Lower Adalimumab Biosimilar Withdrawal Rates Linked to Gender, Age

A retrospective, observational cohort study demonstrated 3 out of 4 patients continued treatment with the adalimumab biosimilar over a 2-year span, according to research published in Therapeutic Advances in Musculoskeletal Disease.¹ Risks of withdrawal were lower in older patients, males, those with a longer previous duration on the reference drug, and those who were prescribed the originator as the first biologic disease-modifying antirheumatic drug (bDMARD).

“Data on [the adalimumab biosimilar’s] efficacy and safety in routine care have been published to a limited extent in recent years, but data on treatment pathways over the long term are lacking,” wrote Xenofon Baraliakos, MD, PhD, head of rheumatology at the Rheumazentrum Ruhrgebiet Herne and professor of internal medicine and rheumatology at Ruhr-University Bochum, Germany, and colleagues. “Documentation of such treatment switches is essential in clinical practice, as clinical trials for switching from the originator bDMARD or other mode of action to a biosimilar DMARD are not part of the procedure provided by the European Medical Agency.”

According to previous research, drug retention rates of adalimumab in this patient population are hindered by a loss of efficacy, lack of effect, and adverse events. Additionally, approximately 50% of patients discontinued adalimumab within 5 years.² With the approval of the adalimumab biosimilar in October 2018, non-medical switching from the reference drug to the biosimilar has become increasingly popular as a part of routine practice in rheumatologic care. The numbers of biosimilar DMARDs have been steadily growing in the European market since their introduction in 2015.³

Investigators assessed the treatment trajectories over 2 years in patients with chronic inflammatory rheumatic diseases who were undergoing a non-medical switch from the adalimumab originator to the biosimilar using data from a third-level rheumatology center in Germany. Patients who switched from the reference drug to the biosimilar from October 2018 onwards were evaluated until September 2020.

Patients were characterized as “continued biosimilar adalimumab therapy,” “back-switch to originator adalimumab therapy,” “switch to another bDMARD therapy,” and “stopped bDMARD therapy/death/drop out.” Factors linked to treatment continuation were determined using Cox proportional hazards regression analyses.

Of the 121 patients with chronic inflammatory rheumatic diseases included in the study, most patients had axial spondyloarthritis (n = 74), rheumatoid arthritis (n = 24), and psoriatic arthritis (n = 17). Approximately one-third of patients were in remission at baseline and the median disease duration was 5 years.

Most (66.9%) continued treatment with the biosimilar over 2 years, with a treatment retention rate of 73.1%. A total of 21 patients (17.4%) switched back to the reference drug, mostly related to adverse events, and 8 patients (6.6%) switched to a different bDMARD, mostly due to a lack of efficacy.

A lower estimated risk of withdrawal was observed in patients who had a longer previous duration on the adalimumab originator (hazard ratio [HR]: .82; 95% confidence interval [CI]: .69 – .97). Conversely, a higher risk was reported in patients with higher C-reactive protein levels at baseline (HR: 1.18; 95% CI: 1.00 – 1.39). Older patients, males, and for those whom the original adalimumab was their first bDMARD had a lower risk of withdrawal.

Investigators noted the 2-year follow-up period and the study design strengthened the findings. However, the relatively small sample size and the large amount of missing disease activity information was a limitation.

“This is, to the best of our knowledge, the first study focusing on factors associated with withdrawal,” investigators concluded. “Our results corroborate those from other real-life studies examining treatment retention in chronic inflammatory rheumatic disease patients, although results are not completely comparable through to differences in study design.”

References

1. ^{Redeker I, Moustakis S, Tsiami S, et al. Treatment with adalimumab in patients with chronic inflammatory rheumatic diseases: a study of treatment trajectories on a patient level in routine care. Ther Adv Musculoskelet Dis. 2023;15:1759720X231197087. Published 2023 Sep 8. doi:10.1177/1759720X231197087}
2. ^{Neovius M, Arkema EV, Olsson H, et al. Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalimumab, etanercept and infliximab. Ann Rheum Dis 2015; 74: 354–360.}
3. ^{Park W, Hrycaj P, Jeka S, et al. A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study. Ann Rheum Dis 2013; 72: 1605–1612.}