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

Abstract Background Current treatments for rheumatoid arthritis (RA) and psoriatic arthritis (PsA) reduce disease activity but often fail to achieve sustained remission. The DocTIS programme has shown that additive anti-inflammatory effects in patients with arthritis can be achieved by combining tumour necrosis factor (TNF) and interleukin-6 (IL-6) inhibitor therapies. Objectives 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 two weeks for 8 weeks, escalating to weekly dosing in weeks 9–24 if well tolerated. The primary outcome is remission at 24 weeks (Clinical Disease Activity Index (CDAI) score of ≤ 2.8 in RA, and Disease Activity in PsA (DAPSA) score of < 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 7 participants per basket reach 24 weeks. Potential impact 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