No Safety, Efficacy Differences Observed in Patients Switched to Adalimumab Biosimilar from Originator

Results of a study analyzing patients with inflammatory bowel disease (IBD) who replaced the adalimumab (ADA) originator with an ADA biosimilar as a cost measure noted no differences in safety and efficacy, according to literature published in Journal of Gastrointestinal and Liver Diseases.¹ However, replacement of ADA with a biosimilar in patients with ulcerative colitis (UC) should be more thoroughly evaluated.

“ADA, a fully human monoclonal antibody directed against soluble and membrane-bound TNF-α, has been shown to be largely effective and safe in the treatment of both Crohn‘s disease (CD) and UC patients,” investigators explained. “However, the approval for the use in clinical practice of ADA biosimilars in IBD is based on the concept of extrapolation of the results obtained in other diseases such as rheumatoid arthritis and psoriasis. This type of speculation is unique to biosimilars, and the preliminary evaluation has given us some reservations about the concept of extrapolation.”

The safety and efficacy of 4 ADA biosimilars (SB5 [Imraldi], APB 501 [Amgevita], GP2017 [Hyrimoz], and MSB11022 [Idacio]) was compared in a real-life setting in adult patients with IBD living in Italy after switching from the originator for a non-medical reason in the multicenter, retrospective, post-hoc analysis study. Clinical, laboratory, and endoscopic data were evaluated. ADA biosimilars were administered subcutaneously at 40 mg every 2 weeks post switch. The primary endpoints were safety as well as the maintenance of clinical remission, which was defined as no need for ADA optimization or the addition of immunosuppressants or steroids.

Of the 153 patients enrolled in the study, 127 had a CD diagnosis and 26 had UC. Clinical remission was maintained in most (81%, n = 124/153) patients during a follow-up period of 12 (6-24) months, with 84.6% in the ABP 501 cohort, 78.5% in the SB5 cohort, 66.7% in the GP2017 group, and 100% of those receiving MSB11022 (p = 0.549).

Loss of remission was significantly higher in patients with UC (38.5%, n = 10/26) when compared with patients with CD (14.9%, n = 19/127k, p < 0.026). No significant difference was observed between the 4 biosimilars.

ADA biosimilar optimization was needed in 3.3% (n = 5/153) of patients and 7.1% (n = 9) switched back to the ADA originator. Adverse events (AEs) occurred in 7.9% (n = 12) of patients; however, the majority of AEs were categorized as mild with the exception of 1 severe AE (leukopenia) which was reversed after drug withdrawal. The most frequent AE was itch/pain at injection site.

The study was strengthened by the real-life study design and large cohort of patients, which reflects actual clinical practice. However, investigators were unable to draw conclusions regarding patients in the GP2017 and MSB11022 groups due to the limited number of patients treated with these dugs and the short follow-up period. The retrospective design did not allow for the same follow-up for all patients. Lastly, the addition of an ADA originator group would have been helpful in understanding differences in long-term management in this patient population.

“We should consider the dark side of the medal: our population included patients in stable remission under ADA originator treatment, and the rate of about 20% of patients losing remission, together with a significant rate of successful switch back to the ADA originator, is a finding that requires careful evaluation in prospective studies, also for the ethical implications,” investigators concluded. “This is particularly relevant for UC patients, who seem to have the worst performance when the ADA originator was replaced for a non-medical reason.”

Reference:

Tursi A, Mocci G, Cuomo A, et al. Replacement of Adalimumab Originator to Adalimumab Biosimilar for a Non-Medical Reason in Patients with Inflammatory Bowel Disease: A Real-life Comparison of Adalimumab Biosimilars Currently Available in Italy. J Gastrointestin Liver Dis. 2022;31(4):411-416. Published 2022 Dec 16. doi:10.15403/jgld-4608