Switching Between TNF Biologics, Biosimilars Deemed Safe in RA

Single switching between approved tumor necrosis factor inhibitor (TNF) biologics and biosimilars was demonstrated to be safe and effective in patients with rheumatoid arthritis (RA), according to a study published in Scientific Reports.¹

Bruna de Oliveira Ascef, PhD, PharmD

Credit: ResearchGate

Biosimilars, a cost-saving alternative to the bio-originator, are complex molecules designed to be highly similar regarding safety, efficacy, and quality to the biologic reference product. In particular, TNF biosimilars for patients receiving biologic disease-modifying antirheumatic drugs (bDMARDs) have been a staple for patients with RA when available. The decision to switch from a biologic to a biosimilar should be made based on available evidence.²

“The key question about biosimilars is whether switching from the reference biologic to a biosimilar or within multiple switching scenarios would affect the response to the treatment,” wrote lead investigator Bruna de Oliveira Ascef, PhD, PharmD, associated with the Department of Preventative Medicine, University of São Paulo, Brazil, and colleagues. “In clinical practice, concerns arose with switching which possibly could lead to increased immune reactions, loss of efficacy, and/or more risk of safety issues. There is no scientific rationale to support or refute these concerns.”

To determine the efficacy and safety of switching between adalimumab, infliximab, and etanercept biologics compared with their respective biosimilars, a systemic review and network meta-analysis evaluated both switching and non-switching cohorts. Eligible patients had a diagnosis of RA and eligible studies were randomized controlled trials (RCTs) or quasi-RCTs which assessed the impact of switching between the reference product and a biosimilar. The time point of interest for all outcomes was 6 months post-switch. Pooled risk relative (RR) or standardized mean differences (SMD) with 95% credible intervals (CrIs) were collected.

A total of 17 randomized trials with a switching phase comprised of 6562 patients were included in the analysis. Of these trials, 3 included a second switching phase. A single switch from biologic treatment to biosimilars demonstrated comparable effects for both primary (treatment efficacy at 6 months post-switch) and co-primary (the Health Assessment Questionnaire—Disability Index [HAQ-DI]) outcomes.

In 7 trials (n = 1926 patients), the American College of Rheumatology 20% improvement response criteria (ACR20) showed comparable efficacy (RR .98, 95% CrIs .93 to 1.03). Similar results were demonstrated in 5 trials (n = 1609 patients) evaluating HAQ-DI (SMD − .07, 95% CrIs − .23 to .1). The ACR20 and HAQ-DI were also within the equivalence margins (RR .94, 1.06; and SMD − .22, .22, respectively).

Discontinuation, treatment-emergent adverse events (TEAEs), and positive anti-drug antibodies were similar after switching between drugs. Serious TEAEs and hypersensitivity crossed the null effect although they were imprecise due to the small number of events and high heterogeneity between trials. The risk for both outcomes was comparable within and between the switching and non-switching cohorts. A higher probability of publication bias was indicated due to the suspected asymmetry in the comparison-adjusted funnel plots for ACR20, ACR50, ACR70, and serious TEAEs.

Certain outcomes, such as serious infections, reported minimal data. Additionally, investigators noted by including trials comparing 3 different molecules, they were unable to detect any differences inherent to each drug. As the study only evaluated the impact of switching after 6 months, they were also unable to assess the impact of multiple switches or long-term effects.

“These findings support the rational practice of switching reference biologics and biosimilar drugs of adalimumab, etanercept, and infliximab for patients with rheumatoid arthritis,” investigators concluded.

References

1. ^{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. 2023;13(1):13699. Published 2023 Aug 22. doi:10.1038/s41598-023-40222-5}
2. ^{Kay, J. et al. Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases. Ann. Rheum. Dis. 77, 165–174. https://doi.org/10.1136/annrheumdis-2017-211937 (2018)}