Study: No Differences Between Biosimilar TNFα-inhibitor, Reference Products for Long-Term Survival

There were no significant differences found between biosimilar TNFα-inhibitor and the reference products for long-term survival due to either inefficacy or adverse events, according to results of a study published in The Journal of Rheumatology. The reference products and biosimilars included products with adalimumab (Humira; AbbVie) and etanercept (Enbrel; Amgen), both anti-rheumatic drugs that are administered subcutaneously.

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According to the authors of the study, some observational studies had lower retention rates for biosimilars after switching, and real-world studies showed some increase in adverse events (AEs) with biosimilars. Investigators of the study aimed to determine the differences in overall and cause-specific drug discontinuation between biosimilar etanercept and adalimumab and the originators in clinical practice in Spain. The secondary objective of the investigators included factors that influenced drug survival.

Investigators used a multicenter prospective observational registry, BIOBADASER, which included patients with rheumatic disease and were on biological disease-modifying antirheumatic drugs (bDMARD) or targeted synthetic DMARD. Individuals in the study had rheumatoid arthritis (RA), juvenile idiopathic arthritis, ankylosing spondylitis, other non-psoriatic spondylarthritis (SpA), or psoriatic arthritis. Individuals included also were on treatment for at least 3 months and started therapy from January 2016 for etanercept or January 2018 for adalimumab until October 2023, according to the study authors. Each treatment course was counted, therefore, individuals who switched between either adalimumab or etanercept or between originator and biosimilar could be counted in both groups.

Demographics and clinical data were analyzed, including diagnosis, age at the time of treatment initiation, gender, body mass index, tobacco use, disease duration, follow-up time, concomitant treatment with conventional synthetic DMARD and corticosteroids, line of treatment, and reason for drug withdrawal.

Investigators included a total of 4723 treatment courses, with 2991 being adalimumab and 1732 being etanercept. Of the 4162 patients, approximately 16.41% received the originator and 87.22% received a biosimilar. Further, 151 patients received both the biosimilar and originator and 256 were treated with both adalimumab and etanercept.

Investigators found that 36.42% of patients had discontinued treatment, with those on the originator discontinuing more frequently than the biosimilars at 53.32% and 33.37%, respectively. Approximately 60.35% discontinued treatment due to inefficacy, followed by 17.85% due to AEs. However, biosimilars were more frequently discontinued due to inefficacy and AEs while the originators were more frequently discontinued due to remission, according to the study authors. Compared with patients who had RA, patients with SpA had lower risk of discontinuation, according to the study authors.

Factors that increased the risk of discontinuation included female sex, obesity, and second and third or subsequent lines of treatment. The use of concomitant methotrexate and disease duration were also associated with lower risk of discontinuation. When investigators evaluated the cause-specific reasons for discontinuation, they found that there were no significant differences in the risk of discontinuation between the biosimilar and the originator.

The study authors stated that limitations could include biased clinicians in using biosimilars, which could affect the prescribing rates. Further, even though there the invesitgators accounted for differences in the risk of drug discontinuation, it is possible that residual confounding factors might not have been included.

Reference

Martínez-Vidal MP, Fernández-Carballido C, Otero-Varela L, et al. Long-Term Survival Of Subcutaneous Biosimilar TNFα Inhibitors Compared To Originators: Results From A Multicenter Prospective Registry. J Rheumatol. Published online June 1, 2024. doi:10.3899/jrheum.2024-0001