P-101 Incidence of Anti-drug Antibodies in Crohnʼs Disease Patients During 5 Years of Certolizumab Pegol Therapy

Sandborn, William J.; Dubinsky, Marla; Kosutic, Gordana; Parker, Adwoa; Spearman, Marshall; Hasan, Iram; Coarse, Jason; Ptak, Theodore; Younes, Ziad; Shafran, Ira; Lee, Scott; Afzali, Anita; Khanna, Reena; Feagan, Brian G.

doi:10.1097/01.mib.0000480206.37277.e8

Cited by 4 publications

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“…An integrated analysis of 5-year follow-up of the PRECiSE trial showed a lower range of mean drug serum concentrations in ADA-positive versus ADA-negative patients (0.88-15.25 vs 8.33-29.89 µg/mL) and no influence of ADA formation on adverse events [40].…”

Section: Serum Drug Concentrationsmentioning

confidence: 96%

Anti-Drug Antibody Formation Against Biologic Agents in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Bots

Parker²,

Brandse

et al. 2021

BioDrugs

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Background and aims Immunogenicity with formation of anti-drug antibodies (ADA) to biologics is an important reason for treatment failure in inflammatory bowel disease (IBD). Our aim was to assess the rate of ADA, the effect of combination therapy with immunomodulators on ADA and the influence of ADA on efficacy and safety of biologics for IBD treatment. Methods MEDLINE, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to April 2020 for trials of biologics that assessed immunogenicity. The overall certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). The primary outcome was rate of ADA. Secondary outcomes included efficacy and safety outcomes among patients with detectable versus undetectable ADA. For dichotomous outcomes, pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated. Results Data from 68 studies were analyzed and 33 studies (5850 patients) were included in the meta-analysis. Pooled ADA rates for biologic monotherapy were 28.0% for infliximab, 7.5% for adalimumab, 3.8% for golimumab, 10.9% for certolizumab, 6.2% for ustekinumab and 16.0% for natalizumab. Pooled ADA rates were 8.4% for vedolizumab and 5.0% for etrolizumab for combo-and monotherapy combined. In all biologics, ADA rates were underestimated by use of drug-sensitive ADA assays and higher dose and/or frequency. ADA rate was significantly reduced in patients treated with combination therapy for infliximab (RR 0.52; 95% CI 0.44-0.62), adalimumab (RR 0.31; 95% CI 0.14-0.69), golimumab (RR 0.29; 95% CI 0.10-0.83), certolizumab pegol (RR 0.30; 95% CI 0.14-0.67) and natalizumab (RR 0.20; 95% CI 0.11-0. 39). ADA to infliximab were associated with lower clinical response rates (RR 0.75; 95% CI 0.61-0.91) and higher rates of infusion reactions (RR 2.36; 95% CI 1.85-3.01). Conclusions Differences in analytical methods to detect ADA hamper comparison of true ADA rates across biologics in IBD. Use of combination therapy with immunomodulators appeared to reduce ADA positivity for most biologics. For infliximab, ADA were associated with reduced drug efficacy and increased adverse events.

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Section: Serum Drug Concentrationsmentioning

confidence: 96%

Anti-Drug Antibody Formation Against Biologic Agents in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Bots

Parker²,

Brandse

et al. 2021

BioDrugs

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Certolizumab pegol for maintenance of medically induced remission in Crohn’s disease

Okabayashi

Yamazaki

Yamamoto

et al. 2022

Cochrane Database of Systematic Reviews

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Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

et al. 2017

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ObjectivesA systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety.MethodsLiterature searches were conducted through November 2016 to identify controlled and observational studies of biologics/biosimilars administered for treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), psoriasis (Ps), Crohn’s disease, and ulcerative colitis.ResultsOf >21,000 screened publications, 443 were included. Anti-drug antibody (ADAb) rates varied widely among biologics across diseases (and are not directly comparable because of immunoassay heterogeneity); the highest overall rates were reported with infliximab (0–83%), adalimumab (0–54%), and infliximab biosimilar CT-P13 (21–52%), and the lowest with secukinumab (0–1%), ustekinumab (1–11%), etanercept (0–13%), and golimumab (0–19%). Most ADAbs were neutralizing, except those to abatacept and etanercept. ADAb+ versus ADAb− patients had lower rates of clinical response to adalimumab (RA, PsA, JIA, AS, Ps), golimumab (RA), infliximab (RA, PsA, AS, Ps), rituximab (RA), ustekinumab (Ps), and CT-P13 (RA, AS). Higher rates of infusion-related reactions were reported in infliximab- and CT-P13-treated ADAb+ patients. Background immunosuppressives/anti-proliferatives reduced biologic immunogenicity across diseases.ConclusionsBased on reviewed reports, biologic/biosimilar immunogenicity differs among agents, with the highest rates observed with infliximab and adalimumab. As ADAb formation in biologic-/biosimilar-treated patients may increase the risk of lost response, the immunogenicity of these agents is an important (albeit not the only) consideration in the treatment decision-making process.Electronic supplementary materialThe online version of this article (doi:10.1007/s40259-017-0231-8) contains supplementary material, which is available to authorized users.

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P-101 Incidence of Anti-drug Antibodies in Crohnʼs Disease Patients During 5 Years of Certolizumab Pegol Therapy

Cited by 4 publications

References 0 publications

Anti-Drug Antibody Formation Against Biologic Agents in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Anti-Drug Antibody Formation Against Biologic Agents in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Certolizumab pegol for maintenance of medically induced remission in Crohn’s disease

Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

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