Biosimilars Associated With Clinically Equivalent Treatment Effects vs Reference Biologics in RA

Safety and immunogenicity profiles of biosimilars and reference biologics were similar.

Biosimilars of adalimumab, infliximab, and etanercept were found to be clinically equivalent in treatment effects compared with their reference biologics in patients with rheumatoid arthritis (RA), according to research results published in JAMA Network Open.

Tumor necrosis factor (TNF)-α inhibitors, such as infliximab, adalimumab, and etanercept, are used in the long-term treatment of RA.

A systematic review and meta-analysis was conducted to compare biosimilars with their reference drugs in RA.

Researchers conducted a comprehensive literature search for randomized controlled trials among individuals with RA, with interventions using biosimilars of adalimumab, etanercept, or infliximab, as well as their reference biologics.

Data were extracted from MEDLINE, Emboss, Cochrane Central Register of Controlled Trials, and LILACS until September 2021.

Treatment success at 6 months, specified by the American College of Rheumatology 20% response criteria (ACR20), which is a minimum of 20% improvement across set measures of RA value indices, was the primary study endpoint. Patient disability at 6 months follow-up, measured by the Health Assessment Questionnaire Disability Index (HAQ-DI), was the prespecified primary outcome. The ACR 50% and ACR 70% response criteria were secondary efficacy outcomes.

The findings support the rational use of these biosimilars for RA treatment.

A total of 25 trials (n=10,642) were included in the final analysis, with all patients with moderate to severe RA and a history of methotrexate use. Biosimilars of adalimumab were most highly investigated (11 trials), with etanercept and infliximab having 7 trials each.

Patients receiving biosimilars vs reference biologics experienced a similar ACR20 response at 6 months (79% and 78%, respectively). In addition, ACR50 and ACR70 responses of biosimilars and their reference biologics were also consistent with the primary outcome.

Bayesian random-effects standard mean deviation (-0.04; 95% CrI, -0.11 to 0.02) of HAQ-DI after 6 months of treatment found responses to be within the prespecified margins of equivalence (-0.22 to 0.22) between biosimilars and their reference biologics.

Of note, although rates of adverse events were identical in biosimilars, lower rates of treatment-emergent adverse events, injection site reactions, and the formation of antidrug antibodies were seen in patients who received biosimilars compared with reference biologics (35.9% vs 39.6%, 6.2% vs 19.9%, 30% vs 33.5%, respectively).

One of the limitations included the lack of generalizability, as the researchers did not assess reference biologics currently available in the RA market.

The study authors concluded, “This systematic review and meta-analysis found that there was compelling evidence of equivalence between adalimumab, infliximab, and etanercept biosimilars and their originators, based on ACR20 (a clinician-assessed outcome) and HAQ-DI (a patient-reported outcome). The findings support the rational use of these biosimilars for RA treatment.”

References:

Ascef BO, Almeida MO, Medeiros-Ribeiro AC, Oliveira de Andrade DC, Oliveira Junior HA, de Soárez PC. Therapeutic equivalence of biosimilar and reference biologic drugs in rheumatoid arthritis: a systematic review and meta-analysisJAMA Netw Open. 2023;6(5):e2315872. doi:10.1001/jamanetworkopen.2023.15872