MRFF PROSPECT trial: A multi-centre, open-label, parallel-group randomised controlled trial of predicting disease-modifying anti-rheumatic drug dose tapering response in rheumatoid and psoriatic arthritis with economic evaluation: A preliminary report from NHMRC A3BC Centre of Research Excellence trial consortium

Aim: To compare down-titration strategies of biological and targeted synthetic Disease Modifying Anti-Rheumatic Drug (b/tsDMARD) therapies with usual care, in adults with well-controlled Rheumatoid and Psoriatic Arthritis (RA and PsA), with respect to efficacy, safety and cost effectiveness.

Method: Participants in stable low disease activity (LDA) on b/tsDMARD ± concurrent conventional synthetic DMARD (csDMARD) are being recruited from 10 sites in Australia. The planned sample size is 270. A 3-month run-in period will ensure disease activity stability, followed by block randomisation into 5 arms at baseline (~4:1 ratio of tapering to control group). A standardised disease-activity guided down-titration protocol is followed. The order of down-titration is also randomised for those on combination of b/tsDMARD + csDMARD. To better manage potential disease flares, a rescue protocol has been developed with patient research partner input.

Major outcomes include the proportion of persistent LDA, healthcare cost, change in disease activity, flare characteristics, change in therapy, radiographic progression, and biological predictors of remission/flare. Several sub-studies are being further investigated to identify cardiovascular impact, synovial tissue profile, the role of therapeutic drug monitoring, and the utility of patient decision aids in shared decision making. Laboratory analysis will be performed in the responder/non-responder subset to generate the multi-omic biological data, and machine learning will be applied for complex associations and prediction of down-titration success or failure.

Results: The trial is on early recruitment stage; as of Feb 2024, 30 patients have been recruited (27 RA, 3 PsA). 16 patients have been randomised with 2 in control arm and 14 in taper arms. Two minor disease flares were reported after down-titration; non-steroidal anti-inflammatory drug was prescribed to regain the disease control.

Conclusion: The study will be beneficial to advance the understanding of successful (or failure of) down-titration and to support clinical decision-making around b/tsDMARD tapering in adults with inflammatory arthritis.