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TNFi Switching Is Safe, Effective for Rheumatoid Arthritis, Study Suggests


Single switching between approved biologics and biosimilars of tumor necrosis factor inhibitors (TNFis) were found to be safe and effective for rheumatoid arthritis.

The practice of single switching between approved biologics and biosimilars of tumor necrosis factor inhibitors (TNFis) is effective and safe for rheumatoid arthritis, according to Scientific Reports.

Researchers aimed to evaluate the impact of switching on the treatment of rheumatoid arthritis through a network of evidence of head to head comparisons of switching and nonswitching arms of TNFi biologics and biosimilars.

A systematic review and network meta-analysis were undertaken to compare switching and nonswitching groups of treatments.

The use of TNFi biosimilars for patients using disease-modifying antirheumatic drugs has been the standard of care for rheumatoid arthritis in areas around the globe where biosimilars are accessible. In circumstances where a patient will have their treatment exchanged or replaced by another treatment, the decision about switching should be based on the top level of evidence available.

First, pooled risk relative (RR) or standardized mean differences (SMD) with 95% credible intervals (95% CrIs) were collected. A total of 17 randomized trials with a switching phase involving 6,562 patients were included.

Results demonstrated that just 1 switch from biologics to biosimilars compared to continuing biologics had comparable effects for primary and co-primary outcomes, the American College of Rheumatology criteria with 20% response (ACR20; 7 trials; n = 1,926 patients; RR, 0.98; 95% CrIs, 0.93-1.03) and the Health Assessment Questionnaire–Disability Index (HAQ-DI; 5 trials; n = 1,609 patients; SMD, –0.07; 95% CrIs, –0.23 to 0.1), and within the equivalence margins of ACR20 (RR, 0.94, 1.06) and HAQ-DI (SMD, –0.22 to 0.22). The possibility of treatment-emergent adverse events, discontinuation, and positive anti-drug antibodies were comparable after switching.

Safety results weren’t precise, and the follow-up period might not be adequate to review long-term effects, especially malignancies.

Then, in terms of safety, the evidence displayed that the risk for both outcomes was similar within and between switching and nonswitching arms. The 95% CrIs for the risk for serious treatment emergent adverse events (TEAEs), hypersensitivity, infusion-related reactions, malignancies, and serious infections crossed the null effect but weren’t precise (small number of events and high heterogeneity between trials). The researchers weren’t able to perform network metal analysis (NMA) for ISRs, active tuberculosis, and mortality because of rare event rates (n < 30).

The clinical response or functional capacity of patients following switching was equal within and between switching and nonswitching groups, and all comparisons met previously stated margins of equivalence. Additionally, there is evidence of a similar risk of experiencing TEAE or stopping study rates (i.e., comparable safety and tolerability were seen after switching). Since the rare rates of some adverse events, the researchers aren’t sure about the effects of switching in these cases. The immune response was comparable for patients in the switching and nonswitching treatment arms.

Even though the researchers extended the finding that these trials were at high risk of bias, new studies should try to incorporate vital aspects of quality and reporting when evaluating the impact of switching between treatments.

Importantly, their evidence does not focus on the issue of switching from a biosimilar to another biosimilar of the same reference biologic drugs or multiple switches. These questions persist and should be the concern of future research.

To the best of the researchers’ knowledge, this study is the most comprehensive systematic review and NMA within a Bayesian framework to review the impact of switching between biosimilars of adalimumab, etanercept, and infliximab and its reference biologics drugs on rheumatoid arthritis treatment.

Some limitations were present in this study. First, multiple comparisons such as arm switching (biosimilar to reference product) comprised of only 1 or a few studies, constricting the confidence of estimates. Secondly, special attention should be paid to the interpretation of some safety and immunogenicity outcomes, that indicated the null effect between switching and nonswitching arms.

Even though safety results were imprecise, and the follow-up period may not be sufficiently long enough, especially regarding malignancies, “these findings support the rational practice of switching reference biologics and biosimilar drugs of adalimumab, etanercept, and infliximab for patients with rheumatoid arthritis,” concluded the study authors.


de Oliveira Ascef B, Almeida MO, de Medeiros-Ribeiro AC, de Oliveira Andrade DC, de Oliveira Junior HA, de Soárez PC. Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis. Sci Rep. Published online August 22, 2023. doi:10.1038/s41598-023-40222-5

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