Etanercept biosimilar(Mochida Pharmaceutical Co., Ltd.)

We aimed to assess the relative efficacy and safety of etanercept biosimilars and etanercept originators in patients with active rheumatoid arthritis (RA) who showed an inadequate response to methotrexate (MTX).

We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of etanercept biosimilars vs. etanercept originators in patients with active RA despite treatment with MTX.

Three RCTs involving 1,200 patients, including 4 types of biologics, were included. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that LBEC0101 had a high probability of being the better treatment in terms of the American College of Rheumatology 20 (ACR20) response rate (SUCRA = 0.744), followed by HD203 (SUCRA = 0.457), SB4 (SUCRA = 0.446), and etanercept (SUCRA = 0.352), although no difference in the ACR20 response rate between the biosimilars and etanercept groups was found. Although not statistically significant, there was a difference in the ranking probability of safety based on serious adverse events (SAEs) among interventions. Ranking probability based on SUCRA values indicated that LBEC0101 had the highest probability of being the safest treatment (SUCRA = 0.638), followed by SB4 (SUCRA = 0.495) and HD203 (SUCRA = 0.475), while etanercept had the lowest probability of being the safest treatment (SUCRA = 0.393).

No significant difference was found between etanercept biosimilars and etanercept originators in patients with active RA despite treatment with MTX in terms of the ACR20 response rate and SAEs.

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.