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

Abstract

Summary Background Biologics account for a significant cost in inflammatory bowel disease (IBD) management; however, switching from infliximab originator to its biosimilars has enabled cost saving without compromising disease control. The effects on IBD activity and infliximab trough levels of a second switch to another biosimilar are, however, uncertain. Aims To assess the effects on disease activity and infliximab trough levels associated with switching from infliximab biosimilar CT‐P13 to another biosimilar SB2 and compare outcomes in those switching for the first and second time. Methods IBD patients on CT‐P13, including some previously switched from originator, were prospectively followed during a switch to SB2. C‐reactive protein (CRP), trough infliximab level and clinical disease activity indices were collected at baseline, Infusion 3 or 4 (‘early’ after switch), and 1 year. Results One hundred eighty‐six patients (n = 99 second switch) on stable infliximab dosing underwent switching. Compared with baseline, there was no significant change in CRP, clinical disease activity scores or median trough infliximab level at the early time point among first‐switch (baseline vs early: 5.7 vs 6.6 µg/mL, P = 0.05) and second‐switch (4.3 vs 4.9 µg/mL, P = 0.07) patients nor at 1 year (median infliximab trough levels, baseline vs 1 year, in first‐switch [5.7 vs 5.7 µg/mL, P = 0.37] and second‐switch [4.3 vs 4.7 µg/mL, P = 0.06] patients). The proportion of patients in clinical remission did not significantly change at the early (92% vs 91% at baseline, P = 0.75) or 1 year (95% vs 91% at baseline, P = 0.16) time points. There was no significant difference in time to loss of response between patients switching for the first or second time (P = 0.69). Conclusions Switching from one infliximab biosimilar to another had no adverse impact on infliximab trough levels, and clinical and biochemical disease activity, regardless of whether switching for the first or second time.

Switching from One Biosimilar to Another Biosimilar of the Same Reference Biologic: A Systematic Review of Studies

“…The double-switch group from infliximab reference biologic to CT-P13 to SB2 had no statistically significant changes in AEs compared with the single biosimilar-to-biosimilar switch group [ 31 ]. Additionally, in 186 patients who switched from CT-P13 to SB2 (of whom 99 had previously switched from infliximab reference biologic to CT-P13 to SB2), no adverse impact was observed on infliximab trough levels and clinical and biochemical disease activity, regardless of whether switching for the first or second time [ 30 ]. De novo antidrug antibodies (ADAs) were found in < 4% of patients in either the single- or double-switch group [ 32 ].…”

“…In addition, studies with comparable follow-up periods (~12 months) [26,[29][30][31] found no loss in clinical responses at the middle [26,30,31] or conclusion of the studies [26,[29][30][31]. Mazza et al [31] found that the loss of response rate was ~15% at the conclusion of the trial, with no statistically significant differences between patients who switched from infliximab reference biologic to CT-P13 (n = 66) and those who switched from infliximab reference biologic to CT-P13 then to SB2 (n = 52); the observed loss of response was consistent with response loss with any infliximab treatment in patients with IBD [27,28].…”

Switching Among Biosimilars: A Review of Clinical Evidence

“…These preliminary data that did not suggest switching had an impact on drug persistence. Ten controlled cohort studies compared switching between two biosimilars vs. switching from originator to a biosimilar or vs. multiple switches, for example, from an originator to biosimilar A to biosimilar B ( Lauret et al, 2020 ; Gall et al, 2021 ; Hanzel et al, 2021 ; Khan et al, 2021 ; Lovero et al, 2021 ; Luber et al, 2021 ; Macaluso et al, 2021 ; Trystram et al, 2021 ; Lontai et al, 2022 ; Mazza et al, 2022 ). Eight were single-arm cohort studies, where participants switched from one biosimilar to another and outcome were compared before and after the switch ( Bouhnik et al, 2020 ; Gisondi et al, 2020 ; Kiltz et al, 2020 ; Mott et al, 2021 ; Peters et al, 2021 ; Piaserico et al, 2021 ; Ribaldone et al, 2021 ; Siakavellas et al, 2021 ).…”

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].…”

“…Lovero et al [121] have published these results in an abstract thus far. Luber et al [126] evaluated the effects of a switch from CT-P13 to SB2 on disease activity and trough levels in a 1-year, single-center, prospective observational study of 186 patients with IBD who were stabilized on CT-P13 therapy. Patients undergoing a non-medical switch from CT-P13 to SB2 for the first time (n = 87 [CD, n = 56; UC, n = 31]; mean±SD age, 30.7±12.3 years) or the second time (previously switched from infliximab originator; n = 99 [CD, n = 95; UC, n = 4]; mean±SD age, 33.2±12.5 years) were followed for changes in disease activity indices (Harvey Bradshaw Index [HBI] for CD; Simple Clinical Colitis Activity Index [SCCAI] for UC), infliximab trough levels, and C-reactive protein (CRP) from baseline to the time of the third or fourth infusion of SB2 and 1 year.…”