FRI0445 A randomised controlled trial to compare the efficacy of oral mycophenolate mofetil with placebo in patients with systemic sclerosis related early interstitial lung disease
Authors: G. Naidu, S. Sharma, V. Dhir, S. Dhooria, A. Sinha, A. Mb, S. Jain
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Previous studies showed benefit of immunosuppressants in moderate to severe ILD in systemic sclerosis (SSc).<sup>1,2</sup> Initiation of immunosuppression early in the course of SSc-ILD might help in halting disease process and improve long term morbidity and mortality. <h3>Objectives</h3> Aim of the study was to determine efficacy and safety of mycophenolate mofetil (MMF) in treating early and mild SSc-ILD (ILD on HRCT, FVC ≥70% predicted). Primary outcome was to compare the change in FVC after 6 months of therapy with MMF or placebo. Secondary outcomes were change in SF-36v2, Mahler dyspnoea index (MDI) and adverse events profile of MMF and placebo. <h3>Methods</h3> This was a double-blind, randomised, placebo-controlled trial conducted at a tertiary care centre in north India. SSc-ILD patients with FVC ≥70% and aged &gt;18 years were randomised to receive either MMF (up to 2 g/day) or placebo for 6 months. FVC, DLCO, MRSS, SF36v2, MDI and 6 min walk distance (6MWD) were noted at baseline and 6 months. Outcome was categorised into improved/stabilised (any increase in FVC or fall in FVC &lt;10% from baseline) and worsened (fall in FVC ≥10% from baseline). Trial was approved by the institute ethics committee and was registered at ClinicalTrials.gov (NCT02896205). <h3>Results</h3> Forty-one subjects were included in the study (20 MMF and 21 placebo). Mean age was 40.3±10.1 years and 95.1% were females. Median duration of illness was 5 years (IQR: 3–9). Mean baseline FVC was 81.71%±9.35%, DLCO was 50.36%±14.24%, MDI was 7.68±2.72, 6MWD was 423.61±61.64 m, MRSS was 17.07±8.36. Fifteen subjects in MMF arm and 19 in placebo arm completed 6 months study duration. Mean change in FVC was −1.79±7.32% in MMF arm and 1.34%±4.47% in placebo arm. Mean absolute difference in FVC change from baseline to 6 months between the two arms was 3.13% (95% CI, −1.02 to 7.28; p=0.131). In mITT analysis, 15 subjects improved/stabilised and 5 subjects worsened in MMF arm compared to 19 and 2 subjects respectively in placebo arm. SF36v2 scores showed significant improvement in both the groups. No significant difference was noted between the two groups in mean change in focal score of MDI (3.33 vs 2.79; p=0.638), DLCO (2.46% vs 2.31%; p=0.412), 6MWD (2.8 m vs 12.11 m; p=0.522) and FVC among subjects with Scl-70 positivity (−2.19% vs 1.51%; p=0.184). The MRSS decreased by a mean of 4.73 points in MMF arm compared to 1.53 points in placebo arm (p=0.042). MMF was well tolerated and rates of diarrhoea and infections were similar to that with placebo. Three subjects on MMF and 1 on placebo discontinued drugs. <h3>Conclusions</h3> In this small study, MMF for 6 months was not effective in stabilising the lung disease in early and mild SSc-ILD but was effective in controlling skin disease and was well tolerated. <h3>References</h3> [1] Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354:2655–66. [2] Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomized controlled, double blind, parallel group trial. Lancet Respir Med. 2016;4:708–19. <h3>Disclosure of Interest</h3> None declared