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Front Pharmacol. 2019 Jan 8;9:1526. doi: 10.3389/fphar.2018.01526. eCollection 2018.

Drug Retention Rate and Predictive Factors of Drug Survival for Interleukin-1 Inhibitors in Systemic Juvenile Idiopathic Arthritis.

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Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
Division of Rheumatology, Department of Pediatric Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Rheumatology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy.
Department of Pediatrics, University of Naples Federico II, Naples, Italy.
Pediatric Clinic, University of Brescia, Brescia, Italy.
Department of Pediatrics, Azienda Ospedaliera Universitaria Policlinico "G. Martino" - Messina, University of Messina, Messina, Italy.
Universitary Department "Pro.S.A.M.I.", University of Palermo, Palermo, Italy.
Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.
Pediatric Rheumatology Section, Pediatric Oncoematology Unit, Vito Fazzi Hospital, Lecce, Italy.
Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Seconda Università degli Studi di Napoli, Naples, Italy.
Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy.
Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMN, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, Italy.
Institute of Pediatrics, Periodic Fever Research Center, Università Cattolica Sacro Cuore, Fondazione Policlinico A. Gemelli, IRCCS, Rome, Italy.


Background and Objectives: Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA. Methods: Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers. Results: Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (p = 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (p = 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (p = 0.038) and when distinguishing according to adverse events (AEs) occurrence (p = 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 [CI: 1.341-8.406], p = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186-7.435], p = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (p = 0.0002). Conclusions: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.


anakinra; canakinumab; drug retention rate; interleukin 1-beta; systemic juvenile idiopathic arthritis; therapy

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