Comparing immunogenicity and safety following transition from reference rituximab to biosimilar rituximab (DRL_RI) in patients with rheumatoid arthritis: a randomized, double-blind, phase 3 study

Arthritis Res Ther. 2024 Dec 21;26(1):225. doi: 10.1186/s13075-024-03456-w.

Abstract

Objectives: To assess immunogenicity and safety in patients with active rheumatoid arthritis (RA) transitioning from rituximab [US-licensed rituximab: Reference Product (RP); EU-approved rituximab: Reference Medicinal Product (RMP)] to DRL_RI (proposed rituximab biosimilar), in comparison to those continuing on RP/RMP.

Methods: This double-blind, randomized, Phase 3 study included 140 RA patients having prior exposure to RP/RMP; transitioned to DRL_RI (n = 70) or continued with RP/RMP (n = 70) for two 1000 mg infusions on Days 1 and 15. Assessments included Time-matched Rituximab Concentration (TMRC), anti-drug antibodies (ADAs), neutralizing antibodies (NAbs) and ADA titre over 12 weeks, and safety follow-up till 26 weeks.

Results: The mean age of subjects was 59.8 years (range: 24, 86) and the mean BMI was 27.76 kg/m2 (range: 17.5, 52.0). Incidence of ADA after dosing was low in both groups: 1.4% in DRL_RI group on Day 15, Week 8, and Week 12; and 2.9% in RP/RMP group at Week 12. Only 1 patient in DRL_RI group was positive for NAbs at Week 8. ADA titre values did not significantly differ between the two groups. The time-matched rituximab concentration was comparable between groups, indicating no interference for immunogenicity assessment. Treatment-emergent adverse events (TEAEs) were reported by 34.3% and 38.6% patients, respectively, in DRL_RI and RP/RMP groups. Incidences of TEAEs that were drug-related, leading to treatment discontinuation, grade ≥ 3, or serious, were also comparable.

Conclusion: Immunogenicity was low and comparable in RA patients transitioning to DRL_RI or continuing on RP/RMP. The overall safety profile in patients transitioning to DRL_RI did not appear to differ in frequency, severity, or quality from patients continuing on RP/RMP and was in line with the known safety profile of rituximab.

Trial registration: ClinicalTrials.gov identifier NCT0426877 EudraCT:2019-002810-37 US IND 112766.

Keywords: Biosimilar; Immunogenicity; Rheumatoid arthritis; Rituximab; Safety; Switching; Transition.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III
  • Multicenter Study
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antirheumatic Agents* / administration & dosage
  • Antirheumatic Agents* / adverse effects
  • Antirheumatic Agents* / immunology
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / immunology
  • Biosimilar Pharmaceuticals* / administration & dosage
  • Biosimilar Pharmaceuticals* / adverse effects
  • Biosimilar Pharmaceuticals* / therapeutic use
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Rituximab* / administration & dosage
  • Rituximab* / adverse effects
  • Rituximab* / therapeutic use
  • Young Adult

Substances

  • Rituximab
  • Biosimilar Pharmaceuticals
  • Antirheumatic Agents