0000000000129054
AUTHOR
Raffaele Manna
Anakinra drug retention rate and predictive factors of long-term response in systemic juvenile idiopathic arthritis and adult onset still disease
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 7…
Novel assay to diagnose and monitor cryopyrin associated periodic syndromes (CAPS)
Introduction: Cryopyrin associated periodic syndromes (CAPS) are rare autoinflammatory disorders associated with dominantly gain-offunction mutations in the NLRP3 gene that result in overactivation of the inflammasome, increased secretion of interleukin (IL)-1beta and IL-18, and systemic inflammation. It has been reported that oligomeric particles of the adaptor ASC (apoptosis-associated Speck-like protein with a caspase-recruitment domain) are released together with IL-1beta and active caspase-1 subunits after activation of the inflammosome complex and that patients with CAPS show an increased serum concentration of ASC+ particles. Objectives: The diagnosis of CAPS is a critical factor due…
Drug survival of anakinra and canakinumab in monogenic autoinflammatory diseases: observational study from the International AIDA Registry
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 D…
A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide Multi-Center Retrospective Observational Study
Background: Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis. Objectives: To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults. Methods: We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016. Results: Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA wa…
Home infusion program with enzyme replacement therapy for Fabry disease: The experience of a large Italian collaborative group
Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of clinical benefits, life-long intravenous (IV) treatment with ERT with an every other week schedule, may interfere with daily life activities and impact on QoL. We report here a multicentric, observational, longitudinal data analysis on a large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20 Italian regions, who received a cumulative number of 4269 home infu…
Role of Colchicine Treatment in Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS): Real-Life Data from the AIDA Network
Objective. To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Methods. Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. Results. 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in …
Clinical Features at Onset and Genetic Characterization of Pediatric and Adult Patients with TNF-α Receptor—Associated Periodic Syndrome (TRAPS): A Series of 80 Cases from the AIDA Network
This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian referral Centers. Patients’ data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p<0.05…
EVALUATION OF SERUM LEVELS OF ASC FOR THE DIAGNOSIS AND MONITORING OF CRYOPYRIN ASSOCIATED PERIODIC SYNDROMES (CAPS)
Background: Dominantly gain-of-function mutations in the NLRP3 gene lead to Cryopyrin associated periodic syndromes (CAPS) characterized by constitutive activation of the inflammasome, increased secretion of interleukin (IL)-1beta and IL-18, and systemic inflammation. IL-1beta and active caspase-1 subunits are released in the serum together with the oligomeric particles of the adaptor ASC (apoptosis-associated Speck-like protein with a caspase-recruitment domain) after activation of the inflammosome complex and, as a consequence, patients with CAPS show an increased serum concentration of ASC+ particles. Objectives: Patients suffering from CAPS are characterized by clinical manifestation si…
Biotechnological Agents for Patients With Tumor Necrosis Factor Receptor Associated Periodic Syndrome-Therapeutic Outcome and Predictors of Response: Real-Life Data From the AIDA Network
Objective: To describe the role of biotechnological therapies in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and to identify any predictor of complete response.Methods: Clinical, laboratory, and therapeutic data from 44 Caucasian TRAPS patients treated with biologic agents were retrospectively collected in 16 Italian tertiary Centers.Results: A total of 55 biological courses with anakinra (n = 26), canakinumab (n = 16), anti-TNF-α agents (n = 10), and tocilizumab (n = 3) were analyzed. A complete response was observed in 41 (74.5%) cases, a partial response in 9 (16.4%) cases and a treatment failure in 5 (9.1%) cases. The frequency of TRAPS exacerbation…
Anakinra drug retention rate and predictive factors of drug survival in systemic juvenile idiopathic arthritis and adult onset Still’s disease.
Introduction: Only a few studies have reported the long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult onset Still’s disease (AOSD). We herein describe Anakinra (ANA) effectiveness expressed in terms of drug retention rate (DRR) and evaluate predictive factors of drug survival in sJIA and ASOD patients. Objectives: Examine the overall DRR of ANA in sJIA and AOSD patients. Explore the influence of biologic line of treatment, and the concomitant use of disease modifying anti-rheumatic drugs (cDMARDs) on DRR in the whole sample and stratified according to the disease thereafter; find eventual predictive factors associated with events l…