In our 6-year study, anti-TNFalpha agents infliximab and etanercept were well tolerated and safe, and were associated with only few serious, but all reversible, AEs. However, such inhibitors are associated with various and numerous AEs. Children and young adults affected by JIA should be carefully monitored so as to limit the risk of AEs during anti-TNFalpha therapy as much as possible.

Objectives: To describe demographic, clinical and therapeutic findings of a large cohort of patients with JIA-associated uveitis in a nationwide referral pediatric rheumatology and uveitis center in Northern Italy.Methods: Retrospective study of 125 patients with JIA-associated uveitis followed from 2009 to 2019. Demographic and rheumatologic features including JIA ILAR classification, age at onset, and laboratory data were recorded. Ocular findings collected were: anatomic location of uveitis, laterality, type, recurrence rate, visual acuity, ocular complications, and local therapy. Systemic therapy with conventional and biologic immunosuppressants, occurrence of adverse events, and duration of treatments were recorded.Results: One hundred and twenty-five patients with JIA-associated uveitis were followed for a meantime of 9.2 (±1.7) years. Oligoarticular JIA was present in 92.8% of patients and anterior uveitis in 96%. The most common ocular complications recorded in our sample were posterior synechiae (37.6%), cataract (20.8%), band keratopathy (19.2%), glaucoma (7.2%), and macular edema (5.6%). Conventional immunosuppressants were used in 75.2% of patients with a mean duration of 9.1 years (±5.4), while biologics were administered in 47.2% of them for a period of 5.4 years. Adverse events (AE) were seen in 23% of patients being treated with Methotrexate, in 10.4% of patients treated with Adalimumab, in 38.5% of patients in therapy with Infliximab, and in 14.3% of patients being treated with Tocilizumab. No AE were reported in patients treated with Golimumab, Certolizumab, Abatacept and Rituximab.Conclusions: An aggressive treatment approach for patients with JIA-associated uveitis ensured a low number of ocular complications with a good safety profile.

ObjectivesTo define the correlation between joint ultrasonography and clinical examination in patients with juvenile idiopathic arthritis (JIA) and to assess whether synovitis detected by ultrasonography in clinically inactive patients predicts arthritis flares.Methods88 consecutive patients with JIA—46 (52%) with persistent oligoarthritis, 15 (17%) with extended oligoarthritis, 15 (17%) with rheumatoid factor-negative polyarthritis and 12 (14%) with other forms of JIA, all clinically inactive for a minimum of 3 months—underwent ultrasound (US) assessment of 44 joints. Joints were scanned at study entry for synovial hyperplasia, joint effusion and power Doppler (PD) signal. Patients were followed clinically for 4 years.ResultsUS was abnormal in 20/88 (22.7%) patients and in 38/3872 (0.98%) joints. Extended oligoarthritis and rheumatoid factor-negative polyarthritis were more frequent in US-positive than in US-negative patients (35.0% vs 11.8% and 30.0% vs 13.2%, respectively; P=0.005). During 4 years of follow-up, 41/88 (46.6%) patients displayed a flare; 26/68 (38.2%) were US-negative and 15/20 (75%) were US-positive at baseline. Abnormality on US examination, after correction for therapy modification, significantly increased the risk of flare (OR=3.8, 95% CI 1.2 to 11.5). The combination of grey scale and PD abnormalities displayed a much higher predictive value of relapse (65%, 13/20) than grey scale alone (33%, 6/18).ConclusionsUS abnormalities are a strong predictor of relapse at individual patient level. Irrespective of treatment, the risk of flare in US-positive versus US-negative patients was almost four times higher. In case of US abnormalities, patients should be carefully followed regardless of both the International League of Associations for Rheumatology and Wallace categories.

Objective. To evaluate the efficacy and safety of a chimeric monoclonal anti-tumor necrosis factor ␣ antibody (infliximab) with methotrexate (MTX) in juvenile idiopathic arthritis (JIA) with an active polyarticular course that is not responsive to MTX.Methods. Twenty-four young adults with longlasting, refractory JIA were enrolled in an open, prospective, 2-year pilot study. Patients received intravenous infliximab at 3 mg/kg of body weight at weeks 0, 2, and 6 and every 8 weeks thereafter, with weekly subcutaneous MTX.Results. The median duration of therapy was 9.1 months. Significant improvements were observed in the number of joints (28-joint count) with active disease (median 6 at baseline, 2 at 2 weeks, 0 at 6 months, 0 at 1 year; P < 0.05). Pain as well as patient's and physician's global assessments of disease status were assessed on 0-100-mm (0 ‫؍‬ best; 100 ‫؍‬ worst) visual analog scales (VAS). There were significant improvements in VAS pain scores (45 at baseline, 25 at 2 weeks, 8.5 at 6 months, 10 at 1 year; P < 0.05), patient's global assessment of disease status (50 at baseline, 22 at 2 weeks, 11.5 at 6 months, 18 at 1 year; P < 0.05), and physician's global assessment of disease status (50.5 at baseline, 22.5 at 2 weeks, 6.5 at 6 months, 10 at 1 year; P < 0.01). In addition, there were significant improvements in the erythrocyte sedimentation rate (64 mm/ hour at baseline, 36 mm/hour at 2 weeks, 23.5 mm/hour at 6 months, 35 mm/hour at 1 year; P < 0.01) and C-reactive protein level (4.9 mg/dl at baseline, 2.8 mg/dl at 2 weeks, 3.1 mg/dl at 6 months, 3.2 mg/dl at 1 year; P < 0.005). The percentage of patients meeting the American College of Rheumatology 20% improvement criteria at each assessment ranged from 54.2% to 86.7%. Of the responses on the Disease Activity Score in 28 joints, 37.5-63.6% were classified as "good," 14.3-33.3% were classified as "moderate," and 18-37.5% were classified as "no response." Twelve patients (50%) had adverse events, and 5 patients (20.8%) withdrew.Conclusion. Infliximab plus MTX showed high effectiveness and safety in short-and medium-term treatment of long-lasting refractory JIA. A controlled multicenter clinical trial is needed.

Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases in children. Recently, the management of JIA has substantially changed, thanks to the availability of new treatment options, represented by biological drugs or biologics. These drugs modulate specific mechanisms of the immune systems, such as TNF-α, IL-1 and IL-6 signaling, or lymphocyte activation and/or functioning. In this review, we provide a comprehensive discussion on the current recommendations and clinical evidences regarding the use of the available biologics in the treatment of JIA; moreover, the main pharmacokinetic and pharmacodynamic aspects of any specific biologic drug have been summarized.