Original article Management of refractory cutaneous dermatomyositis: potential role of Janus kinase inhibition with tofacitinib Siamak Moghadam-Kia 1,2 , Devon Charlton 1 , Rohit Aggarwal 1 and Chester V. Oddis 1 Abstract Objectives. Some patients with cutaneous DM demonstrate incomplete responses to conventional ther- apy while some, including those with extra-cutaneous manifestations, experience disease recurrences. Janus kinase/signal transducers and activators of transcription pathway inhibition has been reported to mitigate IFN signalling, which is thought to contribute to disease pathogenesis in DM. Four cases of refractory DM responsive to tofacitinib have been reported in the literature. Our case series investigated the use of tofacitinib in refractory cutaneous DM. Methods. Our case series includes four subjects with refractory DM who received tofaticinib after failure of several immunosuppressive and immunomodulatory agents. Results. All four subjects responded well to tofacitinib with significant improvement in cutaneous and extra-cutaneous manifestations. Conclusion. Tofacitinib can improve cutaneous and inflammatory articular manifestations in refractory DM. Key words: dermatomyositis, treatment, tofacitinib Rheumatology key message . Tofacitinib can be efficacious for management of cutaneous manifestations and inflammatory arthropathy in refractory dermatomyositis. Introduction DM, a subset of idiopathic inflammatory myopathy, is a systemic autoimmune rheumatic disease with character- istic cutaneous manifestations. Traditional treatment approaches include glucocorticoids and conventional im- munosuppressive or immunomodulatory agents such as hydroxychloroquine, methotrexate, azathioprine, myco- phenolate mofetil, tacrolimus, ciclosporin, and IVIG. Some patients with DM fail to respond completely or have recurrences with these medications. Biomarkers related to type I IFN signalling including in- ducible transcripts and proteins are elevated in DM muscle and skin [14] and it has been postulated that lichenoid skin reactions and perifascicular atrophy in muscle may be directly related to type I IFN signalling. Further, Janus kinase (JAK)/signal transducers and acti- vators of transcription (STAT) pathway inhibition mitigates IFN signalling [5]. Four cases of refractory DM responsive to tofacitinib [6, 7] have been reported and ruxolitinib, a JAK inhibitor, was effective for the treatment of refractory DM in a 72-year-old woman with a concomitant JAK2 mutation-associated myeloproliferative neoplasm [8]. Tofacitinib has been used in other inflammatory skin con- ditions including moderate-to-severe plaque psoriasis, alopecia areata and vitiligo [9]. We report four cases of refractory DM responding to tofacitinib with significant im- provement in cutaneous and extra-cutaneous features. This study was approved by the University of Pittsburgh School of Medicine. 1 Myositis Center and Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine and 2 Department of Rheumatology, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA Correspondence to: Chester V. Oddis, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, S705 BST, 3500 Terrace Street, Pittsburgh, PA 15261, USA. E-mail: cvo5@pitt.edu Submitted 26 April 2018; accepted 22 August 2018 ! The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com RHEUMATOLOGY Rheumatology 2019;58:10111015 doi:10.1093/rheumatology/key366 Advance Access publication 3 January 2019 CLINICAL SCIENCE Downloaded from https://academic.oup.com/rheumatology/article/58/6/1011/5272713 by guest on 16 February 2023