Successful treatment of extensive calcifications and acute pulmonary involvement in dermatomyositis with the Janus-Kinase inhibitor tofacitinib – A report of two cases

Abstract Introduction Dermatomyositis(DM) can be complicated by calcinosisand interstitial lung disease(ILD). Calcinosiscan be severely debilitating or life-threatening and to date there is no treatment with proven efficacy. In DM type I interferon contributes to pathophysiology by inducing the expression of proinflammatory cytokines and the JAK-STAT (signal transducer and activator of transcription) pathway may be involved in the regulation of mitochondrial calcium store release, a process potentially important for calcificationin DM. JAK-inhibition may therefore be an attractive therapy in DM complicated by calcifications. Methods and results We report on the fast and persistent response of extensive and rapidly progressive DM-associated calcificationsin two patients treated with the JAK-inhibitor tofacitinib. During the 28-week observation period in both patients no new calcificationsformed and existing calcificationswere either regressive or stable. Furthermore, concomitant life-threatening DM-associated ILD (acute fibrinous and organizing pneumonia; AFOP) in one patient rapidly responded to tofacitinibmonotherapy. Both patients were able to taper concomitant glucocorticoids. Tofacitinibwas well tolerated and safe. Conclusions The results of our study support the role of JAK/STAT signaling in the development of calcinosisand ILD in DM. Tofacitinibmay be an effective and safe treatment for calcinosisin DM and potentially for other connective tissue diseasecomplicated by calcinosis.