Jurgen Sota1, Donato Rigante2,3, Rolando Cimaz4, Marco Cattalini5, Micol Frassi6, Raffaele Manna7, Ludovico Luca Sicignano8, Elena Verrecchia8, Emma Aragona9, Maria Cristina Maggio10, Giuseppe Lopalco11, Giacomo Emmi12, Paola Parronchi12, Alberto Cauli13, Ewa Wiesik-Szewczyk14, José Hernández-Rodríguez15, Carla Gaggiano1,16, Maria Tarsia16, Mariam Mourabi1, Gaafar Ragab17, Antonio Vitale1, Claudia Fabiani18, Bruno Frediani19, Vittoria Lamacchia20, Alessandra Renieri20,21, Luca Cantarini1. 1. Research Centre of Systemic Autoinflammatory Diseases and Behçet's Disease and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena. 2. Department of Life Sciences and Public Health, Fondazione Policlinico A. Gemelli IRCCS. 3. Università Cattolica Sacro Cuore, Rome. 4. ASST G. Pini-CTO, Department of Clinical Sciences and Community Health, Research Centre for Adult and Paediatric Rheumatic Diseases, University of Milan, Milan. 5. Pediatric Clinic, University of Brescia and Spedali Civili di Brescia. 6. Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, University of Brescia, Brescia. 7. Institute of Internal Medicine, Periodic Fever Research Centre, Fondazione Policlinico A. Gemelli, Università Cattolica Sacro Cuore. 8. UOC Continuità Assistenziale, Dipartimento di scienze dell'invecchiamento, neurologiche, ortopediche e della testa-collo, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome. 9. Division of Gastroenterology, DIBIMIS, Ospedali Riuniti Villa Sofia-Vincenzo Cervello. 10. Universitary Department 'Pro.S.A.M.I.', University of Palermo, Palermo. 11. Rheumatology Unit, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari. 12. Department of Experimental and Clinical Medicine, University of Florence, Florence. 13. Dipartimento di Scienze Mediche e Sanità Pubblica, Università di Cagliari, Cagliari, Italy. 14. Department of Internal Medicine, Pulmonology, Allergy and Clinical Immunology, Central Clinical Hospital of the Ministry of National Defence, Military Institute of Medicine, Warsaw, Poland. 15. Vasculitis Research Unit and Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Hospital Clinic of Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain. 16. Clinical Paediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, Italy. 17. Rheumatology and Clinical Immunology Unit, Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt. 18. Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena. 19. Department of Rheumatology, Policlinico Le Scotte, Azienda Ospedaliera Universitaria Senese. 20. Medical Genetics, University of Siena. 21. Genetica Medica, Azienda Ospedaliera Universitaria Senese, Siena, Italy.
Abstract
OBJECTIVES: To investigate survival of IL-1 inhibitors in monogenic autoinflammatory disorders (mAID) through drug retention rate (DRR) and identify potential predictive factors of drug survival from a real-life perspective. PATIENTS AND METHODS: Multicentre retrospective study analysing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analysed with the Kaplan-Meier method. Statistical analysis included a Cox-proportional hazard model to detect factors responsible for drug discontinuation. RESULTS: Seventy-eight patients for a total of 102 treatment regimens were enrolled. The mean treatment duration was 29.59 months. The estimated DRR of IL-1 inhibitors at 12, 24 and 48 months of follow-up was 75.8%, 69.7% and 51.1%, respectively. Patients experiencing an adverse event had a significantly lower DRR (P=0.019). In contrast, no significant differences were observed between biologic-naïve patients and those previously treated with biologic drugs (P=0.985). Patients carrying high-penetrance mutations exhibited a significantly higher DRR compared with those with low-penetrance variants (P=0.015). Adverse events were the only variable associated with a higher hazard of treatment withdrawal [hazard ratio (HR) 2.573 (CI: 1.223, 5.411), P=0.013] on regression analysis. A significant glucorticoid-sparing effect was observed (P<0.0001). CONCLUSIONS: IL-1 inhibitors display an excellent long-term effectiveness in terms of DRR, and their survival is not influenced by the biologic line of treatment. They display a favourable safety profile, which deserves, however, a close monitoring given its impact on treatment continuation. Special attention should be paid to molecular diagnosis and mutation penetrance, as patients carrying low-penetrance variants are more likely to interrupt treatment.
OBJECTIVES: To investigate survival of IL-1 inhibitors in monogenic autoinflammatory disorders (mAID) through drug retention rate (DRR) and identify potential predictive factors of drug survival from a real-life perspective. PATIENTS AND METHODS: Multicentre retrospective study analysing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analysed with the Kaplan-Meier method. Statistical analysis included a Cox-proportional hazard model to detect factors responsible for drug discontinuation. RESULTS: Seventy-eight patients for a total of 102 treatment regimens were enrolled. The mean treatment duration was 29.59 months. The estimated DRR of IL-1 inhibitors at 12, 24 and 48 months of follow-up was 75.8%, 69.7% and 51.1%, respectively. Patients experiencing an adverse event had a significantly lower DRR (P=0.019). In contrast, no significant differences were observed between biologic-naïve patients and those previously treated with biologic drugs (P=0.985). Patients carrying high-penetrance mutations exhibited a significantly higher DRR compared with those with low-penetrance variants (P=0.015). Adverse events were the only variable associated with a higher hazard of treatment withdrawal [hazard ratio (HR) 2.573 (CI: 1.223, 5.411), P=0.013] on regression analysis. A significant glucorticoid-sparing effect was observed (P<0.0001). CONCLUSIONS: IL-1 inhibitors display an excellent long-term effectiveness in terms of DRR, and their survival is not influenced by the biologic line of treatment. They display a favourable safety profile, which deserves, however, a close monitoring given its impact on treatment continuation. Special attention should be paid to molecular diagnosis and mutation penetrance, as patients carrying low-penetrance variants are more likely to interrupt treatment.