Nipocalimab and certolizumab combination therapy in participants with active rheumatoid arthritis despite prior treatment with advanced therapies: results from the phase 2a DAISY-RA study

Abstract

Objectives: To investigate the efficacy, safety, pharmacokinetics, immunogenicity and pharmacodynamics of combination therapy with nipocalimab and certolizumab in participants with active rheumatoid arthritis (RA) despite treatment with advanced therapies.

Methods: In this phase 2a study, participants were randomised 3:2 to receive combination therapy with nipocalimab (intravenous 30mg/kg) and certolizumab (subcutaneous 400 mg at weeks 0, 2, 4, then 200 mg) or certolizumab monotherapy every 2 weeks from weeks 0 to 24. The primary endpoint was change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) at week 12. Other outcomes were assessed through week 30.

Results: 103 participants were enrolled (combination therapy/monotherapy, n=62/41). At week 12, the primary endpoint was similar between groups (least squares mean 90% CI-1.92 (-2.48 to-1.36) vs-1.86 (-2.44 to-1.28); p=0.822). Secondary endpoints were also similar between groups, although numerically higher proportions of participants treated with combination therapy versus monotherapy achieved >= 50% response in American College of Rheumatology criteria (ACR50), DAS28-CRP <2.6 and DAS28-CRP <= 3.2 at week 12. Serious adverse events were reported in 11.3% of participants in the combination therapy group and 2.4% in the monotherapy group. In combination with certolizumab, nipocalimab exhibited nonlinear pharmacokinetics with accelerated clearance and substantially, reversibly reduced serum immunoglobulin G, including anticitrullinated protein antibody levels. Conclusions: Combination therapy of nipocalimab with certolizumab showed a similar outcome in the primary endpoint and secondary endpoints compared with certolizumab monotherapy in participants with active RA.