Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results

Abstract

Objectives: SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage.

Methods: In this phase III, double-blind, parallel-group, multicentre study, patients with moderate to severe RA despite MTX were randomized (1:1) to receive 3 mg/kg of either SB2 or INF at 0, 2, 6 and every 8 weeks thereafter. Dose escalation by 1.5 mg/kg up to a maximum dose of 7.5 mg/kg was allowed after week 30. Efficacy, safety and immunogenicity were measured at each visit up to week 54. Radiographic damage evaluated by modified total Sharp score was measured at baseline and week 54.

Results: A total of 584 patients were randomized to receive SB2 (n = 291) or INF (n = 293). The rate of radiographic progression was comparable between SB2 and INF (mean modified total Sharp score difference: SB2, 0.38; INF, 0.37) at 1 year. ACR responses, 28-joint DAS, Clinical Disease Activity Index and Simplified Disease Activity Index were comparable between SB2 and INF up to week 54. The incidence of treatment-emergent adverse events and anti-drug antibodies were comparable between treatment groups. Such comparable trends of efficacy, safety and immunogenicity were consistent from baseline up to 54 weeks. The pattern of dose increment was also comparable between SB2 and INF.

Conclusion: SB2 maintained similar efficacy, safety and immunogenicity with INF up to 54 weeks in patients with moderate to severe RA. Radiographic progression was comparable at 1 year.

Trial registration: ClinicalTrials.gov (http://clinicaltrials.gov; NCT01936181) and EudraCT (https://www.clinicaltrialsregister.eu; 2012-005733-37).

Keywords: Flixabi; Remicade; Renflexis; Sharp score; biosimilar; infliximab; monoclonal antibody; radiographic progression; rheumatoid arthritis; tumour necrosis factor blocker.

Fig. 1

Disposition flow chart of the study population Eight patients’ data from sites in Eastern Ukraine were excluded from the analysis due to regional issues (n = 4 in SB2, n = 4 in INF). INF: reference infliximab.

Fig. 2

Cumulative probability of change in the mTSS at week 54 (full analysis set) INF: reference infliximab.

Fig. 3

Improvement of disease activity and remission rates (full analysis set) (A) Mean DAS28, CDAI and SDAI up to week 54. (B) Disease activity classification (remission and LDA). Remission is defined as DAS28 <2.6, CDAI ≤2.8 or SDAI ≤3.3 and LDA is defined as DAS28 ≥2.6–<3.2, CDAI ≤10.0 or SDAI ≤11.0. The data above each bar are the total sum of remission and LDA. INF: reference infliximab.

Fig. 4

ACR20, 50 and 70 response rates up to week 54 (full analysis set) INF: reference infliximab.

Fig. 5

Analysis of ACR20 response rate and infusion-related reaction incidence by 54 week ADA status (A) ACR20 response rate at week 54 in the PPS set by 54 week overall ADA status. (B) The patients with infusion-related reaction up to week 54 in the SAF set by 54 week overall ADA status. INF: reference infliximab.