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

Objectives:

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 feasibility of an open-label event-driven randomised trial of MMF versus no immunosuppression in lcSSc.

Methods:

We tested feasibility of a trial evaluating 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. Pre-specified “Stop-Go” criteria were agreed. Subjects were stratified by anticentromere antibody (ACA) status.

Results:

Recruitment was challenging. 53 subjects were screened and 43 randomised, 21 to MMF arm. Since recruitment was below 60 participants, MINIMISE-Pilot was terminated based upon the prespecified threshold for continuation. During the treatment period there were no clinical worsening clinical 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.

Conclusion:

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 UK with relatively short follow-up duration is not feasible. This will inform design of future studies testing benefit of MMF in lcSSc.