Browsing by Author "Giancane, Gabriella"

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    Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis : Analysis by the Pharmachild Safety Adjudication Committee
    (2020-04-07) Giancane, Gabriella; Paediatric Rheumatology International Trials Organisation (PRINTO); Staņēviča, Valda
    Background: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies. Trial registration: Clinicaltrials.gov NCT 01399281; ENCePP seal: awarded on 25 November 2011.
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    Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs : combined data of more than 15,000 patients from Pharmachild and national registries
    (2018-12-27) Swart, Joost; Giancane, Gabriella; Horneff, Gerd; Magnusson, Bo; Hofer, Michael; Alexeeva, Ekaterina; Panaviene, Violeta; Bader-Meunier, Brigitte; Anton, Jordi; Nielsen, Susan; De Benedetti, Fabrizio; Kamphuis, Sylvia; Stanevica, Valda; Tracahana, Maria; Ailioaie, Laura Marinela; Tsitsami, Elena; Klein, Ariane; Minden, Kirsten; Foeldvari, Ivan; Haas, Johannes Peter; Klotsche, Jens; Horne, Anna Carin; Consolaro, Alessandro; Bovis, Francesca; Bagnasco, Francesca; Pistorio, Angela; Martini, Alberto; Wulffraat, Nico; Ruperto, Nicolino; Department of Paediatrics
    ackgroundThe availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden.MethodsDescriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available.ResultsData from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1-6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor-negative polyarthritis (range of 24.6-29.9%). Methotrexate (61-84%) and etanercept (24%-61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7-42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4-30.1%) followed by gastrointestinal disorders (11.5-19.6%). The most frequent ESIs were infections (75.3-89%).ConclusionsThis article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA.Registry registrationThe Pharmachild registry is registered at ClinicalTrials.gov (NCT01399281) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) (http://www.encepp.eu/encepp/viewResource.htm?id=19362). The BiKeR registry is registered at ENCePP (http://www.encepp.eu/encepp/viewResource.htm?id=20591).
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    The PRINTO evidence-based proposal for glucocorticoids tapering/discontinuation in new onset juvenile dermatomyositis patients
    (2019-05-22) Giancane, Gabriella; Lavarello, Claudio; Pistorio, Angela; Oliveira, Sheila K.; Zulian, Francesco; Cuttica, Ruben; Fischbach, Michel; Magnusson, Bo; Pastore, Serena; Marini, Roberto; Martino, Silvana; Pagnier, Anne; Soler, Christine; Stanevicha, Valda; Ten Cate, Rebecca; Uziel, Yosef; Vojinovic, Jelena; Fueri, Elena; Ravelli, Angelo; Martini, Alberto; Ruperto, Nicolino
    BackgroundPrednisone (PDN) in juvenile dermatomyositis (JDM), alone or in association with other immunosuppressive drugs, namely methotrexate (MTX) and cyclosporine (CSA), represents the first-line treatment option for new onset JDM patients. No clear evidence based guidelines are actually available to standardize the tapering and discontinuation of glucocorticoids (GC) in JDM. Aim of our study was to provide an evidence-based proposal for GC tapering/discontinuation in new onset juvenile dermatomyositis (JDM), and to identify predictors of clinical remission and GC discontinuation.MethodsNew onset JDM children were randomized to receive either PDN alone or in combination with methotrexate (MTX) or cyclosporine (CSA). In order to derive steroid tapering indications, PRINTO/ACR/EULAR JDM core set measures (CSM) and their median absolute and relative percent changes over time were compared in 3 groups. Group 1 included those in clinical remission who discontinued PDN, with no major therapeutic changes (MTC) (reference group) and was compared with those who did not achieve clinical remission, without or with MTC (Group 2 and 3, respectively). A logistic regression model identified predictors of clinical remission with PDN discontinuation.ResultsBased on the median change in the CSM of 30/139 children in Group 1, after 3 pulses of methyl-prednisolone, GC could be tapered from 2 to 1mg/kg/day in the first two months from onset if any of the CSM decreased by 50-94%, and from 1 to 0.2mg/kg/day in the following 4months if any CSM further decreased by 8-68%, followed by discontinuation in the ensuing 18months. The achievement of PRINTO JDM 50-70-90 response after 2months of treatment (ORs range 4.5-6.9), an age at onset >9years (OR 4.6) and the combination therapy PDN+MTX (OR 3.6) increase the probability of achieving clinical remission (p<0.05).ConclusionsThis is the first evidence-based proposal for glucocorticoid tapering/discontinuation based on the change in JDM CSM of disease activity.
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    The PRINTO evidence-based proposal for glucocorticoids tapering/discontinuation in new onset juvenile dermatomyositis patients
    (2019-05-22) Giancane, Gabriella; Lavarello, Claudio; Pistorio, Angela; Oliveira, Sheila K.; Zulian, Francesco; Cuttica, Ruben; Fischbach, Michel; Magnusson, Bo; Pastore, Serena; Marini, Roberto; Martino, Silvana; Pagnier, Anne; Soler, Christine; Stanevicha, Valda; Ten Cate, Rebecca; Uziel, Yosef; Vojinovic, Jelena; Fueri, Elena; Ravelli, Angelo; Martini, Alberto; Ruperto, Nicolino
    BackgroundPrednisone (PDN) in juvenile dermatomyositis (JDM), alone or in association with other immunosuppressive drugs, namely methotrexate (MTX) and cyclosporine (CSA), represents the first-line treatment option for new onset JDM patients. No clear evidence based guidelines are actually available to standardize the tapering and discontinuation of glucocorticoids (GC) in JDM. Aim of our study was to provide an evidence-based proposal for GC tapering/discontinuation in new onset juvenile dermatomyositis (JDM), and to identify predictors of clinical remission and GC discontinuation.MethodsNew onset JDM children were randomized to receive either PDN alone or in combination with methotrexate (MTX) or cyclosporine (CSA). In order to derive steroid tapering indications, PRINTO/ACR/EULAR JDM core set measures (CSM) and their median absolute and relative percent changes over time were compared in 3 groups. Group 1 included those in clinical remission who discontinued PDN, with no major therapeutic changes (MTC) (reference group) and was compared with those who did not achieve clinical remission, without or with MTC (Group 2 and 3, respectively). A logistic regression model identified predictors of clinical remission with PDN discontinuation.ResultsBased on the median change in the CSM of 30/139 children in Group 1, after 3 pulses of methyl-prednisolone, GC could be tapered from 2 to 1mg/kg/day in the first two months from onset if any of the CSM decreased by 50-94%, and from 1 to 0.2mg/kg/day in the following 4months if any CSM further decreased by 8-68%, followed by discontinuation in the ensuing 18months. The achievement of PRINTO JDM 50-70-90 response after 2months of treatment (ORs range 4.5-6.9), an age at onset >9years (OR 4.6) and the combination therapy PDN+MTX (OR 3.6) increase the probability of achieving clinical remission (p<0.05).ConclusionsThis is the first evidence-based proposal for glucocorticoid tapering/discontinuation based on the change in JDM CSM of disease activity.