Browsing by Author "Vojinovic, Jelena"

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    Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis : Part 1 (week 12) of the CLIPPER study
    (2014-06) Horneff, Gerd; Burgos-Vargas, Ruben; Constantin, Tamas; Foeldvari, Ivan; Vojinovic, Jelena; Chasnyk, Vyacheslav G.; Dehoorne, Joke; Panaviene, Violeta; Susic, Gordana; Stanevica, Valda; Kobusinska, Katarzyna; Zuber, Zbigniew; Mouy, Richard; Rumba-Rozenfelde, Ingrida; Breda, Luciana; Dolezalova, Pavla; Job-Deslandre, Chantal; Wulffraat, Nico; Alvarez, Daniel; Zang, Chuanbo; Wajdula, Joseph; Woodworth, Deborah; Vlahos, Bonnie; Martini, Alberto; Ruperto, Nicolino; Department of Paediatrics
    Objective To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitisrelated arthritis (ERA), or psoriatic arthritis (PsA). Methods: CLIPPER is an ongoing, Phase 3b, open-label, multicentre study; the 12-week (Part 1) data are reported here. Subjects with eoJIA (2-17 years), ERA (12-17 years), or PsA (12-17 years) received ETN 0.8 mg/kg once weekly (maximum 50 mg). Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology (ACR) 30 criteria at week 12; secondary outcomes included JIA ACR 50/70/90 and inactive disease. Results: 122/127 (96.1%) subjects completed the study (mean age 11.7 years). JIA ACR 30 (95% CI) was achieved by 88.6% (81.6% to 93.6%) of subjects overall; 89.7% (78.8% to 96.1%) with eoJIA, 83.3% (67.2% to 93.6%) with ERA and 93.1% (77.2% to 99.2%) with PsA. For eoJIA, ERA, or PsA categories, the ORs of ETN vs the historical placebo data were 26.2, 15.1 and 40.7, respectively. Overall JIA ACR 50, 70, 90 and inactive disease were achieved by 81.1, 61.5, 29.8 and 12.1%, respectively. Treatment-emergent adverse events (AEs), infections, and serious AEs, were reported in 45 (35.4%), 58 (45.7%), and 4 (3.1%), subjects, respectively. Serious AEs were one case each of abdominal pain, bronchopneumonia, gastroenteritis and pyelocystitis. One subject reported herpes zoster and another varicella. No differences in safety were observed across the JIA categories. Conclusions: ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA, ERA and PsA, with no unexpected safety findings.
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    Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission a randomized clinical trial
    (2010-04-07) Foell, Dirk; Wulffraat, Nico; Wedderburn, Lucy R.; Wittkowski, Helmut; Frosch, Michael; Gerß, Joachim; Stanevicha, Valda; Mihaylova, Dimitrina; Ferriani, Virginia; Tsakalidou, Florence Kanakoudi; Foeldvari, Ivan; Cuttica, Ruben; Gonzalez, Benito; Ravelli, Angelo; Khubchandani, Raju; Oliveira, Sheila; Armbrust, Wineke; Garay, Stella; Vojinovic, Jelena; Norambuena, Ximena; Gamir, María Luz; García-Consuegra, Julia; Lepore, Loredana; Susic, Gordana; Corona, Fabrizia; Dolezalova, Pavla; Pistorio, Angela; Martini, Alberto; Ruperto, Nicolino; Roth, Johannes; Rīga Stradiņš University
    Context Novel therapies have improved the remission rate in chronic inflammatory disorders including juvenile idiopathic arthritis (JIA). Therefore, strategies of tapering therapy and reliable parameters for detecting subclinical inflammation have now become challenging questions. Objectives To analyze whether longer methotrexate treatment during remission of JIA prevents flares after withdrawal of medication and whether specific biomarkers identify patients at risk for flares. Design, Setting, and Patients Prospective, open, multicenter, medicationwithdrawal randomized clinical trial including 364 patients (median age, 11.0 years) with JIA recruited in 61 centers from 29 countries between February 2005 and June 2006. Patients were included at first confirmation of clinical remission while continuing medication. At the time of therapy withdrawal, levels of the phagocyte activation marker myeloidrelated proteins 8 and 14 heterocomplex (MRP8/14) were determined. Intervention Patients were randomly assigned to continue with methotrexate therapy for either 6 months (group 1 [n=183]) or 12 months (group 2 [n=181]) after induction of disease remission. Main Outcome Measures Primary outcome was relapse rate in the 2 treatment groups; secondary outcome was time to relapse. In a prespecified cohort analysis, the prognostic accuracy of MRP8/14 concentrations for the risk of flares was assessed. Results Intention-to-treat analysis of the primary outcome revealed relapse within 24 months after the inclusion into the study in 98 of 183 patients (relapse rate, 56.7%) in group 1 and 94 of 181 (55.6%) in group 2. The odds ratio for group 1 vs group 2 was 1.02 (95% CI, 0.82-1.27; P=.86). The median relapse-free interval after inclusion was 21.0 months in group 1 and 23.0 months in group 2. The hazard ratio for group 1 vs group 2 was 1.07 (95% CI, 0.82-1.41; P=.61). Median follow-up duration after inclusion was 34.2 and 34.3 months in groups 1 and 2, respectively. Levels of MRP8/14 during remission were significantly higher in patients who subsequently developed flares (median, 715 [IQR, 320-1110] ng/mL) compared with patients maintaining stable remission (400 [IQR, 220-800] ng/mL; P=.003). Low MRP8/14 levels indicated a low risk of flares within the next 3 months following the biomarker test (area under the receiver operating characteristic curve, 0.76; 95% CI, 0.62-0.90). Conclusions In patients with JIA in remission, a 12-month vs 6-month withdrawal of methotrexate did not reduce the relapse rate. Higher MRP8/14 concentrations were associated with risk of relapse after discontinuing methotrexate. Trial Registration isrctn.org Identifier: ISRCTN18186313.
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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.