Efficacy and safety of discontinuation of tumor necrosis factor alpha inhibitors in long-term remission of juvenile idiopathic arthritis without systemic manifestations: a cohort study
Authors:   National Medical Research Center of Children's Health, Moscow, Russian Federation, Tsulukiya I.T. , Alexeeva E.I. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   Association of Pediatric Rheumatologists, Moscow, Russian Federation, Dvoryakovskaya T.M. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   Association of Pediatric Rheumatologists, Moscow, Russian Federation, Isaeva K.B. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation, Chomakhidze A.M. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation, Lomakina O.L. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation, Fetisova A.N. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation, Chibisova C.V. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation, Kriulin I.A. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Krekhova E.A. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation, Botova M.S. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation, Kondratyeva N.M. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Shingarova M.Sh. ,   National Medical Research Center of Children's Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
Published: March 2023

The biological agents when long-term clinical remission of juvenile idiopathic arthritis (JIA) is achieved is necessary to reduce the risk of side effects and costs and to minimize the non-economic burden of therapy on patients and their families. Objective. To evaluate the efficacy and safety of discontinuing inhibitors of tumor necrosis factor alpha (TNF-α) in patients with JIA without systemic manifestations due to long-term clinical remission. Patients and methods. A total of 137 patients with JIA (27.0% male, mean age: 10 years) were enrolled in this study, of whom 95 (69.3%) received etanercept (0.8 mg/kg/week) and the rest – adalimumab (24 mg/m2 once every two weeks). The retrospective study included patients with JIA without systemic manifestations and disease remission of ≥24 months, during which the patients received TNF-α inhibitors. The latter were discontinued as directed by a physician or due to unavailability of the drug. The primary outcome measure of the study was maintenance of clinically inactive disease status (according to American College of Rheumatology criteria) for 6 months (<210 days including 30 days’ tolerance for deviation from the recommended rehospitalization time) after discontinuation of therapy with TNF-α inhibitors. Results. At the time of TNF-α withdrawal, the median duration of JIA was about 6 years, the duration of TNF-α therapy was 3.5 years, and remission lasted for 3 years. After TNF-α withdrawal, 60 (43.8%) patients continued therapy with traditional disease-modifying antirheumatic drugs (DMARs). In the first 210 days after TNF-α discontinuation, 92 (67.2%) patients with JIA maintained the inactive disease status. The median time for the development of JIA exacerbations in 45 patients was 123 (95; 150) days. Biological agents therapy was resumed in 42 of 45 patients, and the inactive disease status was achieved in 41 cases. DMARs were received by 23 (55%) of 42 patients on therapy with biological agents. Conclusion. In two thirds of patients with JIA, the discontinuation of TNF-α inhibitors due to long-term clinical remission did not lead to disease exacerbations in the next six months. The resumption of biological agents therapy in case of JIA worsening allows most patients to reach the status of clinically inactive disease. Key words: genetically engineered biopharmaceutical drugs, tumor necrosis factor inhibitors, juvenile idiopathic arthritis, therapy withdrawal, long-term remission, clinically inactive disease