Benedetta Saccomanno1,2, Jessica Tibaldi1,2, Francesca Minoia1,2, Francesca Bagnasco1,2, Angela Pistorio1,2, Andressa Guariento1,2, Roberta Caorsi1,2, Alessandro Consolaro1,2, Marco Gattorno1,2, Angelo Ravelli3,4. 1. From the Università degli Studi di Genova, and the Istituto Giannina Gaslini, Genoa; Fondazione Institute for Research and Health Care (IRCCS) Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Instituto de Criança - Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo, Brazil. 2. B. Saccomanno, MD, Research Fellow, Università degli Studi di Genova; J. Tibaldi, MD, PhD Student, Università degli Studi di Genova; F. Minoia, MD, Dirigente Medico, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; F. Bagnasco, PhD, Biostatistician, Istituto Giannina Gaslini; A. Pistorio, MD, PhD, Dirigente Medico, Istituto Giannina Gaslini; A. Guariento, MD, Research Fellow, Istituto Giannina Gaslini, and Instituto de Criança - FMUSP; R. Caorsi, MD, Dirigente Medico, Istituto Giannina Gaslini; A. Consolaro, MD, PhD, Assistant Professor, Università degli Studi di Genova and Istituto Giannina Gaslini; M. Gattorno, MD, Dirigente Medico, Istituto Giannina Gaslini; A. Ravelli, MD, Professor of Pediatrics, Università degli Studi di Genova and Istituto Giannina Gaslini. 3. From the Università degli Studi di Genova, and the Istituto Giannina Gaslini, Genoa; Fondazione Institute for Research and Health Care (IRCCS) Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; Instituto de Criança - Faculty of Medicine of the University of São Paulo (FMUSP), São Paulo, Brazil. angeloravelli@gaslini.org. 4. B. Saccomanno, MD, Research Fellow, Università degli Studi di Genova; J. Tibaldi, MD, PhD Student, Università degli Studi di Genova; F. Minoia, MD, Dirigente Medico, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; F. Bagnasco, PhD, Biostatistician, Istituto Giannina Gaslini; A. Pistorio, MD, PhD, Dirigente Medico, Istituto Giannina Gaslini; A. Guariento, MD, Research Fellow, Istituto Giannina Gaslini, and Instituto de Criança - FMUSP; R. Caorsi, MD, Dirigente Medico, Istituto Giannina Gaslini; A. Consolaro, MD, PhD, Assistant Professor, Università degli Studi di Genova and Istituto Giannina Gaslini; M. Gattorno, MD, Dirigente Medico, Istituto Giannina Gaslini; A. Ravelli, MD, Professor of Pediatrics, Università degli Studi di Genova and Istituto Giannina Gaslini. angeloravelli@gaslini.org.
Abstract
OBJECTIVE: To seek predictors of therapeutic response to the interleukin (IL)-1 inhibitor anakinra in children with systemic-onset juvenile idiopathic arthritis (sJIA). METHODS: The clinical charts of all patients with sJIA who were newly treated with anakinra at our center between 2004 and 2017 were reviewed retrospectively. Predictors included baseline demographic, clinical, and laboratory variables as well as previous or concomitant therapies. The effectiveness of anakinra was assessed at 1 year after treatment start. Complete clinical response (CCR) was defined as absence of fever, physician's global assessment ≤ 1, count of active joints ≤ 1, negative C-reactive protein, and ≥ 75% reduction of corticosteroid dose. According to the intention-to-treat principle, patients who had anakinra discontinued before 1 year for any reasons other than disease remission were classified as nonresponders. Statistics included univariate and multivariable analyses. RESULTS: Of the 62 patients included in the study, 24 (39%) met the criteria for CCR at 1 year, whereas 38 (61%) did not. On multivariable analysis, independent correlations with achievement of CCR were identified for shorter disease duration, lower active joint count, higher ferritin level, and greater activity of systemic manifestations. The area under the curve of the model was 0.83. CONCLUSION: Our findings help to delineate the clinical profile of patients with sJIA who are more likely to benefit from IL-1 blockade. They also underscore the need for studies aimed at examining the therapeutic role of early IL-1 inhibition and to identify biomarkers predicting response to either IL-1 or IL-6 antagonists.
OBJECTIVE: To seek predictors of therapeutic response to the interleukin (IL)-1 inhibitor anakinra in children with systemic-onset juvenile idiopathic arthritis (sJIA). METHODS: The clinical charts of all patients with sJIA who were newly treated with anakinra at our center between 2004 and 2017 were reviewed retrospectively. Predictors included baseline demographic, clinical, and laboratory variables as well as previous or concomitant therapies. The effectiveness of anakinra was assessed at 1 year after treatment start. Complete clinical response (CCR) was defined as absence of fever, physician's global assessment ≤ 1, count of active joints ≤ 1, negative C-reactive protein, and ≥ 75% reduction of corticosteroid dose. According to the intention-to-treat principle, patients who had anakinra discontinued before 1 year for any reasons other than disease remission were classified as nonresponders. Statistics included univariate and multivariable analyses. RESULTS: Of the 62 patients included in the study, 24 (39%) met the criteria for CCR at 1 year, whereas 38 (61%) did not. On multivariable analysis, independent correlations with achievement of CCR were identified for shorter disease duration, lower active joint count, higher ferritin level, and greater activity of systemic manifestations. The area under the curve of the model was 0.83. CONCLUSION: Our findings help to delineate the clinical profile of patients with sJIA who are more likely to benefit from IL-1 blockade. They also underscore the need for studies aimed at examining the therapeutic role of early IL-1 inhibition and to identify biomarkers predicting response to either IL-1 or IL-6 antagonists.
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