Background:Small-molecule JAK inhibitors have succeeded in the treatment of rheumatoid arthritis, psoriasis, and inflammatory bowel disease1. Tofacitinib is under investigation for various autoimmune diseases2, but its effectiveness on Behçet’s disease(BD) has not been demonstrated.Objectives:We aimed to investigate the efficacy and safety of Tofacitinib in the treatment of severe and refractory BD.Methods:We retrospectively analyzed the efficacy and safety profile of Tofacitinib in treating severe and refractory BD patients in our hospital from 2017 to 2020.Results:Thirteen BD patients (7 males and 6 females) were enrolled, with a mean age and median course of 40.6±14.7 years and 84 months (60, 132). Vascular/cardiac, gastrointestinal, and articular involvement were presented in 5, 6, and 2 patients, respectively. Three patients had multiple arterial stenosis or occlusion, two presented with aortic root dilation with aortic valve regurgitation, and one experienced perivalvular leakage (PVL). All the six patients with gastrointestinal involvement had multiple episodes of ileocecal and colon ulcers, intestinal bleed, and three had anastomotic ulcers or leaks.All the patients had received high-dose glucocorticoids and immunosuppressants before tofacitinib therapy, they displayed poor response with evidence of disease progression; furthermore, three patients with gastrointestinal involvement and one patient with polyarthritis had failed anti-TNF antibody treatment. They were then treated with Tofacitinib, 5mg twice daily, with background glucocorticoids and immunosuppressants, for a median of 6 months (range 4 to 19).After a median follow-up of 7 (5, 19) months, the ESR and CRP level decreased significantly (21(8, 50) mm/h vs 8(3, 19.5) mm/h, P<0.01, and 25(5.85, 49.5) mg/L vs 1.89(0.44, 6.65) mg/L, P<0.01, respectively). All patients with vascular/cardiac and articular involvement achieved clinical improvement. Vascular lesions of three patients were radiologically stable, no progressive aneurysm or PVL was observed. Two patients with intestinal ulcers revealed complete mucosal healing; the other three had sustained elevation of ESR and CRP, active mucosal ulcers, recurrent bleeding, or fistula formation. The dose of corticosteroids was tapered in six cases (46.2%), furthermore, the number of immunosuppressants lessened in seven cases. However, two patients had herpes zoster infection during follow up, while being treated with five to six immunosuppressants in addition to Tofacitinib for refractory intestinal ulcers.Conclusion:Our study suggests that Tofacitinib is effective for the treatment of vascular and articular BD; given the limited data, its therapeutic effect on gastrointestinal BD could not be validated. We have to be cautious of infectious risk for severely immunocompromised patients. Further large-scale prospective studies are warranted to confirm the therapeutic potential of JAK inhibitors in BD patients.References:[1]Banerjee, S., Biehl, A., Gadina, M., Hasni, S. & Schwartz, D. M. JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects. Drugs 77, 521–546 (2017).[2]Fragoulis, G. E., Mcinnes, I. B. & Siebert, S. JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis. Rheumatol. (United Kingdom) 58, i43–i54 (2019).Disclosure of Interests:None declared
Janus Kinases in Leukemia
