Switch from TNF Inhibitors to Biosimilars Provides Consistent Rheumatoid Arthritis Outcomes

Bruna de Oliveira Ascef, PhD

Credit: ResearchGate

Single switching from tumor necrosis factor (TNF) inhibitor biologics to reference biosimilars are generally efficacious and safe in the treatment of patients with rheumatoid arthritis, according to new research.

A new study from a team of Brazil investigators showed patients who were switched from the common biologic drug class to a reference biosimilar reported similar rates of American College of Rheumatology 20% response criteria (ACR20) to patients who maintained biologics for their rheumatoid arthritis. The systematic review, which investigators believe to be the most comprehensive of its kind with regard to available TNF inhibitor biosimilars, provide evidence to clinical framework that introduces more cost-effective biosimilar alternatives to standard-care adalimumab, etanercept, and infliximab.

Investigators led by Bruna de Oliveira Ascef, PhD, of the department of preventive medicine at the University of Sao Paulo, sought to analyze the impact of switching treatment for rheumatoid arthritis through a review of head-to-head comparisons of switching and non-switching arms of TNF inhibitor biologics and biosimilars.

“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,” they wrote. “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.”

The team conducted their systematic review and network meta-analysis using data from comparator trials involving adalimumab, etanercept, and infliximab in the treatment of patients with rheumatoid arthritis. Their primary efficacy endpoint was treatment success at 6 monhs post-first switch from biologic to biosimilar, per ACR20. The co-primary outcome included results on the Health Assessment Questionnaire – Disability Index (HAQ-DI) 6 months post-first switch. Secondary outcomes included safety and immunogenicity outcomes, primarily as they related to treatment-emergency adverse events (TEAEs).

The final analysis included data from 6562 patients across 17 relevant randomized trials that included a switching phase. Median patient age was 53.0 years old; 80% of participants were female, and median duration of rheumatoid arthritis was 7 years.

Ascef and colleagues reported that, per 7 relevant trials, a single switch from any of the 3 TNF inhibitors to biosimilars was associated comparable efficacy per ACR20 (relative risk [RR], 0.98; 95% CI, 0.93 – 1.03). Per 5 relevant trials, the single switch to biosimilars was additionally associated with comparable HAQ-DI outcomes (standardized mean difference, -0.07; 95% CI, -0.23 to 0.1).

The team additionally observed comparable risks of TEAEs, discontinuation and positive anti-drug antibodies between switched and continued treatment arms—indicating consistent safety and immunogenicity. However, “imprecise” safety results regarding insufficient follow-up analyses into greater risks like malignancies were reported.

“The robust findings from our network meta-analysis add to the other systematic reviews providing together enough evidence to support switching between reference biologics and biosimilars of TNF inhibitorss in patients with rheumatoid arthritis,” investigators wrote. “This conclusion is in line with publications of the main medical societies of rheumatoid arthritis supporting the single switch from a reference biologic to an approved biosimilar in clinical practice.”

The investigators concluded their findings provide “compelling evidence” that switching from biologic to biosimilars in patients with rheumatoid arthritis is not disruptive to treatment efficacy and safety outcomes.

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

Reference

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