LAUSR

JAK inhibitors (JAKi) are relatively recently licenced for treatment of inflammatory arthritis. Therefore, long term data regarding outcomes for patients cycling through multiple JAKi are lacking. However, one recent international cohort study (Pombo Suarez et al) suggested cycling JAKi is similarly efficacious as switching to an alternative biologic DMARD after initial treatment failure. The aim of this study was to assess outcomes for patients switching JAKi in a large, UK teaching hospital. This was a retrospective cohort study of patients prescribed a JAKi for inflammatory arthritis at Sheffield Teaching Hospitals. Patients who had received two or more JAKi were identified through a local biologic database. Demographic data, antibody status, concomitant medications, previous biologics, and reasons for switching therapy were collected. We identified 20 patients who had cycled through JAKi. The diagnosis was Rheumatoid arthritis in 75% (n = 15) of patients. The remaining patients had Psoriatic arthritis (n = 3), seronegative inflammatory arthritis (n = 1) or axial spondyloarthritis (n = 1). 95% (n = 19) of patients were female. 50% of patients used concomitant DMARD therapy and 15% were prescribed concomitant steroids. 85% (n = 17) of patients had received two JAKi and 15% (n = 3) had received three. Initial JAKi prescribed was Baricitinib in 40%, Tofacitinib in 40%, Filgotinib in 10% and Upadacitinib in 10% of patients. The most frequent reason for cycling JAKi was secondary loss of efficacy, affecting 40% (n = 8) of patients. The duration of treatment before loss of effect ranged from 6-45 months (IQR 12-31 months). 100% of these patients remain on their second JAKi with good response. 35% (n = 7) of patients stopped initial JAKi therapy due to side effects. These included gastrointestinal upset, headaches, and rash. 86% (n = 6) of these patients did not tolerate a second JAKi due to re-occurrence of the same side effect, including one patient with recurrence of the same side effect on a third JAKi. One patient who had headaches with their first JAKi has remained well on their second JAKi. 20% (n = 4) of patients changed therapy due to primary nonresponse to initial JAKi. One patient failed to respond sufficiently to either JAKi and alternative treatment was commenced. Three patients responded to a second JAKi, although two later lost efficacy and are currently responding well to a third JAKi. One patient switched JAKi due to cardiovascular risk with Tofacitinib. This study supports recent studies in finding that cycling JAKi in patients who lose efficacy or do not respond to initial JAKi can be an effective treatment strategy. However, in patients who stop initial JAKi due to side effects, cycling to a further JAKi is less likely to be successful, with recurrence of side effects in most cases. Disclosure E.M. Quinlan: None. M. Cox: None. J.R. Maxwell: Honoraria; BMS, Pfizer, Abbvie, Lilly, Gilead.