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Review
. 2020 Feb;34(1):27-37.
doi: 10.1007/s40259-019-00394-x.

Immunogenicity of Biosimilars for Rheumatic Diseases, Plaque Psoriasis, and Inflammatory Bowel Disease: A Review from Clinical Trials and Regulatory Documents

Vibeke Strand  1 , Joao Gonçalves  2 , Timothy P Hickling  3 , Heather E Jones  4 , Lisa Marshall  4 , John D Isaacs  5
Affiliations
Review

Immunogenicity of Biosimilars for Rheumatic Diseases, Plaque Psoriasis, and Inflammatory Bowel Disease: A Review from Clinical Trials and Regulatory Documents

Vibeke Strand et al. BioDrugs. 2020 Feb.

Erratum in

Abstract

The goal of this narrative review was to summarize immunogenicity data of biosimilars or biosimilar candidates for rheumatic diseases, plaque psoriasis, or inflammatory bowel disease (IBD), available in peer-reviewed publications or regulatory documents. PubMed records and regulatory documents were searched for immunogenicity data of TNFα or CD20 inhibitor biosimilars or biosimilar candidates. Data collected included the proportion of patients positive for anti-drug antibodies (ADAbs), proportion with neutralizing antibodies (nAbs) among ADAb-positive patients, ADAb/nAb assay characteristics, cross-reactivity, and the effects of ADAbs on pharmacokinetics, pharmacodynamics, efficacy, and safety. We identified eight biosimilars or biosimilar candidates for adalimumab (BI 695501, SB5, ABP 501, GP2017, PF-06410293, MSB-11022, FKB-327, ZRC-3197) four for etanercept (SB4, GP2015, CHS-0214, LBEC0101), and three each for infliximab (SB2, CT-P13, GP1111) and rituximab (CT-P10, GP2013, PF-05280586) with immunogenicity data. Randomized, head-to-head trials with reference products varied in design and methodology of ADAb/nAb detection. The lowest proportions of ADAb-positive (0-13%) and nAb-positive patients (0-3%) were observed in the trials of etanercept and its biosimilars, and the highest with adalimumab, infliximab, and their biosimilars (ADAbs: ≤ 64%; nAbs: ≤ 100%). The most common method of ADAb detection was electrochemiluminescence, and ADAb positivity was associated with nominally inferior efficacy and safety. Overall, there were no significant immunogenicity differences between biosimilars and reference products. However, there are many discrepancies in assessing and reporting clinical immunogenicity. In conclusion, immunogenicity data of biosimilars or biosimilar candidates for TNFα or CD20 inhibitors were collected in trials that varied in design and procedures for ADAb/nAb detection. In general, immunogenicity parameters of biosimilars are similar to those of their reference products.

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Conflict of interest statement

Professor Isaacs and work in the Isaacs’ laboratory are supported in part by NIHR Newcastle Biomedical Research Centre, based at Newcastle Hospitals NHS Foundation Trust and Newcastle University and by the Research into Inflammatory Arthritis Centre Versus Arthritis. V. Strand has received consulting fees or honoraria from AbbVie, Amgen, Asana, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Celltrion, EMD Serono, Genentech/Roche, GSK, Janssen, Kezar, Kypha, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Sanofi, and UCB. J. Gonçalves has received speaker fees from Amgen, Biogen, Celltrion, Libbs, Novartis, Pfizer, Samsung Bioepis, and Sandoz. J. D. Isaacs has received speaker or consulting fees from AbbVie, Biogen, BMS, Celltrion, Eli Lilly, Gilead, Janssen, Merck, Merck Serono, Pfizer, and Roche. T. P. Hickling is an employee of Pfizer and may own company stock. H. E. Jones and L. Marshall were employees of Pfizer during the development of the manuscript and may own company stock.

Figures

Fig. 1
Fig. 1
Incidence of ADAbs (in treatment groups overall) and nAbs (in ADAb-positive individuals) in healthy volunteers, by study week. a, b Incidences of ADAbs and nAbs, respectively. ADAbs anti-drug antibodies, nAbs neutralizing antibodies
Fig. 2
Fig. 2
Incidence of ADAbs (in treatment groups overall) and nAbs (in ADAb-positive individuals) in patients with rheumatic diseases, plaque psoriasis, or inflammatory bowel disease, by study week* [results of switching treatments are excluded]. a, b Indicate incidences of ADAbs and nAbs, respectively. ADAbs anti-drug antibodies, nAbs neutralizing antibodies
Fig. 3
Fig. 3
The effect of ADAbs on serum concentration of adalimumab and its biosimilar ABP 501 after a single dose in healthy volunteers. Reproduced from Kaur P et al, Ann Rheum Dis. 2017;76:526–533 [21], with permission, under the license CC BY-NC 4.0 (https://creativecommons.org/licenses/by-nc/4.0/). Lines represent individual pharmacokinetics profiles of adalimumab (US or EU) and ABP 501 in ADAb-negative (blue) and ADAb-positive patients (orange). Bold lines represent mean values. ADAbs anti-drug antibodies
See this image and copyright information in PMC

References

    1. Dörner T, Strand V, Castaneda-Hernandez G, Ferraccioli G, Isaacs JD, Kvien TK, et al. The role of biosimilars in the treatment of rheumatic diseases. Ann Rheum Dis. 2013;72(3):322–328. - PubMed
    1. Dörner T, Strand V, Cornes P, Goncalves J, Gulacsi L, Kay J, et al. The changing landscape of biosimilars in rheumatology. Ann Rheum Dis. 2016;75(6):974–982. - PMC - PubMed
    1. Strand V, Kimberly R, Isaacs JD. Biologic therapies in rheumatology: lessons learned, future directions. Nat Rev Drug Discov. 2007;6(1):75–92. - PubMed
    1. Ellis AG, Flohr C, Drucker AM. Network meta-analyses of systemic treatments for psoriasis: a critical appraisal. Br J Dermatol. 2017;180(2):282–288. - PubMed
    1. Rawla P, Sunkara T, Raj JP. Role of biologics and biosimilars in inflammatory bowel disease: current trends and future perspectives. J Inflamm Res. 2018;11:215–226. - PMC - PubMed

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