Efficacy and Safety of Switching from Innovator Rituximab to Biosimilar CT-P10 Compared with Continued Treatment with CT-P10: Results of a 56-Week Open-Label Study in Patients with Rheumatoid Arthritis

Abstract

BackgroundCT-P10 is a biosimilar candidate of innovator rituximab (RTX) that demonstrated a comparable clinical profile to RTX in a phase I randomized controlled trial (RCT) in rheumatoid arthritis (RA) (ClinicalTrials.gov identifier: NCT01534884).ObjectiveThis open-label extension (OLE) study (NCT01873443) compared the efficacy and safety of CT-P10 in patients with RA who received CT-P10 from the outset (i.e., from the start of the RCT and also in the OLE; ‘maintenance group’) with those who received RTX during the RCT and switched to CT-P10 during the OLE (‘switch group’).MethodsPatients who completed the RCT were recruited. Based on the Disease Activity Score using 28 joints (DAS28) and predefined safety criteria, patients could receive up to two courses of CT-P10 during the OLE. Efficacy [DAS28 and European League Against Rheumatism (EULAR) response], safety and immunogenicity were assessed.ResultsEighty-seven patients were enrolled; 58 and 29 had previously received CT-P10 or RTX, respectively, in the RCT. Of these, 38 (65.5%) and 20 (69.0%) were treated with CT-P10 in the OLE and therefore comprised the maintenance and switch groups, respectively. The mean change in DAS28-erythrocyte sedimentation rate (ESR) from baseline (week 0 of RCT) at week 24 of the first OLE treatment course in the maintenance and switch groups was −2.7 and −2.4, respectively. The proportion of patients with good/moderate EULAR responses was also comparable between groups. Antidrug antibodies were detected in 13.2 and 15.0% of patients in the maintenance and switch groups, respectively, at week 24 of the first OLE course. CT-P10 treatment was well-tolerated when administered for up to 2 years or after switching from RTX.ConclusionIn this study population, comparable efficacy and safety profiles were observed in patients who switched from RTX to CT-P10 and those maintained on CT-P10 throughout treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s40259-017-0233-6) contains supplementary material, which is available to authorized users.

Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review

“…Of the 23 clinical, non-medical switching studies (Table 1) [53, 55, 56, 60, 61, 69, 70, 73–75, 81, 82, 84–86, 91–99, 101–104], 22 reported data on main efficacy parameters in switched versus non-switched or pre-switch versus post-switch groups. The originator biologics/biosimilars assessed were infliximab (six studies [53, 55, 56, 61, 69, 70, 73]), erythropoietin-stimulating agents (ESAs) (four studies [74, 75, 81, 82]), filgrastim [93–95] (three studies), insulin [84–86], adalimumab [96–98], rituximab [60, 99] and etanercept [101–103] (two studies each), and genotropin [83, 92] and follicle stimulating hormone [104] (one study each).…”

“…The originator biologics/biosimilars assessed were infliximab (six studies [53, 55, 56, 61, 69, 70, 73]), erythropoietin-stimulating agents (ESAs) (four studies [74, 75, 81, 82]), filgrastim [93–95] (three studies), insulin [84–86], adalimumab [96–98], rituximab [60, 99] and etanercept [101–103] (two studies each), and genotropin [83, 92] and follicle stimulating hormone [104] (one study each).…”

“…Of these, 15 included statistical analyses of disease activity or patient outcomes in switched versus non-switched groups, pre-switch versus post-switch groups or observed versus predicted outcomes [53, 60, 61, 73, 74, 81, 82, 84–86, 91–95, 99], with five studies specifying a formal equivalence or non-inferiority margin [53, 74, 81, 82, 95]. There were no statistically significant differences between groups (based on P  < 0.05 or predefined acceptance ranges), with the exception of a significant weight gain that was observed in patients with type 1 diabetes mellitus switched to biosimilar compared with patients remaining on originator insulin (+ 1.0 kg vs + 0.2 kg, respectively; P  < 0.05) in the open-label extension of the ELEMENT 1 RCT, although the range of weight changes was wide in both groups [84].…”

“…The relative frequency of ADAs in biologic originator and biosimilars was reported in 27 studies, of which 18 were clinical studies [53, 55, 56, 60, 61, 69, 70, 73, 81, 82, 84–86, 91, 92, 95–99, 101–104] and nine were observational [46–48, 52, 57, 63, 67, 68, 71, 105]. In 26 studies (17 clinical: follow-up 12–52 weeks [53, 55, 56, 60, 61, 69, 70, 73, 81, 82, 84, 85, 91, 92, 95–99, 101–103]; nine observational: follow-up 6–13 months [46–48, 52, 57, 63, 67, 68, 71, 105]), there were either no cases of ADAs, or the incidence of ADAs was similar in both groups.…”

“…80, based on study design)RTX RP, 24 weeks, or BCD-020, 24 weeksBCD-020 24 weeks or RTX RP 24 weeksRTX RP/RTX RP vs RTX RP/BCD-020, ACR20 at week 48: 92.3 vs 77.8% ( P  = 0.25); BCD-020/RTX RP vs BCD-020/BCD020: 89.3 vs 96.0%, ( P  = 0.61). RTX RP/RTX RP, RTX RP/BCD-020, BCD-020/RTX RP, BCD-020/BCD-020 ACR70 at week 48: 34.6, 40.7, 39.3, 40.0%AEs, RTX RP/RTX RP, RTX RP/BCD-020, BCD-020/RTX RP, BCD-020/BCD-020: 38, 57, 63, 44%RTX RP/RTX RP, RTX RP/BCD-020, BCD-020/RTX RP, BCD-020/BCD-020: 0 vs 0 vs 0 vs 4%Park et al 2017 [60]With rheumatoid arthritis ( N  = 58)20Rituximab, up to 72 weeks (study also included patients on CT-P10 throughout, with no switch)CT-P10, up to 56 weeksCT-P10/CT-P10 vs rituximab/CT-P10, mean change at week 24 vs baseline, after 1st course, DAS28-CRP: − 2.2 ± 1.15 vs − 2.2 ± 1.16 ( P NS); DAS28-ESR: − 2.7 ± 1.17 vs − 2.4 ± 1.33 ( P NS). Percentage achieving good or moderate EULAR-ESR and EULAR-CRP responses similar between groups for each time point (week 8, 16 and 24)CT-P10/CT-P10 vs rituximab/CT-P10, AE: 24 vs 20%; SAE: 3 vs 5%; infusion-related reaction: 3 vs 5%; infection: 8 vs 10%CT-P10/CT-P10 vs rituximab/CT-P10: 13 vs 15% (all since pre-switch).…”