Decision on Optimal Combinatorial Therapies in Immune-mediated inflammatory diseases using Systems approaches (DocTIS): protocol for a single-arm, adaptive basket trial in rheumatoid and psoriatic arthritis.

OBJECTIVES

Current treatments for rheumatoid arthritis (RA) and psoriatic arthritis (PsA) reduce disease activity but often fail to achieve sustained remission. The Decision on Optimal Combinatorial Therapies in Immune-mediated inflammatory diseases using Systems approaches (DocTIS) program has shown that additive anti-inflammatory effects in patients with arthritis can be achieved by combining tumour necrosis factor (TNF) and interleukin (IL)-6 inhibitor therapies. The goal was to provide proof-of-principle evaluation of whether combining TNF and IL-6 inhibitors shows a signal of activity on remission outcomes in RA and PsA.

METHODS

This is a single-arm, multicentre, adaptive basket trial recruiting 20 patients with RA and 20 with PsA and including 24 weeks of treatment and 10 weeks of safety follow-up. Eligible participants on TNF for ≥6 weeks will proceed with the addition of IL-6 inhibitor (tocilizumab) at 162 mg every 2 weeks for 8 weeks, increasing to weekly dosing in weeks 9-24 if well tolerated. The primary outcome is remission at 24 weeks (Clinical Disease Activity Index score ≤2.8 in RA and Disease Activity in PsA score <4). Secondary outcomes include safety, tolerability and disease activity assessments. Using Simon's two-stage design (80% power, one-sided α = 0.10), the trial aims to detect an increase in remission (10% to 30%). An interim futility analysis will occur after seven participants per basket reach 24 weeks.

CONCLUSION

Findings from this proof-of-principle study will inform the feasibility and design of future randomised trials evaluating combination biologic therapy in inflammatory arthritis.

STUDY REGISTRATION: www.isrctn.com; ISRCTN50666516.