Effectiveness and safety of mycophenolate mofetil in connective tissue disorder associated interstitial lung disease: A real-life experience from India

Authors

  • Sham Santhanam Glenegales Global Health City, Chennai
  • Vijil Rahulan Department of Pulmonology, Glenegales Global Health City.
  • Apar Jindal Department of Pulmonology, Glenegales Global Health City.

DOI:

https://doi.org/10.15305/ijrci/v9i1/345

Keywords:

Mycophenolate mofetil (MMF), connective tissue disorder, interstitial lung disease, CTD – ILD, efficacy, safety.

Abstract

Aim: To study the effectiveness and safety of mycophenolate mofetil (MMF) in patients with connective tissue disease (CTD) associated interstitial lung disease (ILD).

Methods: The retrospective observational study was carried out from Jan 2015 to Feb 2019. Symptomatic CTD-LD patients with (HRCT chest) documented ILD and abnormal pulmonary function test (forced vital capacity, FVC< 70%), who were treated with MMF were included. The treatment response was assessed clinically by pulmonary function test and radiology. Clinical assessment and PFT were done at baseline, 6, 12 and 24 months. HRCT chest was done at baseline and 24 months.

Results and analysis: Out of 33 patients, 13 had MCTD, 12 had RA, and remaining 8 belonged to the systemic sclerosis (SSc)-predominant groups (3: diffuse cutaneous SSc, 2: SSc/myositis overlap, and 1 each with Sjogren’s syndrome, SLE/Sjogren’s overlap and interstitial pneumonia with autoimmune features). Increased female predominance was noted (90.9%). The mean FVC at baseline noted in MCTD, RA and SSc-predominant groups were 62±6.17, 64±4.17 and 59±6 respectively. Improvement was reported in 4 patients, each in MCTD and RA groups. Eight patients in the MCTD group and 7 each in RA and SSc- predominant groups had a stable lung disease. One patient each in all the groups reported worsening of the disease. There was a positive trend in FEV1 and FVC with treatment. No significant difference in FEV1 and FVC values with treatment was noted across the three groups. Numerical differences in the mean values of FEV1 and FVC between two groups (NSIP and UIP) were noted, but was not statistically significant. All the subjects completed 24 months of follow-up. They were on 2 g/day of MMF for the first 12 months, followed by a maintenance of 1.5- 2 g/day for the next 12 months. None of the subjects discontinued treatment due to intolerance or adverse effects.

Conclusion:MMF was safe, effective and well tolerated. Treatment with MMF over 24 months stabilized the ILD in majority, improved in certain cases and rarely worsened.

References

Doyle TJ, Dellaripa PF. Lung Manifestations in the Rheumatic Diseases. Chest. 2017 Dec;152(6):1283-95.

Chan, C., Ryerson, C.J., Dunne, J.V. Wilcox PJ. Demographic and clinical predictors of progression and mortality in connective tissue disease-associated interstitial lung disease: a retrospective cohort study. BMC Pulm Med 19, 192 (2019).

Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, et al ; Sclerodema Lung Study II Investigators. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016 Sep;4(9):708-719.

Swigris JJ, Olson AL, Fischer A, Lynch DA, Cosgrove GP, Frankel SK et al. Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest. 2006;130(1):30–36.

Fischer A, Brown KK, Du Bois RM, Frankel SK, Cosgrove GP, Fernandez-Perez ER, et al. Mycophenolate mofetil improves lung function in connective tissue disease-associated interstitial lung disease. J Rheumatol. 2013 May;40(5):640-6.

Shenoy PD, Bavaliya M, Sashidharan S, Nalianda K, Sreenath S. Cyclophosphamide versus mycophenolate mofetil in scleroderma interstitial lung disease (SSc-ILD) as induction therapy: a single-centre, retrospective analysis. Arthritis Res Ther. 2016 Jun 2;18(1):123.

Naidu GSRSNK, Sharma SK, Adarsh MB, Dhir V, Sinha A, Dhooria S, Jain S. 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. 2020 Feb;40(2):207-216.

Acharya N, Sharma SK, Mishra D, Dhooria S, Dhir V, Jain S. Efficacy and safety of pirfenidone in systemic sclerosis-related interstitial lung disease-a randomised controlled trial. Rheumatol Int. 2020 May;40(5):703-710.

Singh P, Thakur B, Mohapatra AK, Padhan P. Clinical features and outcome of acute exacerbation in connective tissue disease-associated interstitial lung disease: A single-centre study from India. Int J Rheum Dis. 2019 Sep;22(9):1741-1745.

Tzouvelekis A, Galanopoulos N, Bouros E, Zacharis G, Ntolios P, Koulelidis A et al., “Effect and Safety of Mycophenolate Mofetil or Sodium in Systemic Sclerosis-Associated Interstitial Lung Disease: A Meta-Analysis,” Pulmonary Medicine, vol. 2012, Article ID 143637, 7 pages, 2012.

Lee WI, Hissaria P. Drug-Induced Inters al Lung Disease. Indian J Rheumatol 2019;14, Suppl S1:19-26.

Kiely P, Busby AD, Nikiphorou E, Sullivan K, Walsh DA, Creamer P, et al. Is incident rheumatoid arthritis inters al lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts. BMJ Open 2019;9:e028466.

Conway R, Low C, Coughlan RJ, O’Donnell MJ, Carey JJ. Methotrexate and lung disease in rheumatoid arthritis: A meta-analysis of randomized controlled trials. Arthritis Rheumatol 2014;66:803-12.

Singh S, Collins BF, Sharma BB, Joshi JM, Talwar D, Katiyar S et al. Interstitial Lung Disease in India. Results of a Prospective Registry. Am J Respir Crit Care Med. 2017;195(6):801–813.

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Published

08-03-2021

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