Predictors of remission in children with systemic juvenile idiopathic arthritis receiving biologicals (tocilizumab and canakinumab): a cohort study
Authors:   National Medical Research Center for Children's Health, Moscow, Russian Federation, Krekhova E.A. ,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation, Alexeeva E.I. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   Russian Association of Pediatric Rheumatologists, Moscow, Russian Federation, Dvoryakovskaya T.M. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation,   I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation,   Russian Association of Pediatric Rheumatologists, Moscow, Russian Federation, Isaeva K.B. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation, Denisova R.V. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation, Chomakhidze A.L. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation, Lomakina O.L. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation, Mamutova A.V. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation, Fetisova A.N. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation, Gautier M.S. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation, Chibisova K.V. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation, Kriulin I.A. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation, Tsulukiya I.T. ,   National Medical Research Center for Children's Health, Moscow, Russian Federation,   National Medical Research Center for Children's Health, Moscow, Russian Federation
Published: April 2022

Therapy with biologicals at the onset of systemic juvenile idiopathic arthritis (sJIA) ensures faster achievement of inactive disease or remission in more patients compared to standard treatment. Identification of predictors of early response to biologicals is necessary to increase treatment efficacy in children with sJIA. Objective. To develop a model for predicting treatment outcomes with different biologicals in sJIA patients. Materials and methods. We analyzed medical records of sJIA patients who received tocilizumab or canakinumab and were admitted to the Department of Rheumatology between July 2009 and February 2021. Predicted outcomes included inactive disease after 12 months of therapy with biologicals (according to C. Wallace criteria and JADAS71) and drug-free remission (without biologicals) for at least 6 months. Potential predictors comprised patient demographic and clinical characteristics, such as sJIA activity, CHAQ index, concomitant therapy, treatment outcomes after 1 and 3 months of therapy, etc. (115 parameters in total). Independent predictors were chosen using multivariate binary logistic regression. Results. This study included 250 patients receiving tocilizumab and 73 patients receiving canakinumab. After 12 months of tocilizumab therapy, 179 patients (76%) achieved inactive disease according to C. Wallace criteria and 170 patients (72%) achieved remission according to JADAS71 index. Drug-free remission (for at least 6 months without biologicals) was registered in 51 patients (20%) from the tocilizumab group. In the canakinumab group, inactive disease according to C. Wallace criteria, remission according to JADAS71, and drug-free remission were achieved in 58 (79%), 58 (79%), and 10 (14%) patients, respectively. Duration of morning stiffness at sJIA onset, dynamics of the duration of morning stiffness after 1 and 3 months of treatment, disease activity evaluated by a physician using the 100-mm visual analog scale (VAS) after one month of therapy, and patientreported overall well-being evaluated using VAS after 3 months of therapy were found to be the predictors of achieving remission according to C. Wallace criteria in the tocilizumab group. The following factors were significantly associated with remission according to JADAS71 index: duration of morning stiffness at sJIA onset and upon treatment initiation, VAS score evaluated by a physician after 1 and 3 months, and number of painful joints after 3 months. We also found several predictors of achieving drug-free remission, including lymphocyte count at disease onset, therapy with glucocorticoids (GCs) and its duration by the time of biological initiation, ESR upon treatment initiation, 50% improvement according to ACR pediatric criteria after 1 month, administration of systemic GCs after 1 month, ESR dynamics by 3 months, and number of joints with limited motion after 3 months. In the canakinumab group, the following factors were associated with remission according to C.Wallace criteria and JADAS71: duration of morning stiffness at treatment initiation, number of biologicals received in the past, 30% improvement according to pediatric ACR criteria after 1 month, and presence of joints with limited motion after 3 months; the predictors of drug-free remission included previous treatment with tocilizumab, number of active joints, and patient-reported overall well-being evaluated using VAS at treatment initiation, dynamics of the number of joints with active arthritis after 1 and 3 months, dynamics of JADAS71 after 1 month, lymphadenopathy after 1 month, and dynamics of patient-reported overall well-being after 3 months. Conclusion. Treatment in the past, characteristics of joint syndrome before and 1–3 months following treatment initiation, dynamics of laboratory parameters and VAS scores of disease activity (both patient-reported and physician-rated) were independent predictors of remission in sJIA patients during therapy with tocilizumab and canakinumab. Key words: systemic juvenile idiopathic arthritis, remission, predictors, biologicals, interleukin-1b inhibitor, interleukin-6 receptor inhibitor, tocilizumab, canakinumab