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

Strand V1, Gonçalves J2, Hickling TP3, Jones HE4, Marshall L4, Isaacs JD5. BioDrugs. 2019 Nov 13. doi: 10.1007/s40259-019-00394-x. [Epub ahead of print]


Author information

Division of Immunology/Rheumatology, Stanford University School of Medicine, 306 Ramona Road, Portola Valley, Palo Alto, CA, 94028, USA. vibekestrand@me.com.

iMed-Research Institute for Medicines, Faculdade de Farmácia da, Universidade de Lisboa, Lisbon, Portugal.

Biomedicine Design, Pfizer, Andover, MA, USA.

Inflammation and Immunology, Pfizer, Collegeville, PA, USA.

Institute of Cellular Medicine, Newcastle University and Musculoskeletal Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.


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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