10.1586/17512433.2016.1133288] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Lichtenstein L, Ron Y, Kivity S, Ben-Horin S, Israeli E, Fraser GM, Dotan I, Chowers Y, Confino-Cohen R, Weiss B. Infliximab-Related Infusion Reactions: Systematic Review. J Crohns Colitis 2015; 9:806-15. [PMID: 26092578 PMCID: PMC4558633 DOI: 10.1093/ecco-jcc/jjv096] [Citation(s) in RCA: 171] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2014] [Revised: 05/11/2015] [Accepted: 05/17/2015] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur. METHODS We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients. RESULTS We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies. CONCLUSIONS There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms.
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Affiliation(s)
- Lev Lichtenstein
- Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
| | - Yulia Ron
- Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
| | - Shmuel Kivity
- Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
| | - Shomron Ben-Horin
- Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
| | - Eran Israeli
- Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Gerald M Fraser
- Rabin Medical Center, Petach Tikva, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
| | - Iris Dotan
- Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
| | - Yehuda Chowers
- Rambam Health Care Campus, Haifa, Israel; Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel
| | - Ronit Confino-Cohen
- Meir Medical Center, Kfar Saba, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
| | - Batia Weiss
- Edmond and Lily Safra Children's Hospital, Tel Hashomer, Israel; Sackler Faculty of Medicine, University of Tel Aviv, Israel
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19
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Sehgal VN, Pandhi D, Khurana A. Biologics in dermatology: adverse effects. Int J Dermatol 2015; 54:1442-60. [PMID: 26147909 DOI: 10.1111/ijd.12802] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2013] [Revised: 01/13/2014] [Accepted: 06/25/2014] [Indexed: 12/13/2022]
Abstract
Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner.
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Affiliation(s)
- Virendra N Sehgal
- Dermato-Venereology (Skin/VD) Center, Sehgal Nursing Home, Delhi, India
| | - Deepika Pandhi
- Department of Dermatology and STD, University College of Medical Sciences, and Associated Guru Teg Bahadur Hospital, Shahdara, Delhi, India
| | - Ananta Khurana
- Department of Dermatology and STD, Dr RML hospital and PGIMER, New Delhi, India
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20
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Factors influencing acute infusion reactions in inflammatory bowel disease patients treated with infliximab in the era of scheduled maintenance therapy. Eur J Gastroenterol Hepatol 2015; 27:705-11. [PMID: 25856689 DOI: 10.1097/meg.0000000000000354] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND An acute infusion reaction during infliximab infusions could lead to drug withdrawal and limit the therapeutic armamentarium in inflammatory bowel diseases. AIM To determine the risk and protective factors of an acute infusion reaction. MATERIALS AND METHODS Data were retrieved retrospectively from electronic charts of patients from the 'Clermont-Ferrand IBD cohort'. RESULTS Among 80 patients, including 51 (63.8%) patients with Crohn's disease, 23 (28.8%) experienced an acute infusion reaction. In multivariate analysis, the Crohn's disease nonstricturing nonfistulizing phenotype predicted an acute infusion reaction (odds ratio=11.40, 95% confidence interval 1.5-87.6; P=0.019).Among 1107 infusions, we observed 38 acute infusion reactions (3.4%). In multivariate analysis, only resumption of infliximab after drug holiday was a major risk factor (odds ratio=24.87, 95% confidence interval 4.4-140.0; P<0.001). Concomitant premedication or immunosuppressant therapies did not prevent an acute infusion reaction.The patients who experienced an acute infusion reaction had a trend toward a higher rate of infliximab discontinuation (69.6 vs. 50.9%, P=0.14). CONCLUSION An acute infusion reaction is a major event in the history of inflammatory bowel diseases patients treated with infliximab as it could lead to drug discontinuation and thus limits the therapeutic armamentarium considerably. The resumption of infliximab after drug holiday is a major risk factor for an acute infusion reaction. Premedication efficacy remains questionable and should be limited to these high-risk patients.
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21
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Vultaggio A, Nencini F, Pratesi S, Petroni G, Maggi E, Matucci A. Manifestations of Antidrug Antibodies Response: Hypersensitivity and Infusion Reactions. J Interferon Cytokine Res 2014; 34:946-952. [PMID: 25493962 DOI: 10.1089/jir.2012.0139] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Immunogenicity of biological agents leads to the development of antidrug antibodies (ADA) and it may be associated to hypersensitivity reactions. Immediate infusion reactions occur during or within 1 h after infusion, and their clinical manifestations vary considerably, ranging from mild to severe and life-threatening. Recent studies show that different mechanisms sustain hypersensitivity reactions toward biologics, and the application of novel methods for detecting ADA has demonstrated the involvement of specific IgE isotypes. Considering the severity of the reactions, it is important for clinicians to recognize their symptoms, to know their pathophysiological mechanisms, and to take risk assessment and prophylactic procedures. This review summarizes the clinical manifestations of antibody and nonantibody-mediated reactions as well as the humoral and cellular mechanisms of antidrug responses. Last, the management of patients at risk is discussed. The definition of diagnostic and prophylactic strategies represents an unavoidable need in the management of potentially reactive patients to improve the safety profile of biologics.
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Affiliation(s)
- Alessandra Vultaggio
- 1 Immunoallergology Unit, Department of Biomedicine, Azienda Ospedaliero-Universitaria Careggi , Florence, Italy
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22
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Ruemmele FM, Veres G, Kolho KL, Griffiths A, Levine A, Escher JC, Amil Dias J, Barabino A, Braegger CP, Bronsky J, Buderus S, Martín-de-Carpi J, De Ridder L, Fagerberg UL, Hugot JP, Kierkus J, Kolacek S, Koletzko S, Lionetti P, Miele E, Navas López VM, Paerregaard A, Russell RK, Serban DE, Shaoul R, Van Rheenen P, Veereman G, Weiss B, Wilson D, Dignass A, Eliakim A, Winter H, Turner D. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease. J Crohns Colitis 2014; 8:1179-1207. [PMID: 24909831 DOI: 10.1016/j.crohns.2014.04.005] [Citation(s) in RCA: 838] [Impact Index Per Article: 76.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Revised: 04/14/2014] [Accepted: 04/14/2014] [Indexed: 02/07/2023]
Abstract
Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.
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Affiliation(s)
- F M Ruemmele
- Department of Paediatric Gastroenterology, APHP Hôpital Necker Enfants Malades, 149 Rue de Sèvres 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 2 Rue de l'École de Médecine, 75006 Paris, France; INSERM U989, Institut IMAGINE, 24 Bd Montparnasse, 75015 Paris, France.
| | - G Veres
- Department of Paediatrics I, Semmelweis University, Bókay János str. 53, 1083 Budapest, Hungary
| | - K L Kolho
- Department of Gastroenterology, Helsinki University Hospital for Children and Adolescents, Stenbäckinkatu 11, P.O. Box 281, 00290 Helsinki, Finland
| | - A Griffiths
- Department of Paediatrics, Hospital for Sick Children, University of Toronto, 555 University Avenue, M5G 1X8 Toronto, ON, Canada
| | - A Levine
- Paediatric Gastroenterology and Nutrition Unit, Tel Aviv University, Edith Wolfson Medical Center, 62 HaLohamim Street, 58100 Holon, Israel
| | - J C Escher
- Department of Paediatric Gastroenterology, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Netherlands
| | - J Amil Dias
- Unit of Paediatric Gastroenterology, Hospital S. João, A Hernani Monteiro, 4202-451, Porto, Portugal
| | - A Barabino
- Gastroenterology and Endoscopy Unit, Istituto G. Gaslini, Via G. Gaslini 5, 16148 Genoa, Italy
| | - C P Braegger
- Division of Gastroenterology and Nutrition, and Children's Research Center, University Children's Hospital Zurich, Steinwiesstrasse 75, 8032 Zurich, Switzerland
| | - J Bronsky
- Department of Pediatrics, University Hospital Motol, Uvalu 84, 150 06 Prague, Czech Republic
| | - S Buderus
- Department of Paediatrics, St. Marien Hospital, Robert-Koch-Str.1, 53115 Bonn, Germany
| | - J Martín-de-Carpi
- Department of Paediatric Gastroenterolgoy, Hepatology and Nutrition, Hospital Sant Joan de Déu, Paseo Sant Joan de Déu 2, 08950 Barcelona, Spain
| | - L De Ridder
- Department of Paediatric Gastroenterology, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, Netherlands
| | - U L Fagerberg
- Department of Pediatrics, Centre for Clinical Research, Entrance 29, Västmanland Hospital, 72189 Västerås/Karolinska Institutet, Stockholm, Sweden
| | - J P Hugot
- Department of Gastroenterology and Nutrition, Hopital Robert Debré, 48 Bd Sérurier, APHP, 75019 Paris, France; Université Paris-Diderot Sorbonne Paris-Cité, 75018 Paris France
| | - J Kierkus
- Department of Gastroenterology, Hepatology and Feeding Disorders, Instytut Pomnik Centrum Zdrowia Dziecka, Ul. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - S Kolacek
- Department of Paediatric Gastroenterology, Children's Hospital, University of Zagreb Medical School, Klaićeva 16, 10000 Zagreb, Croatia
| | - S Koletzko
- Department of Paediatric Gastroenterology, Dr. von Hauner Children's Hospital, Lindwurmstr. 4, 80337 Munich, Germany
| | - P Lionetti
- Department of Gastroenterology and Nutrition, Meyer Children's Hospital, Viale Gaetano Pieraccini 24, 50139 Florence, Italy
| | - E Miele
- Department of Translational Medical Science, Section of Paediatrics, University of Naples "Federico II", Via S. Pansini, 5, 80131 Naples, Italy
| | - V M Navas López
- Paediatric Gastroenterology and Nutrition Unit, Hospital Materno Infantil, Avda. Arroyo de los Ángeles s/n, 29009 Málaga, Spain
| | - A Paerregaard
- Department of Paediatrics 460, Hvidovre University Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark
| | - R K Russell
- Department of Paediatric Gastroenterology, Yorkhill Hospital, Dalnair Street, Glasgow G3 8SJ, United Kingdom
| | - D E Serban
- 2nd Department of Paediatrics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Emergency Children's Hospital, Crisan nr. 5, 400177 Cluj-Napoca, Romania
| | - R Shaoul
- Department of Pediatric Gastroenterology and Nutrition, Rambam Health Care Campus Rappaport Faculty Of Medicine, 6 Ha'alya Street, P.O. Box 9602, 31096 Haifa, Israel
| | - P Van Rheenen
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, University Medical Center Groningen, P.O. Box 30001, 9700 RB Groningen, Netherlands
| | - G Veereman
- Department of Paediatric Gastroenterology and Nutrition, Children's University Hospital, Laarbeeklaan 101, 1090 Brussels, Belgium
| | - B Weiss
- Paediatric Gastroenterology and Nutrition Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, 52625 Tel Hashomer, Israel
| | - D Wilson
- Child Life and Health, Paediatric Gastroenterology, Royal Hospital for Sick Children, 9 Sciennes Road, Edinburgh EH9 1LF, United Kingdom
| | - A Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Wilhelm-Epstein-Str. 4, 60431 Frankfurt/Main, Gemany
| | - A Eliakim
- 33-Gastroenterology, Sheba Medical Center, 52621 Tel Hashomer, Israel
| | - H Winter
- Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Mass General Hospital for Children, 175 Cambridge Street, 02114 Boston, United States
| | - D Turner
- Pediatric Gastroenterology Unit, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel
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23
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Feuerstein JD, Cheifetz AS. Miscellaneous adverse events with biologic agents (excludes infection and malignancy). Gastroenterol Clin North Am 2014; 43:543-563. [PMID: 25110258 DOI: 10.1016/j.gtc.2014.05.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Anti-tumor necrosis factor-α (anti-TNF) agents are frequently used in the treatment of inflammatory bowel disease (IBD). Currently, there are 4 anti-TNF therapies that are Food and Drug Administration-approved for moderate to severe IBD: infliximab, adalimumab, golimumab, and certolizumab pegol. For most noninfectious, nonmalignant adverse events, cessation of anti-TNF therapy typically leads to improvement or resolution of drug-induced complications. In this article, the current knowledge regarding the noninfectious and nonmalignant toxicities associated with anti-TNF agents is summarized.
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Affiliation(s)
- Joseph D Feuerstein
- Division of Gastroenterology, Department of Medicine, Center for Inflammatory Bowel Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Rabb 425, Boston, MA 02215, USA
| | - Adam S Cheifetz
- Division of Gastroenterology, Department of Medicine, Center for Inflammatory Bowel Diseases, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Rabb 425, Boston, MA 02215, USA.
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24
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Rojko JL, Evans MG, Price SA, Han B, Waine G, DeWitte M, Haynes J, Freimark B, Martin P, Raymond JT, Evering W, Rebelatto MC, Schenck E, Horvath C. Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes. Toxicol Pathol 2014; 42:725-64. [DOI: 10.1177/0192623314526475] [Citation(s) in RCA: 102] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Vascular inflammation, infusion reactions, glomerulopathies, and other potentially adverse effects may be observed in laboratory animals, including monkeys, on toxicity studies of therapeutic monoclonal antibodies and recombinant human protein drugs. Histopathologic and immunohistochemical (IHC) evaluation suggests these effects may be mediated by deposition of immune complexes (ICs) containing the drug, endogenous immunoglobulin, and/or complement components in the affected tissues. ICs may be observed in glomerulus, blood vessels, synovium, lung, liver, skin, eye, choroid plexus, or other tissues or bound to neutrophils, monocytes/macrophages, or platelets. IC deposition may activate complement, kinin, and/or coagulation/fibrinolytic pathways and result in a systemic proinflammatory response. IC clearance is biphasic in humans and monkeys (first from plasma to liver and/or spleen, second from liver or spleen). IC deposition/clearance is affected by IC composition, immunomodulation, and/or complement activation. Case studies are presented from toxicity study monkeys or rats and indicate IHC-IC deposition patterns similar to those predicted by experimental studies of IC-mediated reactions to heterologous protein administration to monkeys and other species. The IHC-staining patterns are consistent with findings associated with generalized and localized IC-associated pathology in humans. However, manifestations of immunogenicity in preclinical species are generally not considered predictive to humans.
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Affiliation(s)
| | | | - Shari A. Price
- Charles River Pathology Associates, Frederick, Maryland, USA
| | - Bora Han
- Pfizer, Inc, San Diego, California, USA
| | - Gary Waine
- CSL Limited, Parkville, Melbourne, Australia
| | | | - Jill Haynes
- CSL Limited, Parkville, Melbourne, Australia
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25
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Hwang SH, Yoo HS, Yoon MK, Park HS. Detection of IgE binding component to infliximab in a patient with infliximab-induced anaphylaxis. Ann Allergy Asthma Immunol 2014; 112:393-4. [PMID: 24583135 DOI: 10.1016/j.anai.2014.02.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 02/05/2014] [Accepted: 02/05/2014] [Indexed: 11/29/2022]
Affiliation(s)
- Sun Hyuk Hwang
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea
| | - Hye-Soo Yoo
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea
| | - Moon Kyung Yoon
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea
| | - Hae-Sim Park
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
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26
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Koike R, Takeuchi T, Eguchi K, Miyasaka N. Update on the Japanese guidelines for the use of infliximab and etanercept in rheumatoid arthritis. Mod Rheumatol 2014. [DOI: 10.3109/s10165-007-0626-3] [Citation(s) in RCA: 96] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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27
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Sagawa A. The efficacy and safety of reinstitution of tocilizumab in patients with relapsed active rheumatoid arthritis after long-term withdrawal of tocilizumab. Mod Rheumatol 2014. [DOI: 10.3109/s10165-011-0419-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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28
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Abstract
: Anti-tumor necrosis factor agents are now considered to be a vital component of the treatment algorithm for pediatric inflammatory bowel disease. Despite the clear benefit of these agents and the realignment of treatment goals to achieve early mucosal healing, the decision to initiate therapy is often delayed due to uncertainties regarding risks and benefits. The purpose of this review was to summarize the currently available data regarding anti-tumor necrosis factor agents in pediatric inflammatory bowel disease. Specifically, we review their expected efficacy in both Crohn's disease and ulcerative colitis and the likelihood of side effects associated with these agents. In addition, we address the barriers physicians face when communicating these data and help to identify how pediatric patients and their parents can be more involved in a shared decision-making process. Through the creation of a new decision aid (Option Grid), we hope to allow for a more clear line of communication at the bedside when helping patients and parents make these difficult treatment decisions.
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29
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Adjunctive treatment to antitumor necrosis factor in pediatric patients with refractory Crohn's disease. Curr Opin Pediatr 2013; 25:624-8. [PMID: 23995433 DOI: 10.1097/mop.0b013e328364df22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW The use of antitumor necrosis factor (anti-TNF) agents to treat Crohn's disease in children has become quite common over the past decade. There are incomplete data to guide the clinician in choosing whether adjunctive therapy should be added to optimize response to these drugs. RECENT FINDINGS Addition of immunomodulators such as thiopurines or possibly methotrexate can increase anti-TNF drug levels, reduce the risk of antidrug antibodies, and improve response. This is tempered by the reports of younger patients developing hepato-splenic T-cell lymphoma while taking thiopurines with and without concomitant anti-TNF medications. The available data are reviewed including recent pediatric reports. SUMMARY The addition of immunomodulators to anti-TNF therapies can optimize their performance. Careful discussion of the risks and side-effects must be undertaken when considering this approach. Additional knowledge is required to stratify which children with inflammatory bowel disease need this approach, and/or who are at risk for significant complications.
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30
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Grosen A, Julsgaard M, Christensen LA. Serum sickness-like reaction due to Infliximab reintroduction during pregnancy. J Crohns Colitis 2013; 7:e191. [PMID: 23102649 DOI: 10.1016/j.crohns.2012.10.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2012] [Accepted: 10/08/2012] [Indexed: 02/06/2023]
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Bradley GM, Oliva-Hemker M. Infliximab for the treatment of pediatric ulcerative colitis. Expert Rev Gastroenterol Hepatol 2012; 6:659-65. [PMID: 23237250 DOI: 10.1586/egh.12.53] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Ulcerative colitis is a chronic, idiopathic, inflammatory disease of the colon and rectum that may be associated with growth failure, nutritional derangements and psychosocial ramifications in affected children. Multiple medical options are available to achieve disease remission; however, some of these medications can have unwanted side effects, especially in younger patients. With increased understanding of the etiology of the disease, newer therapeutic alternatives have arisen in the form of biologic therapies, namely monoclonal antibodies targeted to a specific protein or receptor. Specifically, infliximab, an anti-TNF-α agent, has been shown to be safe and effective for the treatment of moderate-to-severe pediatric ulcerative colitis.
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Affiliation(s)
- Gia M Bradley
- Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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32
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de Bie CI, Escher JC, de Ridder L. Antitumor necrosis factor treatment for pediatric inflammatory bowel disease. Inflamm Bowel Dis 2012; 18:985-1002. [PMID: 21936033 DOI: 10.1002/ibd.21871] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2011] [Accepted: 07/29/2011] [Indexed: 12/14/2022]
Abstract
Infliximab, adalimumab, and certolizumab are monoclonal antibodies against tumor necrosis factor-α (TNFα), a proinflammatory cytokine with an increased expression in the inflamed tissues of inflammatory bowel disease (IBD) patients. Currently, infliximab is the only anti-TNF drug that has been approved for use in refractory pediatric Crohn's disease (CD). Nevertheless, adalimumab and certolizumab have been used off-label to treat refractory pediatric IBD. Over the past 10 years, anti-TNF treatment has been of great benefit to many pediatric IBD patients, but their use is not without risks (infections, autoimmune diseases, malignancies). Despite the growing experience with these drugs in children with IBD, optimal treatment strategies still need to be determined. The purpose of this review is to summarize the current knowledge on the use of anti-TNF drugs in pediatric IBD and to discuss the yet-unsolved issues.
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Affiliation(s)
- Charlotte I de Bie
- Department of Pediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands
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34
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Pizarro TT, Pastorelli L, Bamias G, Garg RR, Reuter BK, Mercado JR, Chieppa M, Arseneau KO, Ley K, Cominelli F. SAMP1/YitFc mouse strain: a spontaneous model of Crohn's disease-like ileitis. Inflamm Bowel Dis 2011; 17:2566-2584. [PMID: 21557393 PMCID: PMC3154989 DOI: 10.1002/ibd.21638] [Citation(s) in RCA: 143] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2010] [Accepted: 01/03/2011] [Indexed: 12/18/2022]
Abstract
The SAMP1/YitFc mouse strain represents a model of Crohn's disease (CD)-like ileitis that is ideal for investigating the pathogenesis of chronic intestinal inflammation. Different from the vast majority of animal models of colitis, the ileal-specific phenotype characteristic of SAMP1/YitFc mice occurs spontaneously, without genetic, chemical, or immunological manipulation. In addition, SAMP1/YitFc mice possess remarkable similarities to the human condition with regard to disease location, histologic features, incidence of extraintestinal manifestations, and response to conventional therapies. SAMP1/YitFc mice also display a well-defined time course of a predisease state and phases of acute and chronic ileitis. As such, the SAMP1/YitFc model is particularly suitable for elucidating pathways that precede the clinical phenotype that may lead to preventive, and therefore more efficacious, intervention with the natural course of disease, or alternatively, for the development of therapeutic strategies directed against chronic, established ileitis. In this review we summarize important contributions made by our group and others that uncover potential mechanisms in the pathogenesis of CD using this unique murine model of chronic intestinal inflammation.
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Affiliation(s)
- Theresa T Pizarro
- Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
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35
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Dotson J, Crandall W, Bout-Tabaku S. Exploring the differential diagnosis of joint complaints in pediatric patients with inflammatory bowel disease. Curr Gastroenterol Rep 2011; 13:271-8. [PMID: 21298374 DOI: 10.1007/s11894-011-0181-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
About one quarter of children with inflammatory bowel disease (IBD) experience an extraintestinal manifestation, with the most common being arthritis or arthralgia. Because of the frequency of these joint complaints and their effect on quality of life, it is important to consider all possible etiologies in order to promptly evaluate, diagnose, and possibly refer to other specialists. Pediatric gastroenterologist and IBD specialists are cognizant of the extraintestinal joint manifestations, but may be less familiar with rheumatic disease and the musculoskeletal examination. We explore the differential diagnosis of joint complaints in children, with a focus on IBD-related disease and rheumatic disease.
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Affiliation(s)
- Jennifer Dotson
- Division of Pediatric Gastroenterology, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
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36
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Incidence of acute severe infusion reactions to infliximab depends on definition used rather than assay: authors’ reply. Aliment Pharmacol Ther 2011. [DOI: 10.1111/j.1365-2036.2011.04748.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/25/2023]
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37
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Steenholdt C, Svenson M, Bendtzen K, Thomsen OØ, Brynskov J, Ainsworth MA. Severe infusion reactions to infliximab: aetiology, immunogenicity and risk factors in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2011; 34:51-8. [PMID: 21535447 DOI: 10.1111/j.1365-2036.2011.04682.x] [Citation(s) in RCA: 122] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Infliximab (IFX) elicits acute severe infusion reactions in about 5% of patients with inflammatory bowel disease (IBD). AIM To investigate the role of anti-IFX antibodies (Ab) and other risk factors. METHODS The study included all IBD patients treated with IFX at a Danish university hospital until 2010 either continuously (IFX every 4-12 weeks) or episodically (reinitiation after >12 weeks). Anti-IFX Ab were measured using radioimmunoassay. RESULTS Twenty-five (8%) of 315 patients experienced acute severe infusion reactions. Univariate analysis showed that patients who reacted were younger at the time of diagnosis (19 vs. 26 years, P=0.013) and at first IFX infusion (28 vs. 35 years, P=0.012). Furthermore, they more often received episodic therapy (72% vs. 31%, P<0.001) and logistic regression revealed this as the only significant predictor of reactions (OR 5 [2-13]; P<0.001). IFX reinitiation after 6 months intermission further increased the risk (OR 8 [3-20], P<0.001). Most reactions (n=14, 88%) occurred at 2nd infusion in the 2nd treatment series (P=0.006). Anti-IFX IgG Ab were highly positive in 19 of 20 patients (95%) shortly after the reactions (median 84 U/mL). Anti-IFX IgG Ab measured prior to the retreatment series were negative in 7 of 11 patients tested (64%). Anti-IFX IgE Ab were negative in all patients with reactions. CONCLUSIONS Acute severe infusion reactions were strongly associated with development of anti-IFX IgG Ab, but not with anti-IFX IgE Ab. The risk was particularly high at the 2nd infusion in retreatment series. Negative anti-IFX Ab before reinitiation did not rule out reactions.
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Affiliation(s)
- C Steenholdt
- Department of Medical Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev, Denmark.
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38
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Maggi E, Vultaggio A, Matucci A. Acute infusion reactions induced by monoclonal antibody therapy. Expert Rev Clin Immunol 2011; 7:55-63. [PMID: 21162650 DOI: 10.1586/eci.10.90] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
This article reports recent evidence on epidemiological data concerning monoclonal antibody (mAb) infusion-related anaphylaxis, as well as recent data on the correlation between mAb immunogenicity and safety profiles. Pathogenic mechanisms of mAb-related adverse reactions including hypersensitivity, IgE- and non-IgE-mediated events and cytokine release syndrome are also highlighted. Finally, the role of serum anti-mAb antibodies as markers to monitor the safety of such therapeutical compounds are extensively evaluated. The anaphylaxis occurring during therapy with the anti-TNF-α mAb infliximab, largely used in immune-mediated diseases, has been taken as a paradigm.
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Affiliation(s)
- Enrico Maggi
- Center for Research, Transfer and High Education DENOTHE, University of Florence, Policlinico di Careggi, Viale Morgagni 85, 50134 Florence, Italy.
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39
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Sagawa A. The efficacy and safety of reinstitution of tocilizumab in patients with relapsed active rheumatoid arthritis after long-term withdrawal of tocilizumab: retreatment of patients with rheumatoid arthritis with novel anti-IL-6 receptor antibody after a long-term interval following SAMURAI: the RONIN study. Mod Rheumatol 2011; 21:352-8. [PMID: 21347804 DOI: 10.1007/s10165-011-0419-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Accepted: 12/28/2010] [Indexed: 11/30/2022]
Abstract
We have evaluated the efficacy and safety of tocilizumab (TCZ) re-administration in patients with active rheumatoid arthritis (RA) who had previously received TCZ treatment for about 31 months. Four patients whose RA had been well-controlled with 8 mg/kg TCZ treatment every 4 weeks and had withdrawn from the treatment were enrolled. They resumed TCZ treatment after TCZ was authorized for RA treatment in Japan. Disease activity was assessed by the Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR), and synovitis in the wrists and elbows was measured by ultrasonography at baseline and during follow-up. The mean DAS28-ESR was 6.32 before the first TCZ infusion. After fewer than 20 months of initial TCZ treatment, the mean DAS28-ESR decreased to 1.87. However, after withdrawal of TCZ treatment, the disease activity could not be sufficiently controlled with conventional disease-modifying antirheumatic drugs or biologic agents. The maximum interval between TCZ treatments was approximately 34 months. Following reinstatement of the TCZ treatment, within 12 months the mean DAS28-ESR improved from 5.21 to 2.87, with the synovitis in the wrists and elbow joints also showing great improvement. These findings demonstrate that TCZ retreatment in active RA patients who had relapsed after long-term discontinuation of TCZ treatment led to an improvement in the signs and symptoms of RA and in synovitis without any severe adverse events.
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Affiliation(s)
- Akira Sagawa
- Sagawa Akira Rheumatology Clinic, Pacific Marks Sapporo Kita-Ichijo 5F, Kita-1, Nishi-7, Chuo-ku, Sapporo, Hokkaido, 060-0001, Japan.
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Miehsler W, Novacek G, Wenzl H, Vogelsang H, Knoflach P, Kaser A, Dejaco C, Petritsch W, Kapitan M, Maier H, Graninger W, Tilg H, Reinisch W. A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease. J Crohns Colitis 2010; 4:221-56. [PMID: 21122513 DOI: 10.1016/j.crohns.2009.12.001] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2009] [Accepted: 12/01/2009] [Indexed: 12/15/2022]
Abstract
Infliximab (IFX) has tremendously enriched the therapy of inflammatory bowel diseases (IBD) and other immune mediated diseases. Although the efficacy of IFX was undoubtedly proven during the last decade numerous publications have also caused various safety concerns. To summarize the immense information concerning adverse events and safety issues the Austrian Society of Gastroenterology and Hepatology launched this evidence based consensus on the safe use of IFX which covers the following topics: infusion reactions and immunogenicity, skin reactions, opportunistic infections (including tuberculosis), non-opportunistic infections (bacterial and viral), vaccination, neurological complications, hepatotoxicity, congestive heart failure, haematological side effects, intestinal strictures, stenosis and bowel obstruction (SSO), concomitant medication, malignancy and lymphoma, IFX in the elderly and the young, mortality, fertility, pregnancy and breast feeding. To make the vast amount of information practicable for routine application the consensus was finally condensed into a checklist for a safe use of IFX which consists of two parts: issues to be addressed prior to anti-TNF therapy and issues to be addressed during maintenance. Both parts are further divided into obligatory and facultative items.
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Affiliation(s)
- W Miehsler
- Department of Internal Medicine 3, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria.
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41
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Stein DJ, Ananthakrishnan AN, Issa M, Williams JB, Beaulieu DB, Zadvornova Y, Ward A, Johnson K, Knox JF, Skaros S, Binion DG. Impact of prior irregular infliximab dosing on performance of long-term infliximab maintenance therapy in Crohn's disease. Inflamm Bowel Dis 2010; 16:1173-9. [PMID: 19924800 DOI: 10.1002/ibd.21164] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Infliximab is efficacious in the management of moderate to severe Crohn's disease (CD). There are limited data regarding performance of infliximab in patients who require reinitiation of maintenance dosing following previous irregular exposure. METHODS This was a retrospective, observational study of CD patients treated with maintenance infliximab beyond 3 years. Maintenance infliximab infusion regimens were categorized as scheduled maintenance (SM) (maintenance infusions q < or =8 weeks after loading) or prior irregular (PI) (no loading, gap in therapy >8 weeks prior to or during maintenance therapy). We examined differences in need for medical and surgical hospitalizations as well as associated healthcare costs between the 2 groups. RESULTS In all, 104 CD patients met criteria for 3-year maintenance infliximab treatment (SM n = 64; PI n = 40). The rates of CD-related surgeries (60.9% and 55.0%, P = not significant [N.S.]) and medical hospitalizations (35.9% and 37.5%, P = N.S.) prior to infliximab initiation was similar between the 2 groups. However, the rate of medical (26.5% versus 47.5%, P = 0.035) and surgical hospitalizations (21.8% versus 48.7%, P = 0.009) were significantly lower in the SM compared to the PI group. During the third year of treatment the excess costs per patient for the PI group compared to the SM group amounted to $11,464 in spite of both cohorts being on SM therapy. CONCLUSIONS Patients who begin and continue an uninterrupted maintenance dosing regimen had a lower incidence of hospitalization and surgery than those who received an irregular or interrupted regimen prior to beginning an SM regimen.
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Affiliation(s)
- Daniel J Stein
- Medical College of Wisconsin Division of Gastroenterology, Milwaukee, Wisconsin, USA
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42
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Bousvaros A. Use of immunomodulators and biologic therapies in children with inflammatory bowel disease. Expert Rev Clin Immunol 2010; 6:659-666. [DOI: 10.1586/eci.10.46] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Best practices in multiple sclerosis: infusion reactions versus hypersensitivity associated with biologic therapies. JOURNAL OF INFUSION NURSING 2010; 33:98-111. [PMID: 20228647 DOI: 10.1097/nan.0b013e3181cfd36d] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Infusion nurses are uniquely positioned to play a vital role in the early identification and management of infusion and hypersensitivity reactions during the administration of biologic therapies. This article reviews the current evidence regarding reactions related to the administration of monoclonal antibodies, namely, natalizumab, a humanized monoclonal antibody against the cellular adhesion molecule alpha4-integrin, in patients with multiple sclerosis. In addition to differentiating between infusion and hypersensitivity reactions, the article presents general guidelines for the management of these reactions and provides case studies to better illustrate the use of appropriate interventions.
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44
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[Protocol for inducing infliximab tolerance in a patient with psoriatic spondylarthritis]. FARMACIA HOSPITALARIA 2010; 34:94-6. [PMID: 20304368 DOI: 10.1016/j.farma.2009.10.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2009] [Revised: 10/05/2009] [Accepted: 10/08/2009] [Indexed: 01/24/2023] Open
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Infliximab reintroduction is not associated to a higher rate of immune-related adverse effects in patients with inflammatory bowel disease initially treated with a three-infusion induction regimen. J Clin Gastroenterol 2010; 44:34-7. [PMID: 19417683 DOI: 10.1097/mcg.0b013e3181962dfa] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Episodic infliximab (IFX) treatment is associated with a higher risk for acute infusion reactions (AIR) and secondary loss of response (SLR), but this has not been evaluated in patients initially treated with an induction regimen with 3 IFX infusions. AIMS To evaluate whether IFX reintroduction after > or = 4 months in patients treated with a 3-infusion induction regimen is associated with a higher incidence of AIR or SLR. METHODS Incidence of immunogenic adverse effects was assessed in patients with inflammatory bowel disease who received > or = 4 consecutive IFX infusions (3 infusions at weeks 0, 2, and 6, plus > or = 1 maintenance infusion) (Continuous, n=47) and patients who were treated with a successful initial 3-infusion induction scheme and in whom IFX was then discontinued because of a complete response but reintroduced > or = 4 months later (Reintro, n=29). RESULTS AIR rate was 17% in both groups, and SLR rate was 26% in the Continuous group and 15% in the Reintro group (not significant). The lack of concomitant immunomodulators and/or pretreatment with hydrocortisone were associated with AIR development (P=0.002). CONCLUSIONS In patients who completed a 3-infusion induction regimen, IFX can be safely reintroduced even after a long time from discontinuation.
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46
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Gonzaga JE, Ananthakrishnan AN, Issa M, Beaulieu DB, Skaros S, Zadvornova Y, Johnson K, Otterson MF, Binion DG. Durability of infliximab in Crohn's disease: a single-center experience. Inflamm Bowel Dis 2009; 15:1837-43. [PMID: 19462426 DOI: 10.1002/ibd.20974] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2009] [Accepted: 03/27/2009] [Indexed: 12/13/2022]
Abstract
BACKGROUND Infliximab is effective maintenance for moderate to severe Crohn's disease (CD); however, problems with immunogenicity and decreased efficacy often complicate long-term use. Durability of infliximab maintenance therapy over multiple years has not been defined. METHODS This was a retrospective, observational study of CD patients who received maintenance infliximab for ≥1 year with the intention of ongoing maintenance. Patients were categorized into those who either discontinued treatment or continued maintenance therapy. We examined the impact of demographic, clinical characteristics, and prior episodic exposure on long-term durability of infliximab therapy and also examined the reasons for discontinuation of therapy. RESULTS A total of 153 CD patients received maintenance infliximab treatment beyond 1 year and 42 (27%) ultimately discontinued treatment. The mean duration of maintenance treatment at the time of discontinuation was 42.4 ± 19.1 months compared to a follow-up period of 49.4 ± 19.8 months in the cohort continuing therapy (P = 0.049). The main reasons for discontinuation were allergy/adverse reaction (44.2%) and decreased efficacy (38.2%). Use of concomitant immunosuppression was similar between the 2 groups (78.6% versus 83.8%, P = NS). However, the discontinued group had a higher rate of prior episodic dosing compared to CD patients who continued maintenance (28.8% versus 11.7%, P = 0.025), while there was no difference in the rate of intensified dosing (57.2% versus 50.5%, P = NS). CONCLUSIONS One-quarter of CD patients on long-term infliximab maintenance discontinued treatment. A history of prior episodic dosing was significantly associated with infliximab discontinuation, despite concomitant immunosuppression. These data emphasize the need for optimization of infliximab for successful long-term management.
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Affiliation(s)
- Jason E Gonzaga
- Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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Lichtenstein GR, Diamond RH, Wagner CL, Fasanmade AA, Olson AD, Marano CW, Johanns J, Lang Y, Sandborn WJ. Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD-subgroup analyses across four randomized trials. Aliment Pharmacol Ther 2009; 30:210-26. [PMID: 19392858 DOI: 10.1111/j.1365-2036.2009.04027.x] [Citation(s) in RCA: 99] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Benefits and risks of concomitant immunomodulators and maintenance infliximab in inflammatory bowel disease (IBD) patients have not been adequately evaluated. AIM To assess the effect of concomitant immunomodulator and infliximab maintenance therapy using data from four prospective, randomized Phase 3 trials in IBD patients. METHODS Overall, 1383 patients from ACCENT I and ACCENT II [luminal and fistulizing Crohn's disease trials] and ACT 1 and ACT 2 [ulcerative colitis trials] were analysed. Patients were treated with placebo or infliximab 5 or 10 mg/kg at weeks 0, 2 and 6 followed by every-8-week maintenance therapy. Clinical response, clinical remission, fistula response, complete fistula response, infection and infusion reaction rates; serum infliximab concentrations and immunogenicity were summarized by baseline concomitant immunomodulator subgroup (use or non-use). RESULTS Overall, almost 40% of evaluated IBD patients received concomitant immunomodulators. Efficacy, infection, and serious infection rates were generally similar in patients who received maintenance therapy with or without concomitant immunomodulators. There were no consistent differences in serum infliximab concentrations with or without immunomodulators in patients who received scheduled maintenance therapy. Concomitant immunomodulators reduced infusion reactions and immunogenicity. CONCLUSION Concomitant immunomodulators did not improve efficacy or pharmacokinetics in IBD patients who received maintenance infliximab.
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Affiliation(s)
- G R Lichtenstein
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
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Ruemmele FM, Lachaux A, Cézard JP, Morali A, Maurage C, Giniès JL, Viola S, Goulet O, Lamireau T, Scaillon M, Breton A, Sarles J. Efficacy of infliximab in pediatric Crohn's disease: a randomized multicenter open-label trial comparing scheduled to on demand maintenance therapy. Inflamm Bowel Dis 2009; 15:388-94. [PMID: 19023899 DOI: 10.1002/ibd.20788] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Infliximab (IFX) is efficacious in inducing remission in severe forms of pediatric Crohn's disease (CD). Adult studies indicate that IFX is also safe and well tolerated as maintenance therapy. The present study aimed to evaluate in a prospective manner the efficacy and safety of IFX as maintenance therapy of severe pediatric CD comparing scheduled and "on demand" treatment strategies. METHODS Forty children with CD (nonpenetrating, nonstricturing as well as penetrating forms, mean age: 13.9 +/- 2.2 years) with a severe flare-up (Harvey-Bradshaw Index [HBI] > or =5, erythrocyte sedimentation rate [ESR] >20 mm/h) despite well-conducted immunomodulator therapy (n = 36 azathioprine, n = 1 mercaptopurine, n = 3 methotrexate) combined with steroids were included in this randomized, multicenter, open-label study. Three IFX infusions (5 mg/kg) were administered at week (W)0/W2/W6. At W10, clinical remission (HBI <5) and steroid withdrawal were analyzed and IFX responders were randomized to maintenance therapy over 1 year: group A, scheduled every 2 months; group B, "on demand" on relapse. RESULTS In all, 34/40 children came into remission during IFX induction therapy (HBI: 6.7 +/- 2.5 (WO) vs. 1.1 +/- 1.5 (W10); P < 0.001). At the end of phase 2, 15/18 (83%) patients were in remission in group A compared to 8/13 (61%) children in group B (P < 0.01), with a mean HBI of 0.5 versus 3.2 points (group A versus B, P = 0.011). In group A, 3/13 (23.1%) children experienced a relapse compared to 11/12 (92%) children in group B. No severe adverse event occurred during this trial. CONCLUSIONS IFX is well tolerated and safe as maintenance therapy for pediatric CD, with a clear advantage when used on a scheduled 2-month basis compared to an "on demand" basis.
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Affiliation(s)
- Frank M Ruemmele
- AP-HP, Hôpital Necker-Enfants Malades, Department of Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition, Paris, France.
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Vermeire S, Van Assche G, Rutgeerts P. Serum sickness, encephalitis and other complications of anti-cytokine therapy. Best Pract Res Clin Gastroenterol 2009; 23:101-12. [PMID: 19258190 DOI: 10.1016/j.bpg.2008.12.005] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The introduction of biological therapies has greatly advanced the therapeutic armamentarium of the inflammatory bowel diseases Crohn's disease and ulcerative colitis. At present, three anti-tumour necrosis factor (TNF) agents (infliximab, adalimumab and certolizumab pegol) and one anti-adhesion cytokine (natalizumab) have been approved and have shown efficacy in luminal and/or fistulizing Crohn's disease and/or in ulcerative colitis. Although the overall benefit/risk ratio for the anti-TNF agents is positive, of particular concern has been the problem of immunogenicity ascribed to the formation of antibodies to these molecules. Antibody formation is associated with allergic reactions and loss of response through decreased trough serum concentrations. Ways to reduce antibody formation include maintenance therapy, the use of concomitant immunomodulators and pre-treatment with corticosteroids. Other safety concerns include the occurrence of opportunistic infections, skin manifestations, and the rare but often lethal hepatosplenic T-cell lymphoma. The alpha-4 integrin natalizumab has been associated with three cases of progressive multifocal leucoencephalopathy and was the reason for which the drug was not approved in Europe, and is available only through a specialised programme in the US. We discuss the safety aspects of the biological agents in this chapter and, where available, give ways to prevent and/or treat them.
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Pérez-Zafrilla B, Angel Descalzo M, Carmona L. [Adverse Reactions Related to the Administration of TNF Inhibitors. Analysis of a Registry of Biologic Therapy]. ACTA ACUST UNITED AC 2008; 4:90-5. [PMID: 21794507 DOI: 10.1016/s1699-258x(08)71810-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2007] [Accepted: 02/07/2008] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To estimate the frequency of administration related reactions (ARR), the risk window from the starting date, and finally if there are any differences between infliximab, etanercept and adalimumab. PATIENTS AND METHOD BIOBADASER is an adverse events registry established in 2001 for active long-term follow-up of safety of biological therapies in rheumatic patients. Data from patients, diagnosis, treatment, and adverse events are recorded. RESULTS Four-hundred ninety six relevant ARR were registered, 19.6% (496/2531) of all the adverse events communicated and 6.3% (496/2531) of all the patients registered. The incidence rate per 1000 patients-year with infliximab is 28 cases (95% CI, 25-31), with etanercept 0.2 (95% CI, 0.1-0.4) and with adalimumab 0.2 (95% CI, 0.07-0.7). Treatment was interrupted in more than 50% of all the ARR and 5% of all patients were hospitalized. More than 20% ARR happened after 15 months of treatment; in addition 2 appeared after 5 years of treatment. In delayed reactions the symptoms that most frequently were recorded were rash, fever, malaise, and myalgia. CONCLUSIONS ARR can appear in any moment of the treatment; they are among the most frequent causes of treatment interruption. Although with less frequency, ARR are also associated with etanercept and adalimumab with symptoms that cannot be identified as such.
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