AB0135 A VERY EARLY CLINICAL RESPONSE TO TOFACITINIB IS ASSOCIATED WITH LOW RHEUMATOID ARTHRITIS ACTIVITY AFTER 3 AND 6 MONTHS
Authors: A. Karateev, A. Lila, E. Nasonov, V. Mazurov, D. Chakieva, A. Dadalova, A. Dyo, A. Baranov, N. Lapkina, E. Koltsova, N. Kiryukhina, D. Murtazalieva, I. Shchendrigin, T. Rasevich, A. Davydova, I. Semizarova, I. Shafieva, I. Bashkova, D. Bobrikova, I. Kushnir, E. Kalinina, T. Salnikova, V. Sorotskaya, R. Samigullina, I. Marusenko, O. Semagina, I. Vinogradova, D. Kretchikova, M. Semchenkova
Journal: Annals of the Rheumatic Diseases (2021)

Background: JAK inhibitors block intracellular signaling pathways responsible for the synthesis of cytokines and mediators involved in the development of chronic pain and central sensitization (CS). This determines a very rapid clinical response to JAK inhibitors. However, it is not clear how the significant pain reduction in the first weeks of therapy is associated with the achievement of low rheumatoid arthritis (RA) activity. Objectives: to assess the relationship between the early clinical response to tofacitinib and the decrease in RA activity after 3 and 6 months. Methods: Study group included 88 patients with RA, their age was 53±11,5, 79.3% of women, 89.8% of RF “+”, DAS28 5.2±1.2, receiving DMARDs (methotrexate 59.5% and leflunomide 19.8%), who were administered with tofacitinib 5 mg 2 times a day due to inefficacy or intolerance of biological DMARDs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration, RA activity using DAS28 after 3 and 6 months. Results: The mean pain severity at baseline was 5.3±2.0 according to the visual analogue scale (VAS 0-10), 51.1% of patients had signs of central sensitization (CSI ≥ 40), 15.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.1±1.8 (р&lt;0.05) and CS – CSI from 40.4±13.5 to 36.5±12.5 (р=0.01). After 28 days, the effect was higher: the pain level (VAS) was 2.8±1.6 (p=0.000), PainDETECT decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CSI – to 31.6±13.9 (p=0.000). DAS28 after 3 and 6 months was 3.7±1.3 and 3.6±1.2. The number of patients with pain decrease of ≥50% after 28 days of therapy was 59.9%. Low RA activity after 3 months. (DAS28 ≤3.2) was achieved in 64.4% of patients. There was a clear correlation between the number of patients with significant pain reduction at 28 days and the number of patients with low RA activity after 3 and 6 months (r S =0.548, p=0.000; r S =0.790, p=0.000). Six patients withdrew from the study due to inefficacy or social reasons. There were no serious adverse reactions. Conclusion: The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect and reduce CS signs. An early clinical response to tofacitinib (pain relief) predicts a decrease in RA activity after 3 and 6 months of the therapy. Limitation: Open-label observatory study. Disclosure of Interests: None declared