The biosimilars were equivalent with the biologic regarding both ACR20 response achievement and change of Health Assessment Questionnaire-Disability Index (HAQ-DI) scores at month 6.
Results of a systematic review and meta-analysis showed adalimumab, infliximab, and etanercept biosimilars were clinically equivalent regarding treatment efficacy and disease management when compared with their reference biologics in patients with rheumatoid arthritis (RA), according to a study published in JAMA Network Open.1
Although biosimilars are potentially lower-cost versions of biologics that may be able to improve access to therapy, there a lack of adequate systematic reviews proving equivalence between drugs for the treatment of RA. Further, international guideline recommendations have relied mainly on single trials or expert consensus.2
“Previous systematic reviewsattempted to compile evidence on similar efficacy and safety between biosimilars and reference products for RA,” wrote Bruna de Oliveira Ascef, MD, PhD, Departamento de Medicina Preventiva, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil, and colleagues. “Nonetheless, most of these reviewsprovided only qualitative summaries, which are insufficient for decision-making. The few reviewsthat attempted quantitative analyses did not use appropriate equivalence testing methods, resulting in imprecise conclusions.”
Investigators searched PubMed, Cochrane Central Register of Controlled Trials, Embase, and LILACS databases through September 2021 to include head-to-head randomized clinical trials (RCTs) of biosimilars of the tumor necrosis factor inhibitors (TNF) adalimumab, etanercept, and infliximab and their reference drugs.
Particular domains were assessed for bias risk in equivalence and noninferiority trials. The prespecified primary efficacy endpoint was treatment success at month 6 using the American College of Rheumatology (ACR) criteria, with at least 20% improvement (ACR20) and the Health Assessment Questionnaire-Disability Index (HAQ-DI). Other outcomes of note included measurements evaluating safety and immunogenicity, such as ACR50, ACR70, treatment-emergent adverse events (TEAEs), serious AEs, and discontinuation rates.
A total of 25 RCTs including 10,642 patients with RA were included in the review and analysis. The median baseline age was 53 years and the median proportion of female patients was 81%. All trials included patients with moderate-to-severe RA and most (64%) reported concomitant methotrexate treatment in both cohorts.
The biosimilars were equivalent with the biologic regarding both ACR20 response achievement and change of HAQ-DI scores at month 6 when considering the prespecified margins (24 RCTs with 10 259 patients; relative risk [RR], 1.01; 95% credible intervals [CrI], .98 to 1.04; τ2 = 0.000; HAQ-DI scores [14 RCTs with 5579 patients; standardized mean difference [SMD], −.04; 95% CrI, −.11 to .02; τ2 = 0.002], respectively). Overall, 79% of patients receiving biosimilars experienced ACR20 at month 6 compared with 78% of those receiving the biologic. A subgroup analysis demonstrated similar conclusions regarding ACR20 response and HAQ-DI.
Overall, biosimilar drugs were linked to similar safety and immunogenicity profiles when compared with the reference drugs. However, the risk of TEAEs and injection site reactions were lower in patients treated with biosimilars when compared with the reference drug. In total, 35.9% of patients receiving biosimilars and 39.6% of those in the reference drug cohort experienced TEAEs; 19.9% of patients in the reference biologic group experienced injection site reactions compared with only 6.2% of those in the biosimilars cohort.
Investigators noted limitations including a possible generalizability concern, as they did not assess biosimilars of all reference biologics currently available for the treatment of RA. Additionally, they characterized the equivalence between biosimilars and biologics as a combined group. Future researched should consider each reference molecule separately. As the safety data was sparse for some outcomes, more primary investigations with larger sample sizes are necessary.