Work

Subcutaneous versus intravenous ultra-low-dose rituximab in rheumatoid arthritis: a randomized controlled PK-PD non-inferiority trial

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: OBJECTIVES: Ultra-low-dose rituximab is an effective treatment in RA. S.c. administration may further facilitate rituximab treatment, reduce infection risk and reduce costs. This study aimed to assess non-inferiority of s.c. vs i.v. rituximab regarding pharmacokinetic and pharmacodynamic outcomes. METHODS: In this randomized, open-label, non-inferiority study, RA patients with stable low disease activity on ultra-low-dose rituximab (500 mg or 200 mg every 6 months) were 1:1 randomized to receive rituximab 336 mg s.c. or 200 mg i.v., stratified by previous rituximab dose. Primary outcome was non-inferiority of s.c. to i.v. rituximab, based on the estimated rituximab serum concentration area under the curve during the first 6 months (AUC0-6m), with a non-inferiority margin of 0.8. AUCs were estimated using PK modelling. Secondary outcomes included change in DAS28-CRP compared with a non-inferiority margin of 0.6. RESULTS: Thirty-five patients were randomized (17 i.v., 18 s.c.). The geometric mean ratio for AUC0-6m was 0.99 (90% CI 0.82-1.20), with minimal bias [mean predication error: i.v. 13.1 (1.86%); s.c. -3.40 (-0.47%)] but moderate random prediction error [root mean square error: i.v. 140 (19.8%); s.c. 142 (19.5%)] for the AUC estimates. Mean change in DAS28-CRP was non-inferior for s.c. rituximab (-0.39, 95% CI -0.77 to -0.004). CONCLUSION: Our data suggest non-inferior pharmacokinetics for s.c. rituximab; however, this cannot be definitively concluded due to uncertainty of the AUC estimates. Nevertheless, based on pharmacokinetic and pharmacodynamic parameters, ultra-low-dose s.c. rituximab could be an alternative for ultra-low-dose i.v. rituximab.

Source: Lara D. Veeken

DOI: 10.1093/rheumatology/keag420