Dynamics of clinical manifestations and cytokine levels in patients with rheumatoid arthritis associated with upadacitinib therapy

Abstract

BACKGROUND: Recently, it has become evident that despite extensive data obtained from randomised placebo-controlled trials, which are still the golden standard for assessing the efficacy and safety of therapy, there are still some fundamentally important questions regarding the optimal management of patients with rheumatoid arthritis. In this regard, it is extremely relevant to assess the results of therapy in real clinical practice. Currently, much attention is paid to the study of the level of proinflammatory cytokines, both as markers of inflammatory activity of rheumatoid arthritis and monitoring the prognosis of anti-inflammatory therapy efficacy. In Russia, there are no works devoted to the study of cytokine concentration dynamics in patients with rheumatoid arthritis on the background upadacitinib therapy, which proves the relevance of the following study.
 AIM: To investigate the dynamics of clinical and laboratory values of inflammatory activity of the disease and cytokines in patients with rheumatoid arthritis associated with upadacitinib therapy.
 MATERIALS AND METHODS: We examined 10 patients with a reliable diagnosis of rheumatoid arthritis: patients’ age was 46.30 ± 10.20 years and disease duration was 12.00 (3.00–21.00) years. All the patients had moderate to high disease activity: Disease Activity Score-28 with erythrocyte sedimentation rate 5.48 (4.50–5.80), Clinical Disease Activity Index 28.00 (19.50–32.00) and Simple Disease Activity Index 29.18 (19.51–33.05). All the patients included in the study were treated with upadacitinib at a dose of 15 mg once a day against the background of the therapy with methotrexate, leflunomide, non-steroidal anti-inflammatory drugs and glucocorticoids. Observation was carried out before treatment and after 3, 6 months of therapy. Serum levels of 15 cytokines: interleukin-1β, -4, -6, -10, -17A, -17F, -21, -22, -23, -25, -31, -33, tumor necrosis factor-alpha, interferon gamma, soluble СD40 ligand were studied using multiplex xMAP technology.
 RESULTS: After 3 and 6 months of upadacitinib therapy, there was a significant decrease in Disease Activity Score-28 with erythrocyte sedimentation rate 3.78 (2.53–4.20) and 3.5 (2.00–3.68), Clinical Disease Activity Index 12.00 (5.00–17.34) and 9.0 (3.00–11.00), Simple Disease Activity Index 12.38 (5.02–17.00) and 9.61 (3.06–11.60), erythrocyte sedimentation rate 19.0 (11.0–26.0), 7.0 (4.0–18.0), CRP 0.56 (0.50–1.99), 0.71 (0.51–1.1). The values of erythrocyte sedimentation rate decreased after 3 months of treatment (baseline 21.0 (15.0–25.0) mm/hour, after 3 months 14,0 (11,0–17,0) mm/hour. After 6 months of upadacitinib therapy, there was a significant decrease in interleukin-10 (p 0.05) and interleukin-33 (p 0.01) levels compared to baseline. On the contrary, the level of interleukin-25 increased by the 6th month of treatment (p 0.01).
 CONCLUSIONS: The results of the study indicate the effectiveness of upadacitinib in rheumatoid arthritis, and also provide grounds for further study of the pathogenetic mechanisms of cytokine-dependent inflammation in this disease.