JAK inhibitors are effective in a subset of patients with juvenile dermatomyositis: a monocentric retrospective study

Abstract

Objective To evaluate the efficacy and safety of JAK inhibitors (JAKi) in juvenile dermatomyositis (JDM). Methods We conducted a single-center retrospective study of patients with JDM treated by JAKi with a follow-up of at least 6 months. Proportion of clinically inactive disease (CID) within six months of JAKi initiation was evaluated using PRINTO criteria and skin Disease Activity Score. Serum IFN-α concentration was measured by SIMOA assay. Results Nine refractory and one new-onset patients with JDM treated with ruxolitinib (n = 7) or baricitinib (n = 3) were included. The main indications for treatment were refractory muscle involvement (n = 8) and ulcerative skin disease (n = 2). CID was achieved in 5/10 patients (2/2 anti-MDA5, 3/4 anti-NXP2, 0/3 anti-TIF1γ positive patients) within six months of JAKi introduction. All responders could withdraw plasmatic exchange, immunoadsorption and other immunosuppressive drugs. The mean daily steroid dose decreased from 1.1 mg/Kg (range 0.35–2 mg/Kg/d) to 0.1 (range, 0–0.3, p= 0.008) in patients achieving CID, and was stopped in two. Serum IFN-α concentrations were elevated in all patients at the time of treatment initiation and normalized in both responder and non-responder. A muscle biopsy repeated in one patient 26 months after the initiation of JAKi, showed a complete restoration of muscle endomysial microvascular bed. Herpes zoster and skin abscesses developed in three and two patients, respectively. Conclusion JAKis resulted in a CID in a subset of new-onset or refractory patients with JDM and may dramatically reverse severe muscle vasculopathy. Overall tolerance was good except for a high rate of herpes zoster infection.

The efficacy of bariticinib in real-world patients with refractory or severe juvenile dermatomyositis:a monocentric retrospective study

“…Previous study showed JAK inhibitor can restore muscle strength, signi cance improvement was observed after short usage [14,27,28]. In our study, one patient with severe muscle weakness was improved markedly (CMAS 15 to 30) upon baricitinib at 4 weeks of treatment.…”

“…Voyer and his colleague reported a new-onset case with severe skin ulcerations got CR after 1.7 months of baricitinib initiation [14].Calci cation is a therapeutic challenge in JDM. Data was limited in the treatment of JAKi in calci cation, one paper displayed that only partially regressed was observed in a case who had JDM complicated with calci cation.…”

“…Janus kinase(JAK)-signal transducer and activator of transcription (STAT) pathway plays a key role in cytokine transduces signals, JAK inhibitors undergo competitive ATP binding to interfere and downregulate type I and II cytokine signaling ,including IFNs signal. Actually, JAK inhibitors, such as tofacitinib, ruxolitinib and baricitinib had been reported to be used in JDM patients [12][13][14][15][16][17][18][19][20],which has shown e cacy in skin lesions, muscle weakness and amyopathic dermatomyositis-associated interstitial lung disease [12].However, data on use of bairicitinib in JDM is limited [16],the e cacy and safety are still unclear. Here we reported a series of refractory and new-onset severe JDM patient who had received baricitinib to evaluate it e cacy and safety in a real-world setting.…”

Inflammatory myopathies in childhood

“…As for other interferonopathies, the precise role of IFN-I in the pathology for jDM, and whether it is driving or secondary to the disease progression has been amply discussed. Using Digital ELISA, it was shown that circulating INF α levels in jDM patients correlate with disease activity [23 , 36] and response to treatment [37] . Furthermore, PBMCs isolated from jDM patients display a spontaneous production of IFN α in culture [38] .…”

“…Overall tolerance was good except for a high rate of herpes zoster infection. No severe adverse events (SA) or death related to the use of JAKIs were reported [37] . Thus, JKAIs seem a promising new targeting treatment of jDM.…”