P360 Safety and clinical efficacy of double switch from originator infliximab to biosimilars CT-P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicentre study

Abstract

Background Since infliximab (IFX) patent expiry in 2015, several IFX biosimilars have been licensed in EU for all indications, including inflammatory bowel diseases (IBD). IFX biosimilars currently available in Italy include CT-P13 and SB2, both of which demonstrated comparable efficacy, safety and immunogenicity with IFX originator in IBD patients. Safety and clinical efficacy of single switch from originator IFX to CT-P13 have also been confirmed in a prospective clinical trial. On the contrary, data regarding multiple therapeutic switching of IFX originator with CT-P13 and SB2 are currently lacking. Methods This study was aimed to evaluate the safety and efficacy of double switch from IFX originator to CT-P13 and subsequently to SB2 in patients with IBD. From November 2018 to May 2019, patients undergoing IFX double switch in 8 Centres in Lombardy were retrospectively analysed. The overall rate of IFX discontinuation, incidence and type of adverse events (AE) and proportion of patients on clinical remission over time were recorded. Data were compared with a control group of 66 IBD patients single switched from IFX originator to CT-P13. Results Fifty-two double-switched IBD patients were enrolled (63% M, mean age 41 years, 75% Crohn’s disease, 25% ulcerative colitis). Main indications for IFX therapy were moderate to severe disease (50%) and steroid-dependent disease (25%). The overall 24- and 48-week IFX discontinuation rates following second switch (CTP13->SB2) were 2% (95% CI 0–6%) and 14% (95% CI 3–25%), respectively. During a median follow-up of 40 weeks (18–48), 4 patients (12%) experienced a total of 6 AE (2 cutaneous, 2 infectious, 1 articular and 1 immunological), leading to IFX discontinuation in 3 cases (6%). No infusion reactions were observed. At week 24 following second switch, 49 (94%) patients were in clinical remission, the remaining 3 patients not being in remission already at the time of second switch. Only one patient lost response after week 24, 48 (92%) of patients being in clinical remission at the end of follow-up. No differences in IFX discontinuation, AE and clinical remission rates were found between double-switched and single-switched patients. No clinical parameters were found to predict safety and efficacy outcomes. Conclusion The study supports both safety and efficacy of the double switch from IFX originator to CT-P13 and SB2 in patients with IBD, and demonstrates its non-inferiority to a single switch strategy, with potential cost implications.

An observational study of switching infliximab biosimilar: no adverse impact on inflammatory bowel disease control or drug levels with first or second switch

“…However, very limited data are available with respect to switching between biosimilars in IBD with either long‐term outcomes or drug levels lacking 17,33,34 . We have shown that biosimilar‐to‐biosimilar switching does not have a negative influence in terms of infliximab trough levels and disease activity.…”

“…In a prospective real‐world observational study of 174 IBD patients ‘reverse switching’ from CT‐P13 to the originator Remicade, a small proportion (n = 14, 8%) had prior exposure to Remicade; no significant difference in clinical or infliximab trough level outcomes was seen by 24 weeks, regardless of prior exposure 36 . A recent abstract reported equivalent safety and efficacy data to Week 48 between 52 double‐switched IBD patients (originator to CT‐P13 to SB2) and 66 single‐switched controls (originator to CT‐P13) 33 . Likewise, similar safety and efficacy data were reported at 1 year between 24 double‐switched patients (originator to CT‐P13 to SB2) and a heterogeneous group commencing SB2 who were either naïve to anti‐TNF, infliximab, or being switched from CT‐P13 or originator 34 .…”

Outcomes after double switching from originator Infliximab to biosimilar CT‐P13 and biosimilar SB2 in patients with inflammatory bowel disease: a 12‐month prospective cohort study

“…In a recent French study performed in 140 patients with various IMIDs with a similar double switch, 132 (94.3%) were still treated with maintenance SB2 therapy at the end of the study 25 . Other observational studies of IBD and psoriasis have reported similar findings 22,26‐28 . Infliximab is an important immunogenic treatment, and the immunisation is responsible for a loss of response or an increase in adverse events.…”

“…25 Other observational studies of IBD and psoriasis have reported similar findings. 22,[26][27][28] Infliximab is an important immunogenic treatment, and the immunisation is responsible for a loss of response or an increase in adverse events. In our study, the rate of ADA did not increase after the switch (3.9% vs 2.8%, P = 0.75).…”

Biosimilar-to-Biosimilar Switching: What is the Rationale and Current Experience?

“…To the best of our knowledge, overall, there are seven real-world studies reported in which patients switched from one biosimilar to another. These studies provide some initial and preliminary support for the safety and efficacy of cross-switching, although, overall, the study durations are relatively short, sample sizes are comparatively small, and the existing data are limited to evaluations of infliximab biosimilars [1,[121][122][123][124][125][126]. Nevertheless, it should be considered that several adalimumab biosimilars have now been approved and are on the market in the EU-and presumably switches among them have occurred as matter of practical reality, yet reports of harm associated with adalimumab biosimilar cross-switching are conspicuously scarce [127].…”