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Meta-Analysis
. 2017 Aug;31(4):299-316.
doi: 10.1007/s40259-017-0231-8.

Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

Vibeke Strand  1 , Alejandro Balsa  2 , Jamal Al-Saleh  3 , Leonor Barile-Fabris  4 , Takahiko Horiuchi  5 , Tsutomu Takeuchi  6 , Sadiq Lula  7 , Charles Hawes  8 , Blerina Kola  8 , Lisa Marshall  9
Affiliations
Meta-Analysis

Immunogenicity of Biologics in Chronic Inflammatory Diseases: A Systematic Review

Vibeke Strand et al. BioDrugs. 2017 Aug.

Abstract

Objectives: A systematic review was conducted to explore the immunogenicity of biologic agents across inflammatory diseases and its potential impact on efficacy/safety.

Methods: Literature 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.

Results: Of >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.

Conclusions: Based 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.

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Conflict of interest statement

Funding

The systematic literature review to support this manuscript was sponsored by Pfizer.

Conflict of interest

Vibeke Strand has received consulting fees or honoraria for AbbVie, Alder, Amgen Corporation, Anthera, Asana, AstraZeneca, aTyr, Bayer, BiogenIdec, BMS, Boehringer Ingelheim, Carbylan, Celgene, Celltrion, CORRONA, Crescendo/Myriad Genetics, EMD Serono, Eupraxia, Genentech/Roche, GlaxoSmithKline, Horizon, Iroko, Janssen, Jazz Pharmaceuticals, Kezar, Kypha, Lilly, Merck, Novartis, Pfizer, Protagen, Regeneron, Samsung, Samumed, Sandoz, Sanofi, SKK, UCB, and XTL. Alejandro Balsa has received grants from AbbVie and Pfizer and consulting fees or honoraria from AbbVie, BMS, Janssen, MSD, Novartis, Pfizer, Roche, and UCB. Jamal Al-Saleh has received fees from Pfizer for a rheumatoid arthritis registry. Leonor Barile-Fabris and Takahiko Horiuchi reported no conflicts of interest. Tsutomu Takeuchi has received grants from AbbVie GK, Asahikasei Pharma Corp, Astellas Pharma, AYUMI Pharmaceutical Corporation, Bristol-Myers K.K., Chugai Pharmaceutical Co, Daiichi Sankyo, Eisai Co, Ltd, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Pfizer Japan Inc, Sanofi Aventis K.K., Santen Pharmaceutical Co, Ltd, SymBio Pharmaceuticals Ltd, Taisho Toyama Pharmaceutical Co, Takeda Pharmaceutical Company, and Teijin Pharma Limited; consultant fees or honoraria from AbbVie GK, Asahi Kasei Medical Co, Ltd, Astellas Pharma, AstraZeneca K.K., Bristol-Myers K.K., Daiichi Sankyo Co, Ltd, Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., Merck Serono Co, Ltd, Nipponkayaku Co Ltd, Novartis Pharma K.K., Mitsubishi Tanabe Pharma Corporation, and Takeda Pharmaceutical Co, Ltd; and speaking fees from AbbVie GK, Astella Pharma, Bristol-Myers Squibb K.K., Celtrion, Chugai Pharmaceutical Co, Diaichi Sankyo Co, Ltd, Eisai Co, Ltd, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Corporation, Nipponkayaku Co Ltd, Pfizer Japan Inc, and Takeda Pharmaceutical Company. During the development of the SLR and manuscript, Sadiq Lula was an employee of Envision Pharma Group, who were paid consultants to Pfizer in connection with the development of the systematic literature review report that forms the basis of this manuscript. He was not compensated for his role in the development of this manuscript. Charles Hawes, Blerina Kola, and Lisa Marshall are full-time employees and shareholders of Pfizer.

Figures

Fig. 1
Fig. 1
Flow of publications/studies through the search and screening process
Fig. 2
Fig. 2
Immunogenic portions of molecular structures of biologic/biosimilar agents. IgG immunoglobulin G, IL interleukin, mAb monoclonal antibody, PEG polyethylene glycol, TNFi tumor necrosis factor-α inhibitor
See this image and copyright information in PMC

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