AB0405 JAK INHIBITORS IMPROVE PATIENT-REPORTED OUTCOMES SUCH AS PAIN AND HAQ EARLIER THAN ANTI-IL-6 INHIBITORS

Abstract

BackgroundClinical feature of Janus kinase (JAK) inhibitor is recognized as not only suppress inflammation but also improve patient-reported outcomes (PRO) such as pain and health assessment questioner (HAQ) in patients with rheumatoid arthritis (RA). This representative clinical feature was known as a results of phase 3 trial compared to TNF inhibitor. One of the mechanisms of JAK in RA is to suppresses interleikin-6 (IL-6). However, the effect for PRO in JAK inhibitor compared to IL-6 inhibitor have not been known.ObjectivesWe investigated the effect for patient-reported outcomes such as pain and HAQ in patients with RA treated with JAK inhibitor compared to IL-6 inhibitor.MethodsThis study was analysed a multicenter database included RA patients treated with biological disease-modifying anti rheumatic dugs (bDMARDs) and JAK inhibitors. In 307 patients treated with IL-6 inhibitor (tocilizumab 240 and sarilumab 67) and 220 patients with JAK inhibitor (tofacitinib 101, baricitinib 83, upadacitinib 20, peficitinib 14 and filgotinib 2), 155 patients were treated as first-line bDMARDs/JAK inhibitor (IL-6R inhibitor 104 and JAK inhibitor 51). In this first-line patients, patients treated with IL-6R inhibitor and JAK inhibitor were matched using the propensity score adjusted for gender, age, RA disease duration, baseline charactristics of disease activity, CRP level, and MMP-3 level. The beaseline data and the change of clinical and laboratory data at 4, 12 and 24 weeks were compared between IL-6 inhibitor and JAK inhibitor.ResultsThirty-six patients in each group were matched and analyzed. The average age was 62.4 and 62.6 years and the average disease duration of RA was 13.2 and 10.1 years in IL-6 inhibitor and JAK inhibitor. The baseline characteristics were not significantly different in both groups. At week 4, tender joint count (TJC) was significantly improved in JAK inhibitor than IL-6 (IL-6: -1.86 vs JAK: -4.12, p= 0.036) and HAQ was significantly improved in JAK inhibitor than IL-6 (IL-6: -0.04 vs JAK: -0.27, p= 0.041). Moreover, Clinical Disease Activity Index (CDAI) was also improved in JAK inhibitor than IL-6 (IL-6: -6.6 vs JAK: -10.9, p= 0.026) at week 4. However, pain VAS and patient global VAS were not significantly different in each group in week4. TJC, HAQ and CDAI was not different in both groups at week 12 and week 24. On the other hand, ESR was significantly decreased in IL-6 inhibitor than JAK inhibitor at week 4, 12 and 24 (IL-6: -26.6 vs JAK: -14.1, p=0.018 at week 4, IL-6: -32.7 vs JAK: -16.5 p=0.004 at week 12, IL-6: -31.3vs JAK: -17.7 p=0.014 at week 24).ConclusionIn a comparison between IL-6 inhibitor and JAK inhibitor as a first-line molecular-targeted drug matched baseline charactristics of disease activity, TJC and HAQ was improved in JAK inhibitor earlier than IL-6 inhibitors. JAK inhibitor suppress multi cytokine that might be the reason why JAK inhibitor improve pain. Improvement of patient reported outcome in JAK inhibitor was found also in comparison with IL-6 inhibitor.