Date: Sunday, November 10, 2019
Session Title: Epidemiology & Public Health Poster I: RA
Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
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.
To cite this abstract in AMA style:Lauret A, Moltó A, Abitbol V, Guterlann L, Conort O, Chast F, Goulvestre C, Le Jeunne C, Chaussade S, Roux C, Batteux F, Dougados M, Allanore Y, Avouac J. Effects of Successive Switches to Different Biosimilars Infliximab on Immunogenicity in Chronic Inflammatory Diseases in Daily Clinical Practice [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/effects-of-successive-switches-to-different-biosimilars-infliximab-on-immunogenicity-in-chronic-inflammatory-diseases-in-daily-clinical-practice/. Accessed March 28, 2023.
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