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Mycophenolate in idiopathic inflammatory myositis: outcome data of a large South Asian cohort

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Abstract

Background

Consensus on treatment of idiopathic inflammatory myositis (IIM), particularly with regard to flares and interstitial lung disease (ILD), does not exist. We studied the long-term outcome and treatment response in our large, retrospective cohort of adult South-Asian patients exclusively with IIM.

Methodology

Electronic records of IIM patients satisfying inclusion and exclusion criteria were studied longitudinally at presentation, at 3, 6, 12, 18 and 24 months and thereafter yearly till their last follow up (F/u) visit. Depending on clinical, imaging, and muscle enzyme profile during the F/u period, patients were categorised as complete (CR) and partial responders (PRs). Parameters favouring CR were assessed using multivariate logistic regression analysis. Outcome parameters and flares on immunosuppressants (IS) were then assessed in patients with/without ILD.

Results

Two hundred thirty-two patients with median F/u duration of 44.5 months (25–80.25) were included. ILD was seen in 40.1%. Patients with non-Jo1 anti-synthetase antibodies (n=26) were numerically more than those with Jo-1 antibody (n=24). CR status was attained by 50.9% patients. Absence of pericardial effusion (p=0.042, OR 4.223, 95% CI: 1.05–16.9) and presence of Gottron’s rash (p=0.044, OR 1.78, 95% CI 1.017–3.121) at baseline predicted CR by multivariate regression. Majority received mycophenolate during the entire F/u period. Discontinuation of steroids was feasible in 51.7% after a median duration of 24 months (18–42). After excluding patients with ILD, flares were numerically lesser in patients only on mycophenolate compared with those only on methotrexate (p=0.06). Further flares were curtailed when switched from other agents to mycophenolate.

Conclusion

Mycophenolate is an effective treatment option in IIM patients with and without co-existing ILD. Presence of Gottron’s rash and absence of pericardial effusion were found to be predictors of favourable clinical outcome in this largest single-centre study.

Key points

• This largest single-centre study of South Asian adult patients with idiopathic inflammatory myositis showed good clinical outcome and survival with combination treatment regimen consisting of upfront immunosuppressant especially mycophenolate mofetil or sodium (MMF/MMS) along with tapering doses of steroids.

• Absence of pericardial involvement and presence of Gottron’s rash were predictors of complete responders in our overall patient cohort.

• Testing anti-Jo-1 antibody alone during evaluation of myositis will overlook important prognostic biomarkers such as the presence of non-Jo 1 antisynthetase autoantibodies (PL-7, PL-12, EJ and OJ) as well as Ro52; our cohort had more patients with non-Jo 1 antibodies than Jo-1 antibody; hence, there is a strong case for testing the entire spectrum of myositis autoantibodies in IIM.

• Patients on MMF/MMS therapy from onset or even those switched to mycophenolate later had a better outcome, irrespective of their interstitial lung disease status.

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Data availability

Study data will be made available on request.

Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

AZA:

Azathioprine

BL:

Baseline

CADM:

Clinically amyopathic dermatomyositis

CPK:

Creatinine phosphokinase

CR:

Complete responders

CTD:

Connective tissue disease

CYC:

Cyclophosphamide

CYSP:

Cyclosporine

DM:

Dermatomyositis

F/u:

Follow up

IIM:

Idiopathic inflammatory myositis

ILD:

Interstitial Lung Disease

IS:

Immunosuppressant

JM:

Juvenile myositis

LDH:

Lactate dehydrogenase

MMF/MMS:

Mycophenolate mofetil/mycophenolate sodium

MMT8:

Manual Muscle Testing 8

MTX:

Methotrexate

PM:

Polymyositis

PR:

Partial responders

TAC:

Tacrolimus

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Acknowledgements

Dr. Janani for her help in this study.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Clinical Immunology and Rheumatology, Christian Medical College and Hospital (CMCH), Vellore, Tamil Nadu, 632002, India

    Aswin M. Nair, John Mathew, Ruchika Goel, Pramod Chebbi, Ashish Jacob Mathew, G. Arvind & Debashish Danda

  2. Department of Bio-statistics, CMCH, Vellore, Tamil Nadu, 632002, India

    Bijesh Yadav & Grace Rebekah

  3. Department of Microbiology, CMCH, Vellore, Tamil Nadu, 632002, India

    John A. J. Prakash

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  1. Aswin M. Nair
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Contributions

Dr. Aswin M Nair and Dr. Debashish Danda contributed to the study conception and design, material preparation, and data collection. Data analysis was performed by Bijesh Yadav, Grace Rebecah, Dr Aswin M Nair and Dr Debashish Danda. The first draft of the manuscript was written by Dr. Aswin M Nair, and all the authors commented on previous versions of the manuscript. Dr John Mathew assisted Dr Aswin M Nair in facilitation of data collection, and initial draft preparation. Dr Debashish Danda assisted Dr Aswin Nair in critical thinking, ongoing revision of the manuscript and addressing all reviewers' comments. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Debashish Danda.

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The institutional ethics committee approval was obtained. IRB Min No.13239.

Part of this manuscript has been published as an abstract in the EULAR 2020 proceeding Nair A, Goel R, Chebbi P et al. AB0596 Predictors, long term clinical and treatment outcomes in south Asian patients with idiopathic inflammatory myositis: a single center study. Annals of the Rheumatic Diseases 2020;79:1594-1595

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Nair, A.M., Mathew, J., Goel, R. et al. Mycophenolate in idiopathic inflammatory myositis: outcome data of a large South Asian cohort. Clin Rheumatol 40, 2805–2819 (2021). https://doi.org/10.1007/s10067-021-05590-1

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