TY - JOUR T1 - Flares After Withdrawal of Biologic Therapies in Juvenile Idiopathic Arthritis: Clinical and Laboratory Correlates of Remission Duration. JF - Arthritis Care Res (Hoboken) Y1 - 2018 A1 - Simonini, Gabriele A1 - Ferrara, Giovanna A1 - Pontikaki, Irene A1 - Scoccimarro, Erika A1 - Giani, Teresa A1 - Taddio, Andrea A1 - Meroni, Pier Luigi A1 - Cimaz, Rolando AB -

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's signed rank test for paired samples, chi-square tests, and Fisher's exact test were used to compare data. Pearson's and Spearman'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 ± SD 18.64 ± 3.3 months versus 11.51 ± 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.

VL - 70 IS - 7 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28973842?dopt=Abstract ER - TY - JOUR T1 - Intra-articular corticosteroids versus intra-articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open-label trial. JF - Lancet Y1 - 2017 A1 - Ravelli, Angelo A1 - Davì, Sergio A1 - Bracciolini, Giulia A1 - Pistorio, Angela A1 - Consolaro, Alessandro A1 - van Dijkhuizen, Evert Hendrik Pieter A1 - Lattanzi, Bianca A1 - Filocamo, Giovanni A1 - Verazza, Sara A1 - Gerloni, Valeria A1 - Gattinara, Maurizio A1 - Pontikaki, Irene A1 - Insalaco, Antonella A1 - De Benedetti, Fabrizio A1 - Civino, Adele A1 - Presta, Giuseppe A1 - Breda, Luciana A1 - Marzetti, Valentina A1 - Pastore, Serena A1 - Magni-Manzoni, Silvia A1 - Maggio, Maria Cristina A1 - Garofalo, Franco A1 - Rigante, Donato A1 - Gattorno, Marco A1 - Malattia, Clara A1 - Picco, Paolo A1 - Viola, Stefania A1 - Lanni, Stefano A1 - Ruperto, Nicolino A1 - Martini, Alberto KW - Adrenal Cortex Hormones KW - Arthritis, Juvenile KW - Humans KW - Injections, Intra-Articular KW - Italy KW - Methotrexate KW - Prospective Studies KW - Treatment Outcome AB -

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=0·48). 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.

VL - 389 IS - 10072 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28162781?dopt=Abstract ER - TY - JOUR T1 - Safety and efficacy of infliximab and adalimumab for refractory uveitis in juvenile idiopathic arthritis: 1-year followup data from the Italian Registry. JF - J Rheumatol Y1 - 2013 A1 - Zannin, Maria E A1 - Birolo, Carolina A1 - Gerloni, Valeria M A1 - Miserocchi, Elisabetta A1 - Pontikaki, Irene A1 - Paroli, Maria P A1 - Bracaglia, Claudia A1 - Shardlow, Alison A1 - Parentin, Fulvio A1 - Cimaz, Rolando A1 - Simonini, Gabriele A1 - Falcini, Fernanda A1 - Corona, Fabrizia A1 - Viola, Stefania A1 - De Marco, Riccardo A1 - Breda, Luciana A1 - La Torre, Francesco A1 - Vittadello, Fabio A1 - Martini, Giorgia A1 - Zulian, Francesco KW - Adolescent KW - Antibodies, Monoclonal KW - Antibodies, Monoclonal, Humanized KW - Antirheumatic Agents KW - Arthritis, Juvenile KW - Child KW - Child, Preschool KW - Female KW - Follow-Up Studies KW - Humans KW - Infant KW - Italy KW - Male KW - Registries KW - Treatment Outcome KW - Tumor Necrosis Factor-alpha KW - Uveitis AB -

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' 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.

VL - 40 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23118110?dopt=Abstract ER -