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Effect of mycophenolate mofetil (MMF) on systemic sclerosis-related interstitial lung disease with mildly impaired lung function: a double-blind, placebo-controlled, randomized trial

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Abstract

The efficacy and safety of mycophenolate mofetil (MMF) has been studied in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD) with moderate–severe impairment. There is no study on its use in patients with mildly impaired lung function. The objective of this study is to determine the efficacy and safety of MMF for treating mild SSc-ILD (forced vital capacity (FVC) ≥ 70% predicted). This was a double-blind, randomized, placebo-controlled pilot trial. The subjects with SSc-ILD with FVC ≥ 70% were randomized to receive either MMF (2 g/day) or placebo for 6 months. FVC, diffusing capacity of lungs for carbon monoxide (DLCO), modified Rodnan skin score (mRSS), Short Form-36 (SF36v2), Mahler’s Dyspnoea Index (MDI), and 6-min walk distance (6MWD) were recorded at baseline and at 6 months. Forty-one subjects were included in the study (MMF: 20, placebo: 21). FVC decreased by a median of 2.7% (range − 21 to 9) in MMF arm and increased by 1% (range − 6 to 10) in placebo arm (p = 0.131). SF36v2 scores improved in both the groups. Median change in MDI (3 vs 3), DLCO (1% vs 1.5%), and 6MWD (0 m vs 0 m) was similar between the study groups. MMF was effective in improving mRSS (− 5 vs − 1, p = 0.045) compared to placebo. Adverse events occurred with similar frequency in both the study groups. In this pilot study, MMF did not result in significant improvement in lung function in SSc-ILD with minimally impaired lung function, but was effective in reducing the skin tightness. Larger studies are needed to confirm these findings. This study was registered at ClinicalTrials.gov (NCT02896205).

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Acknowledgements

We would like to thank Ipca Laboratories Limited, Mumbai, India for supplying the study drugs, MMF and placebo free of cost. This study was investigator-initiated and none of the personnel from the drug company was involved in the design, performance, or data analysis of the study or writing or reviewing of the manuscript.

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No funding was received by any of the authors.

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Authors and Affiliations

  1. Department of Internal Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Sector 12, Chandigarh, 160012, India

    G. S. R. S. N. K. Naidu, Shefali Khanna Sharma, M. B. Adarsh, Varun Dhir & Sanjay Jain

  2. Department of Pulmonary Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Sahajal Dhooria

  3. Department of Radiodiagnosis and Imaging, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Anindita Sinha

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  1. G. S. R. S. N. K. Naidu
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Contributions

All authors contributed to the design of the study, interpretation of the data, manuscript preparation and critical revisions of the manuscript. All authors approved the final version submitted for publication and agree to be accountable for all aspects of the study. Conception and design of the study: GN, SKS, VD, AS and SD. Data collection: GS, AM and SJ. Statistical analysis and data interpretation: GN, SKS, AM, VD and SD. Manuscript preparation: GN, AM, VD and SD. Manuscript revision: GN, SKS, VD, AS, SD and SJ.

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Correspondence to Shefali Khanna Sharma.

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Conflict of interest

GSRSNK Naidu, Shefali Khanna Sharma, Adarsh MB, Varun Dhir, Anindita Sinha, Sahajal Dhooria and Sanjay Jain declare that they have no conflict of interest. All the authors declare that they have no relationship with the organization promoting MMF.

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A written informed consent was obtained from all the participants included in this study and no identifying information of any participant was included in this article.

Ethical statement

The study was approved by the Institute of Ethics Committee (Ref. No. NK/2612/DM/10772). All the procedures performed in this study were in accordance to the guidelines set up by the Declaration of Helsinki in 1964 and later amended in 2000.

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296_2019_4481_MOESM1_ESM.jpg

Fig. S1 Change in FVC from baseline to 6 months in individual subject in both the study groups. FVC: forced vital capacity; MMF: mycophenolate mofetil. (JPG 66 kb)

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Naidu, G.S.R.S.N.K., Sharma, S.K., Adarsh, M.B. et al. Effect of mycophenolate mofetil (MMF) on systemic sclerosis-related interstitial lung disease with mildly impaired lung function: a double-blind, placebo-controlled, randomized trial. Rheumatol Int 40, 207–216 (2020). https://doi.org/10.1007/s00296-019-04481-8

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