There has been increasing evidence documenting the critical role of type I IFNs in the development of JDM. Baricitinib, a JAK1/JAK2 inhibitor, interfering with I IFNs expression or signaling have already shown favourable results with baricitinib in refractory or sever newly JDM[16, 17, 26].
In this study, patients with cutaneous manifestations were improved markedly after baricitinib therapy. Significant improvement was noted at week 4 in skin DAS(P=0.008). It was consistent with previous cases report that indicated baricitinib was clinically beneficial to skin lesions[16, 17, 26]. A case serials reported that 4 refractory JDM with baricitinib also showed skin disease improvement by week 4 [16]. Voyer and his colleague reported a new-onset case with severe skin ulcerations got CR after 1.7 months of baricitinib initiation [14]. Calcification is a therapeutic challenge in JDM. Data was limited in the treatment of JAKi in calcification, one paper displayed that only partially regressed was observed in a case who had JDM complicated with calcification[27, 28]. In our study, only partially regressed in one (1/3) patient with calcification in this study. Baricitinib may show good efficacy in the treatment of calcification if expanded the observation duration.
Previous study showed JAK inhibitor can restore muscle strength, significant improvement was observed after short usage[14, 29, 30]. In our study, one patient with severe muscle weakness was improved markedly (CMAS 15 to 30) upon baricitinib at 4 weeks of treatment. However, possible reason was that most patients enrolled in this study had mild muscle involvement.
JDM patients with ILD are often refractory to therapy. It was found that patients with anti-MDA5 antibodies positive were more prone to develop ILD[12, 28, 31–33][34, 35]. Four patients with ILD in our series had different MSAs (Table 1), an anti-PL-7-positive patient showed complete remission in images under the treatment of baricitinib. However, small size of our cohort makes it hard to distinguish which type of MSAs is an indication for the use of baricitinib.
It is reported that interference with IFN α/β expression or signaling following JAK/STAT inhibition may control catastrophic hyperinflammation in MAS[36, 37]. With comprehensive treatment that including IVMP, IVIG, tocilizumab and baricitinib, one patient effectively tackle the cytokine storm to get disease remission, which showed the possibility of baricitinib treatment of MAS in the real world.
Consistent with previous study, bariticinib maybe helpful for tapering the dose of steroid and other immunosuppressive medicine. In some case reports, JAK inhibitor may be beneficial when used alone[20]. In this study, daily corticosteroids were decreased from 0.632mg/kg/day at the entry of study, to 0.357mg/kg/day (P=0.043). Half of these patients were able to reduce or remove other immunosuppressive medications.
Due to high price and off-label drug use, patients received dose of baricitinib from 1mg to 4mg per day, which is lower than other studies[16, 38]. It was cost-effective to get response in 8/15 patients during 6 months usage in this study. While, the non- response or PR in many patients might be due to this under-dosing, that’s one of our limitations in this study.
Bariticinib was reported as well-tolerated and safe in previous study[16, 29]. In our study, the most common AE was mild respiratory infection (Table 3). One patient infected with herpes zoster had to temporarily suspended using of Bariticinib. BK virus infection was often occurred in patients who receive immunosppressants or renal transplantation, while due to the lack of detection method and the absence of clinical manifestations of kidney disease in our patients, we did not routinely detect this virus.
Our study has another limitation as a single-centre study with small sample size and short observation period. It was carried out in a routine clinical practice situation, the effects of basic and combined medications may influence the truly efficacy of bariticinib. In addition, we did not measure the concentration of interferon-α protein made it unable to assess changes of in interferon expression in a molecular level.