Background/Purpose: To determine whether the successive switches from innovator infliximab to a first then a second biosimilar infliximab, or from a first to a second infliximab biosimilar, increase the risk of immunogenicity during a 3-year observation period.

Methods: This is a usual care study performed in the Rheumatology, Gastroenterology and Internal Medicine departments of Cochin Hospital, Paris, France. Two independent cohorts were constituted; Cohort 1 included patients on maintenance therapy with the original treatment who successively switched to CT-P13 in October-December 2015 then to SB2 in December 2017. Cohort 2 included biologic-naïve patients who received CT-P13 starting from November 2015 before being switched to SB2 in December 2017.The end of the observation period was December 2018. Immunogenicity was defined by the detection of positive anti-drug antibodies (ADA >10 ng/mL), at least at two consecutive time points.

Results: Cohort 1 consisted on 265 patients on maintenance therapy with innovator infliximab who switched to CT-P13. Then, 140 patients switched to SB2, 26 remained treated with CT-P13, and innovator infliximab was re-established in 55 patients. 30 patients (16 females) had positive ADA at baseline visit (11.3%), before the switch to CT-P13. These patients were more likely to have a BMI >30 (45% vs. 17%, p< 0.001) and received less innovator infliximab infusions (28±20 vs. 40±25 infusions, p=0.012) than patients without ADA. Among the 235 ADA-free patients  at baseline, 20 patients developed ADA during the observation period, corresponding to a rate of 3 for 100 patient years. The mean time to positive ADA detection was 21±14 months (range: 1-37 months). Kaplan Meyer curve illustrating immunogenicity-free survival showed no influence of the number of biosimilars infliximab received on immunogenicity (Figure 1A). Cohort 2 consisted of 44 biologic-naïve patients who initiated CT-P13. Among these patients, 29 switched to SB2, 4 remained treated with CT-P13 and 11 discontinued the treatment before the second switch. 11/44 (25%) patients developed ADA during the observation period, corresponding to a rate of 14 for 100 patients years. Only a single patient developed ADA after the switch to SB2. The mean time to positive ADA detection was 13±11 months (range: 1-31 months). The risk of treatment discontinuation was significantly higher in patients with positive ADA in both cohorts (cohort 1: Hazard Ratio, HR: 2.37, 95% CI 1.38-4.05, p=0.002 and cohort 2: HR: 2.79, 95% CI 1.04-7.52, p=0.042) (Figure 1B-C).Predictors of immunogenicity were only identified in cohort 2: a BMI >30 at baseline visit and mean infliximab through levels < 2 mg/mL from baseline visit to ADA detection were predictive of the development of ADA with HR (95% CI) of 5.54 (1.30-23.65) and 5.53 (1.30-23.43), respectively. The retention rate of infliximab was 58% (154/265) in cohort 1 and 66% (29/44) in cohort 2 at the end of observation period (Figure 1D-E).

Conclusion: Immunogenicity was not favored by switches to biosimilars infliximab in our study. Thus, immunogenicity does not constitute a barrier to interchangeability between biosimilars infliximab in chronic inflammatory diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effects-of-successive-switches-to-different-biosimilars-infliximab-on-immunogenicity-in-chronic-inflammatory-diseases-in-daily-clinical-practice/