Background/Purpose: Blinded transitioning from originator infliximab (INX) to biosimilar CT-P13 was not inferior to continuing INX treatment.¹ Open label mandatory transitioning resulted in a  slightly lower 1-year CT-P13 retention rate than for INX in a historical cohort.² However, non-mandatory transitioning might be preferred above mandatory. Therefore, we assessed the effects of open label non-mandatory transitioning from originator etanercept (ENB) to biosimilar SB4 on drug survival and effectiveness in rheumatic diseases in daily practice.

Methods: In 2016, 642 ENB treated patients were asked to transition to SB4 by a structured implementation strategy with opt-out option. Consenting patients were eligible for inclusion in our study [BIO-SPAN]. ENB treated patients in 2014 were recruited as historical cohort. The 6-months retention rate in the two cohorts was compared. Multivariable Cox regression analysis was used to calculate HR for discontinuation adjusted for baseline characteristics (age/gender/diagnosis/ENB treatment duration/ENB dose interval/csDMARD/CRP) and with a robust variance estimator to account for repeated subjects. Reasons for discontinuation and change in DAS28-CRP, BASDAI and CRP after 6 months were assessed.

Results: 635 (99%) patients agreed to transition to SB4 of whom 625 patients (433 RA, 128 PsA, 64 AS; 55% women; age 57 (14) years) were included in the transition cohort. 600 patients were included in the historical cohort. Crude 6-months retention rates of SB4 in the transition cohort and ENB in the historical cohort were: 90% (95%CI 88%-93%) vs 92% (95%CI 90%-94%). The transition cohort had a significantly higher relative risk of discontinuation than the historical cohort (adjusted HR 1.57, 95%CI 1.05–2.36). Reasons for discontinuing SB4 (n=60, 10%) and ENB (n=46, 8%) were: lack of effect (43% vs 61%), adverse events (47% vs 28%), malignancy (3% vs 4%), pregnancy (4% vs 4%) and other (3% vs 3%). In the transition cohort, 17 patients restarted ENB, 32 patients switched to another biologic and 11 patients maintained biologic-free. DAS28-CRP, BASDAI and CRP were not statistically different between baseline and month 6 in the transition cohort. Due to a slightly lower baseline CRP (1 [0-5] vs 3 [1-5], p<0.001) and DAS28-CRP (1.9 [1.5-2.6] vs 2.1 [1.6-2.9], p<0.001) changes in CRP (0.5 (12) vs -1.5 (14), p=0.01) and DAS28-CRP (-0.01 (0.93) vs -0.26 (-0.99), p<0.001) at month 6 favored the historical cohort.

Conclusion: Open label non-mandatory transitioning from ENB to SB4 showed a statistically significantly but clinically not relevant lower retention rate compared to a historical cohort, similar to retention seen after mandatory INX transitioning. Non-mandatory transitioning, when executed optimally, might therefore be an attractive alternative to mandatory transitioning.

References: ¹Jørgensen KK. Lancet 2017 ²Glintborg B. Ann Rheum Dis 2017