Tofacitinib for recurrence of antimelanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis after remission

Abstract

Rationale: Antimelanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive clinically amyopathic dermatomyositis (cADM) is frequently complicated with interstitial lung disease (ILD) and has a poor prognosis. Although the short-term prognosis of anti-MDA5 Ab-positive cADM is poor, it has been suggested that the recurrence rate is not higher than that of anti-MDA5 Ab-negative dermatomyositis. Combination therapy with corticosteroids, calcineurin inhibitors, and cyclophosphamide is the gold standard for the remission induction therapy at the onset. Recently, it has been reported that tofacitinib (TOF) could be effective for refractory anti-MDA5 Ab-positive cADM with ILD. Although initial remission induction therapy has been established, therapeutic strategies for relapse cases have not yet been established. Patient concerns: A 57-year-old woman who was diagnosed with anti-MDA5 Ab-positive cADM complicated with ILD. In October 2016, she was treated with prednisolone (PSL), tacrolimus (TAC), and cyclophosphamide (CY). These treatments were successful, and PSL could be tapered. However, she developed strong nausea and general fatigue as adverse events of CY. In April 2018, PSL was discontinued, and maintenance therapy was given with TAC. In July 2018, Gottron's sign and ILD recurred. Skin lesions on the finger were partially ulcerated and ILD was also worsening. We proposed a remission reinduction therapy including CY. However, she was rejected CY from experience with past adverse event of CY. Diagnosis: Based on skin lesions and chest computed tomography (CT) findings, the diagnosis was a recurrence of anti-MDA5 Ab-positive cADM with ILD. Interventions: Treatment by TOF 10 mg and PSL 22.5 mg (0.5 mg/kg equivalent) was introduced in November 2018. Outcomes: After introducing TOF and PSL, her skin lesions and chest CT findings of ILD gradually improved. Six months after the induction of TOF, the skin ulcer was epithelialized. One year after the introduction of TOF, PSL was decreased to 9 mg, and the disease activity did not re-exacerbate. Lessons: This case report is the first report suggesting the effectiveness of TOF for recurrent case of anti-MDA5 Ab-positive cADM with ILD. TOF might be an effective therapeutic option for treating recurrent case of anti-MDA5 Ab-positive cADM.

Tofacitinib for the Treatment of Severe Interstitial Lung Disease Related to Rheumatoid Arthritis

“…About the possible effect on ILD, some case reports have recently been published in which tofacitinib appears to be effective on ILD related to antimelanoma differentiation-November 2017 associated 5 gene antibody-positive dermatomyositis and antisynthetase syndrome [20][21][22][23].…”

Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies

“…Some studies suggest that beyond 6 months after onset, disease progression tends to settle down, and relapse seems uncommon ( 10 ). However, recurrences have also been described in the form of cutaneous and/or severe respiratory relapse many years after onset and after months of clinical remission and new treatments are needed to contain the exacerbation ( 47 , 48 ).…”

“…Data regarding the improvement of cutaneous lesions after intensive IS treatment are scarce but some case reports of cutaneous lesions refractory to IS drugs have been published ( 48 , 137 , 176 ). As the vascular injury seems to have a central role in the development of skin lesions, drugs such as sildenafil, a vasodilatator, or bosentan, an endothelin-receptor inhibitor, might be added to the IS treatment to treat the skin ulcerations ( 32 , 133 – 135 ).…”

Management of Myositis-Associated Interstitial Lung Disease

“…Rapidly progressive DM-/CADM-ILD is characterized by the overproduction of multiple cytokines, especially in patients with anti-MDA5 antibodies [ 95 , 96 ]. Emerging data support the use of TOF in patients with DM-/CADM-ILD with anti-MDA5 antibodies [ 66 , 67 , 68 , 97 , 98 ]. Kurasawa et al retrospectively reviewed the efficacy of TOF (10 mg/day) for patients with anti-MDA5 antibody-positive DM-ILD who were resistant to triple therapy, including high-dose GCs, CsA, and CY [ 66 ].…”