Background/Purpose:  Biosimilar infliximab is registered in Europe for the same therapeutic indications as innovator infliximab. In 2015, four rheumatology departments in the Netherlands decided to switch from innovator infliximab to biosimilar infliximab based on comparable results in randomized controlled trials and favourable costs. Since data on switching to biosimilar infliximab in daily clinical practice were still scarce, we decided to collect clinical outcomes in a large observational multicentre prospective cohort study. The objective of our study was to investigate the effects of switching treatment from innovator infliximab to biosimilar infliximab on efficacy, safety and immunogenicity in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondylarthritis (SpA).

Methods:  Of all innovator infliximab-treated patients, 192/211 (91%) agreed to switch to biosimilar infliximab and were eligible for inclusion in this study. Primary outcome was change in DAS28-CRP (for RA and PsA) and BASDAI (for SpA) after 6 months of treatment. Secondary outcomes included C-reactive protein (CRP), adverse events and infliximab trough levels. Antidrug antibodies against infliximab were measured if the trough level was below 1 μg/ml.

Results:  In total, 75 patients with RA, 50 with PsA and 67 with SpA who switched treatment to biosimilar infliximab were included. 44/192 (23%) patients discontinued biosimilar infliximab during 6 months follow-up, respectively due to experienced inefficacy (n=35), adverse events (n=23) or an infusion reaction (n=2). Most frequently reported adverse events resulting in biosimilar discontinuation were fatigue (n=10), malaise (n=5) and headache (n=3). No serious adverse events occurred. 34 patients restarted innovator infliximab, 7 patients switched to another biological (2 adalimumab, 3 etanercept, 1 golimumab, 1 rituximab) and 3 patients maintained biological-free. In RA and PsA patients, mean DAS28-CRP remained stable from month 0 to 6: 2.19 [SD 0.89] to 2.22 [SD 0.84] (p=0.51). In SpA patients, mean BASDAI increased from 3.8 to 4.3 (change +0.5, 95% CI 0.12-0.89, p=0.01). CRP levels at baseline (median 1.5 mg/l [p25-p75:0-5]) and 6 months (median 1.0 mg/l [p25-p75: 0-5]) were not statistically different (p=0.60). To date, 138 baseline samples and 129 follow-up samples have been analyzed. Median infliximab trough levels were similar: 2.05 µg/ml versus 2.00 µg/ml (p=0.18). Antidrug antibodies were detected in 15/32 (47%) patients at baseline and in 10/26 (38%) patients after 6 months.

Conclusion:  In the majority of RA, PsA and SpA patients innovator infliximab can be switched to biosimilar infliximab without changes in efficacy, safety and immunogenicity during 6 months follow-up. However, 23% of the patients discontinued biosimilar infliximab, mainly due to a subjective increase in BASDAI score and/or adverse events, possibly explained by nocebo and/or attribution effects rather than pharmacological differences.

« Back to 2016 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-and-immunogenicity-outcomes-after-switching-treatment-from-innovator-infliximab-to-biosimilar-infliximab-in-rheumatic-diseases-in-daily-clinical-practice/