Frontiers in Pharmacology (Apr 2019)
Long-Term Retention Rate of Anakinra in Adult Onset Still’s Disease and Predictive Factors for Treatment Response
- Antonio Vitale,
- Giulio Cavalli,
- Giulio Cavalli,
- Serena Colafrancesco,
- Roberta Priori,
- Guido Valesini,
- Lorenza Maria Argolini,
- Elena Baldissera,
- Elena Bartoloni,
- Daniele Cammelli,
- Giovanni Canestrari,
- Jurgen Sota,
- Elena Cavallaro,
- Maria Grazia Massaro,
- Piero Ruscitti,
- Paola Cipriani,
- Ginevra De Marchi,
- Salvatore De Vita,
- Giacomo Emmi,
- Gianfranco Ferraccioli,
- Micol Frassi,
- Roberto Gerli,
- Elisa Gremese,
- Florenzo Iannone,
- Giovanni Lapadula,
- Giuseppe Lopalco,
- Raffaele Manna,
- Alessandro Mathieu,
- Carlomaurizio Montecucco,
- Marta Mosca,
- Ilaria Piazza,
- Matteo Piga,
- Irene Pontikaki,
- Micol Romano,
- Silvia Rossi,
- Maurizio Rossini,
- Elena Silvestri,
- Chiara Stagnaro,
- Rosaria Talarico,
- Angela Tincani,
- Ombretta Viapiana,
- Gianfranco Vitiello,
- Paola Galozzi,
- Paolo Sfriso,
- Carla Gaggiano,
- Donato Rigante,
- Lorenzo Dagna,
- Lorenzo Dagna,
- Roberto Giacomelli,
- Luca Cantarini
Affiliations
- Antonio Vitale
- Research Centre of Systemic Autoinflammatory Diseases, Behçet’s Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
- Giulio Cavalli
- Vita-Salute San Raffaele University, Milan, Italy
- Giulio Cavalli
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
- Serena Colafrancesco
- Rheumatology Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
- Roberta Priori
- Rheumatology Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
- Guido Valesini
- Rheumatology Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
- Lorenza Maria Argolini
- Division of Rheumatology, ASST Gaetano Pini, Milan, Italy
- Elena Baldissera
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
- Elena Bartoloni
- Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy
- Daniele Cammelli
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
- Giovanni Canestrari
- Institute of Rheumatology and Affine Sciences, Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy
- Jurgen Sota
- Research Centre of Systemic Autoinflammatory Diseases, Behçet’s Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
- Elena Cavallaro
- Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Udine, Italy
- Maria Grazia Massaro
- 0Periodic Fever Research Center, Institute of Internal Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, Italy
- Piero Ruscitti
- 1Department of Biotechnological and Applied Clinical Science, Division of Rheumatology, University of L’Aquila, L’Aquila, Italy
- Paola Cipriani
- 1Department of Biotechnological and Applied Clinical Science, Division of Rheumatology, University of L’Aquila, L’Aquila, Italy
- Ginevra De Marchi
- Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Udine, Italy
- Salvatore De Vita
- Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Udine, Italy
- Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
- Gianfranco Ferraccioli
- Institute of Rheumatology and Affine Sciences, Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy
- Micol Frassi
- 2Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Roberto Gerli
- Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy
- Elisa Gremese
- Institute of Rheumatology and Affine Sciences, Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy
- Florenzo Iannone
- 3Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- Giovanni Lapadula
- 3Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- Giuseppe Lopalco
- 3Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
- Raffaele Manna
- 0Periodic Fever Research Center, Institute of Internal Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, Italy
- Alessandro Mathieu
- 4Rheumatology Unit, Department of Medical Sciences, University and AOU of Cagliari, Cagliari, Italy
- Carlomaurizio Montecucco
- 5Department of Rheumatology, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
- Marta Mosca
- 6Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- Ilaria Piazza
- 7Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy
- Matteo Piga
- 4Rheumatology Unit, Department of Medical Sciences, University and AOU of Cagliari, Cagliari, Italy
- Irene Pontikaki
- Division of Rheumatology, ASST Gaetano Pini, Milan, Italy
- Micol Romano
- Division of Rheumatology, ASST Gaetano Pini, Milan, Italy
- Silvia Rossi
- 5Department of Rheumatology, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
- Maurizio Rossini
- 7Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy
- Elena Silvestri
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
- Chiara Stagnaro
- 6Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- Rosaria Talarico
- 6Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- Angela Tincani
- 2Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
- Ombretta Viapiana
- 7Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy
- Gianfranco Vitiello
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
- Paola Galozzi
- 8Department of Medicine DIMED, Rheumatology Unit, University of Padua, Padua, Italy
- Paolo Sfriso
- 8Department of Medicine DIMED, Rheumatology Unit, University of Padua, Padua, Italy
- Carla Gaggiano
- 9Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, Italy
- Donato Rigante
- 0Institute of Pediatrics, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli I.R.C.C.S., Rome, Italy
- Lorenzo Dagna
- Vita-Salute San Raffaele University, Milan, Italy
- Lorenzo Dagna
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
- Roberto Giacomelli
- 1Department of Biotechnological and Applied Clinical Science, Division of Rheumatology, University of L’Aquila, L’Aquila, Italy
- Luca Cantarini
- Research Centre of Systemic Autoinflammatory Diseases, Behçet’s Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
- DOI
- https://doi.org/10.3389/fphar.2019.00296
- Journal volume & issue
-
Vol. 10
Abstract
Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still’s disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission.Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission.Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed.Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043–1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058–0.863).Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.
Keywords
- autoinflammatory diseases
- systemic onset juvenile idiopathic arthritis
- personalized medicine
- canakinumab
- innovative biotechnologies
- interleukin-1