A randomised open-label pilot trial comparing mycophenolate mofetil with no immunosuppression in limited cutaneous systemic sclerosis (MINIMISE-Pilot).

Abstract

Mycophenolate mofetil (MMF) is routinely used in early diffuse cutaneous systemic sclerosis (dcSSc) but not in limited cutaneous (lc)SSc. This may miss an opportunity to slow disease progression. MINIMISE-Pilot tested the feasibility of an open-label event-driven randomised trial of MMF vs no immunosuppression in lcSSc. We tested the feasibility of a trial evaluating the impact of MMF on a novel event-driven composite endpoint. The MINIMISE endpoint measures time to worsening of lcSSc determined by progressive lung fibrosis, pulmonary hypertension, scleroderma renal crisis, heart failure, severe gut involvement, major digital vascular complications or death. Prespecified 'Stop-Go' criteria were agreed. Subjects were stratified by ACA status. Recruitment was challenging. A total of 53 subjects were screened and 43 were randomised, 21 to the MMF arm. Since recruitment was <60 participants, MINIMISE-Pilot was terminated based upon the prespecified threshold for continuation. During the treatment period there were no clinical worsening endpoints. Adherence to MMF was generally high, with 19 participants (95%) being 100% adherent at week 1, decreasing to 9 participants (64%) at week 24. MINIMISE-Pilot achieved its goal as a feasibility trial, leading to early termination of the study due to low recruitment. The rationale and concept for this study remain very strong. However, our findings suggest that a randomised prospective trial across 12 sites in the UK with relatively short follow-up duration is not feasible. This will inform the design of future studies testing the benefit of MMF in lcSSc. Eudract (https://eudract.ema.europa.eu/) 2019-004139-21.