Sheppard, Rory, Gianatsi, Myrsini, Thomas, Ian, King, Sophie, Gillespie, David  ORCID: https://orcid.org/0000-0002-6934-2928, Pallmann, Philip ORCID: https://orcid.org/0000-0001-8274-9696, Marsal Barril, Sara and Choy, Ernest ORCID: https://orcid.org/0000-0003-4459-8609
2026.
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.
Rheumatology Advances in Practice
, rkag036.
10.1093/rap/rkag036
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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
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | In Press |
| Schools: | Schools > Medicine Research Institutes & Centres > Centre for Trials Research (CNTRR) |
| Publisher: | Oxford University Press |
| ISSN: | 2514-1775 |
| Date of First Compliant Deposit: | 23 March 2026 |
| Date of Acceptance: | 1 February 2026 |
| Last Modified: | 24 Mar 2026 10:00 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/185972 |
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