@article {10579, title = {Flares After Withdrawal of Biologic Therapies in Juvenile Idiopathic Arthritis: Clinical and Laboratory Correlates of Remission Duration.}, journal = {Arthritis Care Res (Hoboken)}, volume = {70}, year = {2018}, month = {2018 Jul}, pages = {1046-1051}, abstract = {

OBJECTIVE: To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA).

METHODS: We enrolled 135 patients followed in 3 tertiary-care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann-Whitney U test, Wilcoxon{\textquoteright}s signed rank test for paired samples, chi-square tests, and Fisher{\textquoteright}s exact test were used to compare data. Pearson{\textquoteright}s and Spearman{\textquoteright}s correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan-Meier curves were constructed, each one at the mean of entered covariates.

RESULTS: The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6\%) after a median followup time in remission off therapy of 6 months (range 3-109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic-onset disease compared to the rest of the JIA patients (Mantel-Cox χ = 8.31, P < 0.004). In analysis limited to children with JIA with polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean {\textpm} SD 18.64 {\textpm} 3.3 months versus 11.51 {\textpm} 2.7 months [P < 0.009]; Mantel-Cox χ = 9.06, P < 0.002). No other clinical variable was significantly associated with a long-lasting remission.

CONCLUSION: Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal.

}, issn = {2151-4658}, doi = {10.1002/acr.23435}, author = {Simonini, Gabriele and Ferrara, Giovanna and Pontikaki, Irene and Scoccimarro, Erika and Giani, Teresa and Taddio, Andrea and Meroni, Pier Luigi and Cimaz, Rolando} } @article {10555, title = {Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial.}, journal = {Lancet}, volume = {389}, year = {2017}, month = {2017 03 04}, pages = {909-916}, abstract = {

BACKGROUND: Little evidence-based information is available to guide the treatment of oligoarticular juvenile idiopathic arthritis. We aimed to investigate whether oral methotrexate increases the efficacy of intra-articular corticosteroid therapy.

METHODS: We did this prospective, open-label, randomised trial at ten hospitals in Italy. Using a concealed computer-generated list, children younger than 18 years with oligoarticular-onset disease were randomly assigned (1:1) to intra-articular corticosteroids alone or in combination with oral methotrexate (15 mg/m; maximum 20 mg). Corticosteroids used were triamcinolone hexacetonide (shoulder, elbow, wrist, knee, and tibiotalar joints) or methylprednisolone acetate (ie, subtalar and tarsal joints). We did not mask patients or investigators to treatment assignments. Our primary outcome was the proportion of patients in the intention-to-treat population who had remission of arthritis in all injected joints at 12 months. This trial is registered with European Union Clinical Trials Register, EudraCT number 2008-006741-70.

FINDINGS: Between July 7, 2009, and March 31, 2013, we screened 226 participants and randomly assigned 102 to intra-articular corticosteroids alone and 105 to intra-articular corticosteroids plus methotrexate. 33 (32\%) patients assigned to intra-articular corticosteroids alone and 39 (37\%) assigned to intra-articular corticosteroids and methotrexate therapy had remission of arthritis in all injected joints (p=0{\textperiodcentered}48). Adverse events were recorded for 20 (17\%) patients who received methotrexate, which led to permanent treatment discontinuation in two patients (one due to increased liver transaminases and one due to gastrointestinal discomfort). No patient had a serious adverse event.

INTERPRETATION: Concomitant administration of methotrexate did not augment the effectiveness of intra-articular corticosteroid therapy. Future studies are needed to define the optimal therapeutic strategies for oligoarticular juvenile idiopathic arthritis.

FUNDING: Italian Agency of Drug Evaluation.

}, keywords = {Adrenal Cortex Hormones, Arthritis, Juvenile, Humans, Injections, Intra-Articular, Italy, Methotrexate, Prospective Studies, Treatment Outcome}, issn = {1474-547X}, doi = {10.1016/S0140-6736(17)30065-X}, author = {Ravelli, Angelo and Dav{\`\i}, Sergio and Bracciolini, Giulia and Pistorio, Angela and Consolaro, Alessandro and van Dijkhuizen, Evert Hendrik Pieter and Lattanzi, Bianca and Filocamo, Giovanni and Verazza, Sara and Gerloni, Valeria and Gattinara, Maurizio and Pontikaki, Irene and Insalaco, Antonella and De Benedetti, Fabrizio and Civino, Adele and Presta, Giuseppe and Breda, Luciana and Marzetti, Valentina and Pastore, Serena and Magni-Manzoni, Silvia and Maggio, Maria Cristina and Garofalo, Franco and Rigante, Donato and Gattorno, Marco and Malattia, Clara and Picco, Paolo and Viola, Stefania and Lanni, Stefano and Ruperto, Nicolino and Martini, Alberto} } @article {1991, title = {Safety and efficacy of infliximab and adalimumab for refractory uveitis in juvenile idiopathic arthritis: 1-year followup data from the Italian Registry.}, journal = {J Rheumatol}, volume = {40}, year = {2013}, month = {2013 Jan}, pages = {74-9}, abstract = {

OBJECTIVE: To evaluate safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of juvenile idiopathic arthritis-related anterior uveitis (JIA-AU).

METHODS: Starting January 2007, patients with JIA-AU treated with IFX and ADA were managed by a standard protocol and data were entered into the National Italian Registry (NIR). At baseline, all patients were refractory to standard immunosuppressive treatment and/or were corticosteroid-dependent. Data recorded every 3 months included uveitis course, number/type of ocular complications, drug-related adverse events (AE), treatment change or withdrawal, and laboratory measures. Data of patients treated for at least 1 year were retrieved from the NIR and analyzed using descriptive statistics. Treatment efficacy was based on change in uveitis course and in number of ocular complications.

RESULTS: Up to December 2009, data for 108 patients with JIA-AU treated with anti-tumor necrosis factor-α agents were recorded in the NIR and data from 91, with at least 12 months{\textquoteright} followup, were included in the study. Forty-eight patients were treated with IFX, 43 with ADA. Forty-seven patients (55.3\%) achieved remission of AU, 28 (32.9\%) had recurrent AU, and 10 (11.8\%) maintained a chronic course. A higher remission rate was observed with ADA (67.4\% vs 42.8\% with IFX; p = 0.025). Ocular complications decreased from 0.47 to 0.32 per subject. Five patients experienced resolution of structural complications. No patient reported serious AE; 8 (8.8\%) experienced 11 minor AE (9 with IFX, 2 with ADA).

CONCLUSION: IFX and ADA appear to be effective and safe for treatment of refractory JIA-related uveitis, with a better performance of ADA in the medium-term period.

}, keywords = {Adolescent, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antirheumatic Agents, Arthritis, Juvenile, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Italy, Male, Registries, Treatment Outcome, Tumor Necrosis Factor-alpha, Uveitis}, issn = {0315-162X}, doi = {10.3899/jrheum.120583}, author = {Zannin, Maria E and Birolo, Carolina and Gerloni, Valeria M and Miserocchi, Elisabetta and Pontikaki, Irene and Paroli, Maria P and Bracaglia, Claudia and Shardlow, Alison and Parentin, Fulvio and Cimaz, Rolando and Simonini, Gabriele and Falcini, Fernanda and Corona, Fabrizia and Viola, Stefania and De Marco, Riccardo and Breda, Luciana and La Torre, Francesco and Vittadello, Fabio and Martini, Giorgia and Zulian, Francesco} }