Discontinuation of Biosimilar Infliximab Associated With Subjective Complaints
Safety and effectiveness of CT-P13 were assessed in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.
After open-label transitioning from originator infliximab to biosimilar infliximab (CT-P13), approximately one-quarter of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) discontinued the biosimilar during 6 months of follow-up, due mainly to an increase in subjective health complaints, which might be explained by nocebo and/or incorrect causal attribution effects, according to the results of a recent multicenter, prospective Dutch cohort study published in Arthritis & Rheumatology.1
Of 222 patients treated with originator infliximab, 192 agreed to transition to CT-P13 and were included in the analysis. The primary outcome was change from baseline in disease activity at 6 months (± 2 months). Disease activity was assessed with the Disease Activity Score 28-joint count C-reactive protein (DAS28-CRP) and its individual components for patients with RA and PsA, and with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for those with AS.2,3 Secondary outcomes included CRP level, erythrocyte sedimentation rate (ESR), (anti-) infliximab levels, and safety.
Overall, 24% (47 of 192) of patients discontinued CT-P13 during the 6-month follow-up. Of these, 37 patients restarted the originator infliximab, 7 switched to another biologic agent, and 3 were maintained biologic-free. Of the 32 reported adverse events, 25 (78%) could be classified as subjective health complaints.
Based on univariate regression analysis, shorter originator infliximab infusion interval, higher DAS28-CRP, higher DAS28-ESR, higher swollen joint count, and higher patients' global disease activity at baseline were all significantly associated with CT-P13 discontinuation. In the multivariate Cox analysis that included only patients with RA and PsA, shorter originator infliximab infusion interval (in weeks) was the only significant predictor of discontinuation of CT-P1 (hazard ratio, 0.77; 95% CI: 0.62-0.95).
In the intention-to-treat analysis, mean DAS28-CRP in patients with RA and PsA remained stable from baseline to 6 months (95% CI: -0.1 to 0.2). In patients with AS, mean BASDAI increased from 3.8 to 4.3 (95% CI: 0.1-0.9).
The investigators concluded that based on the substantial discontinuation rate of CT-P13 because of subjective health complaints, communication seems to be the determining factor in the success of transitioning to a biosimilar in daily clinical practice.
- Tweehuysen L, van den Bemt BJF, van Ingen IL, et al. Subjective complaints as main reason for biosimilar discontinuation after open label transitioning from originator to biosimilar infliximab [published online October 18, 2017]. Arthritis Rheumatol. doi: 10.1002/art.40324
- Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38(1):44-48.
- Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994;21(12):2286-2291.