Background: Excessive and inappropriate production of pro-inflammatory cytokines such as interleukin (IL)-1, IL-6 or IL-18, is a pathogenic cornerstone in adult and childhood onset Still’s disease. Beyond therapies targeting IL-1 or IL-6, Janus kinases (JAK) inhibitors have been proposed for adult-onset Still’s disease (AOSD) patients refractory to or intolerant of treatment with biologicals. Recently, it has been suggested that JAK inhibitors might be efficient in refractory AOSD patients ¹ .

Objectives: To assess the efficacy and safety of JAK inhibitors in the treatment of refractory systemic juvenile idiopathic arthritis (sJIA) or AOSD.

Methods: This retrospective study was based on a national survey of the departments of rheumatology, paediatric rheumatology and internal medicine in all French hospitals from an online call of the “Club Rhumatismes et Inflammation” ( www.cri-net.com ). The data were collected using a standardized questionnaire, and analyzed at different time points (treatment initiation, M1, M3, M6 and end of the follow-up). The response to JAK inhibitors was categorized as: complete remission (resolution of all clinical and biologic signs), partial remission (clinical improvement with persistence of a few symptoms) or failure (lack of clinical or biological improvement).

Results: 6 patients (5 adults and 1 child) were recruited ( Table 1 ). Mean age at treatment start was 39.6 years for the AOSD patient and 6 years for the sJIA patient, and mean disease duration was 5.3 years. The clinical expression was predominantly systemic in 5 five patients and chronic articular in one. Response to corticosteroids, conventional synthetic or biological Disease Modifying Anti-Rheumatic Drugs had been considered inadequate in all patients. Baricitinib was used in 3 patients, ruxolitinib in 2, and tofacitinib in 1. Steroids were concurrently used in all patients, anakinra in one, methotrexate and anakinra in one. At a mean (SD) follow-up of 9.5 months, partial response was observed in 4 (66.7%) cases (patients with ruxolitinib, tofacitinib or baricitinib) and failure in 2 (33.3%) (patients with baricitinib). No patient achieved complete remission. At the last visit, steroids could be decreased but not stopped in all patients. Patients with partial response had an average decrease of 72,8% (90% for tofacitinib, 70% for baricitinib, 58.5% for ruxolitinib between the start and the follow-up end date) and non-responder patients were yet able to reduce steroids by 60,5% ( Table 1 ). Tolerance of JAK inhibitors was excellent, however patient 4 experienced an episode of infectious pulmonary disease.

Conclusion: JAK inhibitors therapy may be helpful for some patients with refractory Still’s disease. However, no complete response was observed in this short series of cases. There might be a difference of response between the molecules, although the number of patients is too low to draw conclusions. Additional information is thus needed to evaluate more precisely the risk-benefit ratio of this treatment, and a possible difference in efficacy among the different groups of JAK inhibitors.

REFERENCES:

[1]Hu Q, Wang M, Jia J, et al. Ann Rheum Dis 2020;0:1–3. doi:10.1136/annrheumdis-2019-216

Acknowledgements: I thank all the coauthors, particularly Stéphane Mitrovic and Bruno Fautrel. Also, a special thank to the CRI.

Disclosure of Interests: None declared