BackgroundWith the availability of multiple Jak inhibitors (JAKi) for treatment, patients with RA who have had inadequate response to conventional therapies, including biologics, can now achieve favorable outcomes such as remission and low disease activity.However, it is also true that no single JAKi therapy is effective for all RA.Some RA treatment guidelines recommend a switch strategy from current JAKi to other JAKi or biologics in patients with inadequate response to JAKi therapy [1].There

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... s insufficient evidence to support the efficacy of switching to another JAKi in patients with inadequate JAKi response (JAKi-IR).ObjectivesThe aim of this study is to clarify the effectiveness of the strategy of controlling disease activity by switching to other JAKi in RA cases with JAKi-IR and to analyze the effect on serum cytokines related to the pathogenesis of RA.MethodsRA patients who switched to other JAKi during treatment with JAKi between September 2017 and January 2022 were included in this retrospective study.The clinical characteristics of the included RA patients were collected from their medical records.The efficacy of the JAKi switch strategy was assessed by changes in composite measure scores of disease activity, including DAS28-CRP, SDAI, and CDAI, at 4 and 12 weeks after the switch.In addition, changes of serum cytokines associated with RA pathogenesis (IL-6, TNF-α) were measured and analyzed by ELISA (Simple Plex, Protein Simple).ResultsTwenty-nine RA patients who received the JAKi switch treatment strategy were included in the analysis. The clinical characteristics of the included patients are shown in Table 1. All patients were receiving JAKi due to inadequate response to biologics. JAKi were switched to control disease activity including 3 cases (10%) who achieved temporary remission.Table 1.Baseline characteristics of the 29 patients enrolled this studyClinical characteristicsn=29Age57 [48.0-66.0]Sex (F/M)22/7 (75.9)Disease duration, years13 [8.6-18.8]RF positive26 (89.7)ACPA positive, (n=22)20(90.0)Concomitant medicationsMethotrexate, dose(mg/week)10 (34.5), 8.0 [6.0-10.5]Corticosteroid, dose(mg/day)17 (59.0), 4.0 [2.0-5.0]Disease activity DAS28-CRP3.77 [3.2-4.6] SDAI15.5 [9.8-21.1] CDAI14.5 [9.5-20.0]Patient global assessment of disease activity (mm)40 [25-58]Provider global assessment of disease activity (mm)32 [15-40]CRP (mg/dl)0.9 [0.1-1.7]TJC/SJC4 [2-5], 2[2-5]Date are n (%) or median [IQR].Figure 1 shows the effect of the JAKi switch strategy on the disease activity category.Evaluation using SDAI showed that 65% of patients achieved the immediate treatment goal of low disease activity at 4 weeks after switch, and 69% of patients maintained this goal at 12 weeks. SDAI remission was also observed in 17% of patients at 4 weeks and 31% at 12 weeks, demonstrating the efficacy of the JAKi switch strategy. The efficacy of the JAKi switch strategy was also observed in other measures of disease activity.Changes in serum cytokines (IL-6, TNF-α) associated with disease activity in RA before and after JAKi switch were analyzed in 10 patients. Regardless of the type of JAKi, serum IL-6 was decreased by JAKi switch in most cases at 12weeks (average change of serum IL-6: -27.25pg/ml).However, no trend was observed for changes in serum TNF- disease acti(average change of serum TNF-ed for change).There was no clear association between changes in these two cytokines and the efficacy of the JAKi switch strategy.ConclusionThe composite disease activity index showed that about 60% of JAKi-IR patients achieved low disease activity, one of the treatment goals, at 4 weeks after switching to JAKi, and the effect was maintained up to 12 weeks. This effect did not appear to be related to the type of JAKi.The effects of biologic therapy on serum cytokines associated with RA activity differed from the effects of the JAKi switch strategy.References[1]György Nagy, et al. EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis. Annals of the Rheumatic Diseases 2022;81:20-33.Disclosure of InterestsNone declared