Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by chronic
inflammation in the skin and muscle. Anti-melanoma differentiation-associated gene5
(Anti-MDA5) antibody positive DM is a subtype of DM that is more frequent in East Asia, which
is often exhibit skin lesion, clinically amyopathic and interstitial lung disease. About
42%-100% of patients with Anti-MDA5+ DM develop rapidly progressive interstitial lung disease
(RPILD) and result in respiratory failure. The mortality is as high as 40% within 6 months.
In addition, not every patient with Anti-MDA5+ DM respond to traditional treatment strategy
and most of the patients are resistant to immunosuppressive therapy including a combination
of high dose glucocorticoids(GCs) and immunosuppressants such as cyclosporine, tacrolimus, or
cyclophosphamide. However, RP-ILD is still the main cause of death due to fatal respiratory
failure. Therefore, treatment of Anti-MDA5+ DM patients is challenging.The excessive
production of multiple cytokines plays a crucial role in the development of Anti-MDA5+ DM
patients complicated with ILD. Hyperferritinemia is a predictor of poor prognosis. Other
abnormalities included lymphopenia, increased erythrocyte sedimentation rate(ESR), and
elevated serum interleukin-18 (IL-18).Moreover, compared with Anti-MDA5- DM patients, serum
interferon--α(IFN-α) concentration increased in Anti-MDA5+ DM patients with RP-ILD.
Therefore, blocking multiple cytokines may become a new target for the treatment of this
disease.Jakinibs is a Janus kinase (JAK) inhibitor that blocks a variety of cytokines, such
as type I and type II IFN. Few studies have reported a positive response to JAK inhibitor for
Anti-MDA5+ DM. Kazuhiro et al. reported in 2018 that JAK inhibitor tofacitinib may be an
effective treatment option for high risk amyopathic dermatomyositis (ADM) -ILD patients after
failure of conventional treatment, but the number of cases is too small. And a recent paper
showed that great efficacy of tofacitinib for the improvement of survival of
anti-MDA5-positive early-stage ADM-ILD patients.The aim of this study is to evaluate the
efficacy and safety of JAK inhibitors in the treatment of anti-MDA5+ DM patients, and to
evaluate the effect of JAK inhibitors on B cells of these patients, so as to provide a new
target and theoretical basis for the treatment of anti-MDA5+ DM.This was a single-arm
open-label pilot observational study. Patients were received a glucocorticoids
(0.8mg-1mg/kg/day) and a combination with tofacitinib (at a dose of 5 mg twice daily).
Inactive disease was defined as meeting the following three criteria: CK≤200U/L, physician
visual analogue scale(VAS) =0, and myositis disease activity assessment visual analog scales
(MYOACT) scores =0. Otherwise, the disease condition was considered to be active.The primary
endpoint was the number of responders by total improvement score (TIS) ,which defined
according to 2016 American College of Rheumatology(ACR)-European League Against
Rheumatism(EULAR) Criteria for clinical response for adult DM/polymyositis(PM), after
treatment with tofacitinib for 12 months. A TIS (0-100), determined by summing scores in each
International Myositis Assessment and Clinical Studies Group (IMACS) core set measures (CSM).
Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the
TIS. Secondary endpoints included safety measures and change from baseline in the following
index: percentage of predicted FVC (FVC % predicted) and percentage of predicted DLCO (DLCO%
predicted), the ferritin level, peripheral lymphocyte subsets.