Abstract

BackgroundJAKi represent a new important class in Rheumatoid Arthritis (RA) treatment options. It is unknown which specific bDMARD or mode of action should be selected after stopping a JAKi.ObjectivesTo study if clinical response differs between advanced therapies that are initiated after stopping a JAKi.MethodsPatients were included from the electronic platform “Tool for Administrative Reimbursement Drug Information Sharing” (TARDIS). Data from all Belgian RA patients on biologic and targeted therapy are collected here for drug reimbursement. Patients were selected for this analysis if they had stopped JAKi therapy and initiated a subsequent therapy. Patients were grouped by TNFi, T/B cell therapy, IL6i or JAKi therapy. The DAS28 response and proportion of patients in remission at the first follow-up (between 3 and 6 months) were compared between groups. Remission was defined as DAS28<2.6. Analyses were repeated in patients who were prescribed the stopped JAKi as first-line or as subsequent line therapy. Data were compared via χ2, Anova and t-tests.ResultsIn total, 1238 patients who had stopped JAKi therapy were included. TNFi, T/B cell therapy, IL6i or JAKi therapy was initiated in 36% (441/1238), 19% (233/1238), 18% (227/1238) and 27% (337/1238) respectively. Most baseline demographic and clinical characteristics differed between groups (Table 1).Table 1.TNFiB/T cellIL6iJAKip-valueNumber441 (36%)233 (19%)227 (18%)337 (27%)Age (years)55 ± 1457 ± 1355 ± 1459 ± 12<0.001Gender (women)323 (73%)177 (76%)186 (82%)257 (76%)0.100Weight (kg)74 ± 1579 ± 1775 ± 1575 ± 150.111Disease duration (years)9 ± 810 ± 911 ± 911 ± 90.002HAQ (0-3)1.6 ± 0.71.8 ± 0.61.5 ± 0.71.5 ± 0.80.353PGA (0-100)65 ± 2068 ± 2167 ± 2157 ± 24<0.001CRP (mg/l)10 ± 1614 ± 2016 ± 2811 ± 170.003ESR (mm/h)22 ± 2124 ± 1927 ± 2125 ± 220.117TJC288 ± 68 ± 69 ± 67 ± 60.001SJC285 ± 46 ± 56 ± 45 ± 50.006DAS284.7 ± 1.14.8 ± 1.14.9 ± 1.24.4 ± 1.3<0.0012nd line of therapy after initial JAKi therapy211 (48%)56 (24%)52 (23%)112 (33%)<0.001Numbers given are mean ± SD or number, proportion. TNFi = tumour necrosis factor inhibitor, ts= targeted synthetic, HAQ= health assessment questionnaire, PGA= Patient Global assessment; CRP= C-reactive protein; ESR= erythrocyte sedimentation rate; TJC= tender joint count; SJC= Swollen joint Count; DAS28 = disease activity score based on the 28jointsThe clinical response could be studied in 577 patients. Patients on rituximab were excluded as these were retreated on flare, following Belgian reimbursement criteria. TNFi, Tcell therapy, IL6i or JAKi therapy was initiated in 37% (211/577), 13% (76/577), 18% (102/577) and 33% (188/577) of these patients respectively. DAS28 decreased on average with 1.7 ± 1.5, 1.6 ± 1.4, 2.4 ± 1.6* and 1.3 ± 1.6 for patients on TNFi, T cell therapy, IL6i or JAKi therapy respectively (*p<0.001). Remission was reached in 42%, 41%, 56%* and 39% for patients on TNFi, T cell therapy, IL6i or JAKi therapy respectively (*p=0.045).Before switching, JAKi therapy was the first advanced therapy in 35% (204/577). In this “naïve” subgroup, DAS28 decreased on average with 1.9 ± 1.5, 1.9 ± 1.3, 2.4 ± 1.8 and 1.0 ± 1.7* for patients on TNFi, Tcell therapy, IL6i or JAKi therapy respectively (*p=0.001). Remission was reached in 44%, 48%, 58% and 35% for patients on TNFi, Tcell therapy, IL6i or JAKi therapy respectively (p=0.279).In the “experienced” subgroup, who started JAKi therapy as subsequent line therapy in 65% (373/577), DAS28 decreased on average with 1.5 ± 1.6, 1.5 ± 1.4, 2.3 ± 1.6* and 1.4 ± 1.6 for patients on TNFi, Tcell therapy, IL6i or JAKi therapy respectively (*p<0.001). Remission was reached in 40%, 38%, 55% and 41% for patients on TNFi, Tcell therapy, IL6i or JAKi therapy respectively (p=0.118).ConclusionOur results show clearly that IL6 inhibitors have a better clinical response after JAKi cessation compared to other mode of actions, including other JAKi. However, considerable baseline differences existed, that could influence our results.Disclosure of InterestsNone declared

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