Dermatomyositis is an inflammatory autoimmune disease that affects the skin and muscles, with vasculopathy. Like a genetic interferonopathy, it is accompanied by an overexpression of genes dependent on type 1 interferon, which activates the janus kinase signaling pathway – signal transducers and activators of transcription (JAK- STAT). In 2018, researchers from the Institute of Myology helped demonstrate in vitro and in vivo the benefit of a janus kinase inhibitor (ruxolinitib) in refractory dermatomyositis.
A growing number of arguments in favor of JAKi
This therapeutic avenue has since been the subject of several publications in small series and case reports. In November 2020, a Japanese team reported the success of another janus kinase inhibitor (JAKi), tofacitinib (Xeljanz®), in a man suffering from dermatomyositis with interstitial lung disease, refractory to triple immunosuppressive therapy.
A month later, a team from Johns Hopkins University (US) published the results of the STIR pilot study for Study of Tofacitinib In Refractory dermatomyositis. This single-center phase I clinical trial (essai clinique de phase I) included 10 adults aged 35 to 56 years with, for an average of 6.5 years, predominantly skin dermatomyositis. After a washout period of immunosuppressants and immunomodulators, 12 weeks of treatment with 11 mg / day of tofacitinib resulted in:
- a significant improvement according to the criteria of the IMACS (International Myositis Assessment and Clinical Studies Group) in 100% of the participants;
- this was the primary endpoint of the trial; a significant improvement in the CDASI (Cutaneous Dermatomyositis Disease Area and Severity Index) skin severity index in the 10 participants as well;
- a significant change in the serum concentration of chemokines 9 and 10 (CXCL 9/10) in all participants;
- a marked reduction in the STAT1 signal in 3 of 9 participants who had a skin biopsy.
For the authors, these results reflect the “strong clinical efficacy” of tofacitinib in refractory dermatomyositis, but randomized controlled clinical trials are needed. In the meantime, another JAKi, baricitinib, is expected to be evaluated soon in a phase II clinical trial (NCT04208464 ou MYOJAK) in the UK in 25 adults with refractory dermatomyositis.