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.

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 30 mg/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.