Anakinra Drug Retention Rate and Predictive Factors of Long-Term Response in Systemic Juvenile Idiopathic Arthritis and Adult Onset Still Disease

Jurgen Sota; Donato Rigante; Piero Ruscitti; Antonella Insalaco; Paolo Sfriso; Salvatore de Vita; Rolando Cimaz; Giuseppe Lopalco; Giacomo Emmi; Francesco La Torre; Claudia Fabiani; Alma Nunzia Olivieri; Marco Cattalini; Daniele Cammelli; Romina Gallizzi; Maria Alessio; Raffaele Manna; Ombretta Viapiana; Micol Frassi; Manuela Pardeo; Armin Maier; Carlo Salvarani; Rosaria Talarico; Marta Mosca; Serena Colafrancesco; Roberta Priori; Maria Cristina Maggio; Carla Gaggiano; Salvatore Grosso; Fabrizio De Benedetti; Antonio Vitale; Roberto Giacomelli; Luca Cantarini

doi:10.3389/fphar.2019.00918

Anakinra Drug Retention Rate and Predictive Factors of Long-Term Response in Systemic Juvenile Idiopathic Arthritis and Adult Onset Still Disease

Front Pharmacol. 2019 Aug 23:10:918. doi: 10.3389/fphar.2019.00918. eCollection 2019.

Authors

Jurgen Sota¹, Donato Rigante^{2

3}, Piero Ruscitti⁴, Antonella Insalaco⁵, Paolo Sfriso⁶, Salvatore de Vita⁷, Rolando Cimaz⁸, Giuseppe Lopalco⁹, Giacomo Emmi¹⁰, Francesco La Torre¹¹, Claudia Fabiani¹², Alma Nunzia Olivieri¹³, Marco Cattalini¹⁴, Daniele Cammelli¹⁵, Romina Gallizzi¹⁶, Maria Alessio¹⁷, Raffaele Manna³, Ombretta Viapiana¹⁸, Micol Frassi¹⁹, Manuela Pardeo⁵, Armin Maier²⁰, Carlo Salvarani²¹, Rosaria Talarico²², Marta Mosca²², Serena Colafrancesco²³, Roberta Priori²³, Maria Cristina Maggio²⁴, Carla Gaggiano²⁵, Salvatore Grosso²⁵, Fabrizio De Benedetti⁵, Antonio Vitale¹, Roberto Giacomelli⁴, Luca Cantarini¹

Affiliations

¹ Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
² Institute of Pediatrics, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.
³ Periodic Fever Research Center, Università Cattolica Sacro Cuore, Rome, Italy.
⁴ Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, University of L'Aquila, L'Aquila, Italy.
⁵ Division of Rheumatology, Department of Pediatric Medicine, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
⁶ Rheumatology Unit, Department of Medicine, University of Padua, Padua, Italy.
⁷ Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Udine, Italy.
⁸ Rheumatology Unit, Meyer Children's Hospital, University of Florence, Florence, Italy.
⁹ Department of Emergency and Organ Transplantation-Rheumatology Unit, University of Bari, Bari, Italy.
¹⁰ Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
¹¹ Pediatric Rheumatology Section, Pediatric Unit, Giovanni XXIII - Pediatric Hospital, Bari, Italy.
¹² Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
¹³ Dipartimento della donna del bambino e di chirurgia generale e specialistica, Università della Campania Luigi Vanvitelli, Italy.
¹⁴ Pediatric Clinic, University of Brescia and Spedali Civili di Brescia, Brescia, Italy.
¹⁵ Experimental and Clinical Medicine Department, University of Florence, Florence, Italy.
¹⁶ Department of Pediatrics, Azienda G. Martino, University of Messina, Messina, Italy.
¹⁷ Department of Pediatrics, University Federico II, Naples, Italy.
¹⁸ Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy.
¹⁹ Rheumatology and Clinical Immunology Unit, Department of Clinical and Experimental Sciences, University of Brescia and Spedali Civili di Brescia, Brescia, Italy.
²⁰ Struttura Semplice di Reumatologia, Ospedale di Bolzano, Bolzano, Italy.
²¹ Rheumatology Unit, Department of Internal Medicine, Azienda Ospedaliera ASMN IRCCS, Reggio Emilia, Italy.
²² Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
²³ Department of Internal Medicine and Medical Specialties, Rheumatology Unit, Sapienza University of Rome, Rome, Italy.
²⁴ Universitary Department "Pro.S.A.M.I.", University of Palermo, Palermo, Italy.
²⁵ Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, Italy.

Abstract

Background and Objective: Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still disease (AOSD). Herein we report on the effectiveness of anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD. Patients and Methods: This is a multicenter study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers. Results: The cumulative retention rate of ANA at 12-, 24-, 48-, and 60-month of follow-up was 74.3%, 62.9%, 49.4%, and 49.4%, respectively, without any significant differences between sJIA and AOSD patients (p = 0.164), and between patients treated in monotherapy compared with the subgroup coadministered with conventional disease-modifying antirheumatic drugs (cDMARDs) (p = 0.473). On the other hand, a significant difference in DRR was found between biologic-naïve patients and those previously treated with biotechnologic drugs (p = 0.009), which persisted even after adjustment for pathology (p = 0.013). In the regression analysis, patients experiencing adverse events (AEs) {hazards ratio (HR) = 3.029 [confidence interval (CI) 1.750-5.242], p < 0.0001} and those previously treated with other biologic agents [HR = 1.818 (CI 1.007-3.282), p = 0.047] were associated with a higher HR of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (p < 0.0001). Significant corticosteroid-sparing (p = 0.033) and cDMARD-sparing effects (p < 0.0001) were also recorded. Less than one-third of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin. Conclusions: Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patient's safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant drug-sparing effect and showed an overall good safety profile.

Keywords: adult onset Still disease; anakinra; drug retention rate; innovative biotechnologies; interleukin 1-beta; personalized medicine; systemic juvenile idiopathic arthritis.