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Objective To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. Methods The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. Results A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach’s alpha 0.64–0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04–2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still’s disease. Conclusion The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

BackgroundSystemic juvenile idiopathic arthritis (SoJIA) is the most striking form of juvenile idiopathic arthritis. The aim of our study was to evaluate the clinical responses and outcomes of children with SoJIA to IL-6 blockade using two different tocilizumab (TCZ) treatment protocols designed for milder and more severe SoJIA patient groups, and evaluate the possibility of achieving biologic-free remission.MethodsThirty-seven active SoJIA children who have failed treatment with corticosteroids and other DMARDs were included in our retrospective study. TCZ doses were prescribed in two treatment approaches: every 2 weeks TCZ dosing (Q2W) and every 4 weeks TCZ dosing (Q4W). The patients were assigned to these two groups by the study physicians depending on the severity of the SoJIA disease as judged by each clinician.ResultsThirty-three of the 37 children successfully completed the trial. TCZ was discontinued in 11patients during the trial. Seven children achieved inactive disease and were allowed to stop the TCZ and 4 had severe adverse events requiring drug cessation. Currently 7 patients continue to have TCZ-free remission [4/7 remission off-medication, 3/7still on methotrexate (MTX)]. This mixed group had a median treatment duration of 1002 days. The children in remission off of all medications, TCZ and MTX, had a median remission duration of 1162 days (ranged 932–1301 days).Compared to the patients assigned to the Q2W TCZ treatment group, the patients assigned to the Q4W TCZ group had a milder SoJIA course. The patients had higher levels of hemoglobin, total proteins, and serum albumins. They had lower white blood cell counts (WBC), % granulocytes, CRP, ESR, ferritins, and LDH. These children had a lower frequency of internal organ involvement, fewer relapses during TCZ treatment, and no macrophage activation syndrome episodes.ConclusionsOur experience with TCZ for SoJIA supports the excellent result of other studies. What may be novel is our finding that thisIL-6 blockade with TCZ may be able to be utilized at a less frequent dosing schedule in mild SoJIA compared to severe SoJIA. We discuss other factors that may increase the probability of a patient reaching TCZ-free remission.

BackgroundUveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA), often entirely asymptomatic but could be sight-threatening. The main predictors of uveitis in JIA are oligoarticular (OA) subtype, ANA-positivity and younger age at the JIA onset. Methotrexate (MTX) has been able to decrease the incidence of uveitis in JIA up to 2 times [1]. Treatment of JIA depends on number of active joints: NSAID and intra-articular (IAC) steroid injection are the first line-therapy for OA subtype of JIA. In Russia there is a restricted access to prolonged intra-articular steroids, such as triamcinolone hexacetamide. In the cases of relapse after short-term IAC followed by start of MTX therapy, which lead to higher proportion of patients with JIA, treated with MTX then in Europe and North America.ObjectivesTo re-evaluate the possibility of MTX to prevent the onset of uveitis in Russian JIA cohort patients with increased proportion of applying of MTX.MethodsThe clinical charts of all consecutive patients who had received a stable management for at least 2 years with or without MTX were reviewed. Patients who were given systemic medications other than MTX (except NSAID) were excluded. Patients with systemic arthritis, rheumatoid factor-positive arthritis, or enthesitis-related arthritis were also excluded. In each patient, the al least 2-year follow-up period after first visit was examined to establish whether uveitis had occurred.ResultsA total of 281 patients with a median disease duration of 3.8 year were included. One hundred and ninety one patients (68%) were treated with MTX compare to 33.9% in previous study [1]. During the at least 2-year follow-up, 64 patients (22.8%) developed uveitis, a median of 1.6 year after the disease onset. The frequency of uveitis was lower in MTX-treated than in MTX-untreated patients (11.5% vs 46.7%, respectively, OR=6.7 (95%CI:3.7-12.3), p=0.0000001). In previous study the frequency of uveitis was 10.5 in MTX-treated vs 20.2 in MTX-untreated patients [1]. Survival analysis confirmed that patients treated with MTX had a lower probability of developing uveitis (HR=4.35, p=0.000001) (Fig.). In subgroup analysis was shown that MTX more preventive in boys (HR=6.7, p=0.0007) than in girls (HR=3.6, p=0.000001); in patient with onset age more than 5 years (HR=22.2, p=0.000001) than whom disease onset less 5 years (HR=2.3, p=0.003). The data of survival analysis of MTX prevention not shown benefits depend on number of active joints: in OA (HR=4.0, p=0.000001) similar to polyarthritis (HR=3.7, p=0.02) and ANA status: ANA-positive (HR=4.4, p=0.00002) similar to ANA-negative (HR=3.6, p=0.003).ConclusionsMTX therapy may prevent the onset of uveitis in children with JIA. Further randomized controlled trial required to confirmation our results.ReferencesPapadopoulou C, Kostik M, Bohm M, Nieto-Gonzalez JC, Gonzalez-Fernandez MI, Pistorio A, Martini A, Ravelli A. Methotrexate Therapy May Prevent the Onset of Uveitis in Juvenile Idiopathic Arthritis. J Pediatr 2013;163:87...

Chronic non-bacterial osteomyelitis (CNO) is a chronic inflammatory bone disease which usually manifests in children and adolescents. There are a few data about pathogenesis and treatment. The aim of the study to compare the efficacy of different treatment approaches in pediatric CNO cohort patient. Fifty two children (25 boys and 27 girls) with CNO with average age at the onset of the disease 8.4 years (5.4; 11.0), number of foci - 3.0 (2.0; 6.0, incl. multifocal cases in 80.8%). Non-steroid anti-inflammatory drugs (NSAID) was the first-line treatment for non-vertebral cases, as well as pamidronate (PAM) for vertebral involvement. Second-line treatment includes sulfasalazine (SSZ), methotrexate (MTX), PAM and tumor necrosis factor-α inhibitors (TNFα-inh). We evaluated the dynamics of pain, patient's and physician's (MDVAS) assessment with visual-analog scale (VAS) and ability to each medication to achieve remission of CNO activity. According to the NSAID, MTX, SSZ, PAM and TNFα-inh groups the following data were registered: patient's VAS: - 14.2% (p = 0.05), - 50.0% (p = 0.04), - 23.1 (p = 0.89), - 83.3% (p = 0.0001), - 73.6% (p = 0.0007); painVAS: - 21.9% (p = 0.01), - 18.6% (p = 0.13), + 36.4 (p = 0.89), - 79.7% (p = 0.00016), - 74.1%, (p = 0.0015); MDVAS: - 13.8% (p = 0.13); - 56.4% (p = 0.09), + 30.8% (p = 0.89), - 74.7%, (p = 0.0001), - 82.1 (p = 0.0015) respectively. The ability of each treatment strategy to achieve the CNO remission was 52.6%, 44.4%, 57,1%, 88.8% and 73.3%, respectively (log-rank test, p = 0.001). The efficacy of treatment approaches for CNO depended on the severity of the disease. NSAID, methotrexate, and sulfasalazine were effective in forms without spine involvement, but pamidronate and TNF-a inhibitors were useful in vertebral forms of CNO. Pamidronate and TNF-a inhibitors more extensively suppressed CNO activity. The randomized controlled trials for assessment of the efficacy and safety of these medications is mandatory to confirm these results.

The case of a 10-year-old boy with Farber lipogranulomatosis with predominant joint involvement, subacute, laryngeal and tongue granulomas, microcytic anemia, elevated ESR and CRP, is presented. The boy had no signs of CNS and internal organ involvement. The disease manifested at 6 months; at 11 months the boy had widespread granulomatous polyarthritis with contractures, and juvenile idiopathic arthritis (JIA) was suggested. All antirheumatic therapies failed. Immunologic assessment revealed elevated serum interleukin-1β, increased T-helper, NK and CD25-positive cells, and circulating immune complexes. Our case with predominant rheumatologic manifestations illustrates a differential diagnosis of JIA.

ObjectiveMacrophage activation syndrome (MAS) is a life-threatening, potentially fatal condition associated with systemic juvenile idiopathic arthritis (sJIA). Interleukin-1 (IL-1) is a key cytokine in the pathogenesis of sJIA MAS. Many cases of MAS are medically refractory to traditional doses of biologic cytokine inhibitors and may require increased dosing. When MAS occurs in the setting of sJIA treated with the IL-1 receptor antagonist (IL-1Ra), anakinra, increased anakinra dosing may be beneficial. Increased dosing of another IL-1 inhibitor, canakinumab, a monoclonal antibody to IL-1β, has not been reported to treat refractory MAS in the setting of sJIA.MethodsRetrospective data collection extracted from the electronic medical record focused on canakinumab usage and dosing in 8 children with sJIA who developed MAS at a single academic center from 2011 to 2020.ResultsEight sJIA children (five girls) with median age 8.5 years (range, 0.9–14.2 years) were included in the present study. Five children developed MAS at disease onset and three during ongoing canakinumab therapy. MAS resolved in all eight children with canakinumab treatment. When the canakinumab dosing was insufficient or MAS developed during canakinumab therapy, the dosing was temporally up-titrated (four patients, maximum 300 mg per dose) without observed side effects.ConclusionThis report provides evidence for the efficacy and safety of short-term increased doses (2–3-times normal) of canakinumab in treating sJIA associated MAS. Further study of the efficacy and safety of increased doses of canakinumab for treatment of MAS in children with sJIA is warranted.

Background.Etanercept is a biological drug most commonly used in patients with juvenile idiopathic arthritis (JIA). The results of its use are showed in local studies.Objective.Our aim was to evaluate the efficacy and safety of the use of etanercept in children with non-systemic JIA, to determine the predictors of remission and the risk factors for the development of exacerbations.Methods.In a retrospective cohort study, the results of etanercept treatment (remission, exacerbations, adverse events) in children with non-systemic JIA were analyzed. The minimum follow-up period was 6 months.Results.The period of remission within 6–36 months occurred in 77/131 (58.8%), exacerbations developed in 18/129 (14.0%) patients. Predictors of achieving remission were the age of JIA onset < 8 years [relative risk (RR) 2.05; 95% confidence interval (CI) 1.27–3.23], the age of prescribing etanercept ≤ 10 years (RR 1.7, 95% CI 1.22–2.38), the time of the disease prior to etanercept prescription < 2.5 years (RR 2.4, 95% CI 1.4–4.4), the presence of HLA-B27 antigen (RR 2.15, 95% CI 0.98–4.75; p = 0.06). The risk of exacerbations was higher in children with polyarticular JIA (RR 2.7, 95% CI 0.9–8.2; p = 0.08), whereas methotrexate therapy reduced the risk of exacerbations (RR 0.32, 95% CI 0.1–1.15; p = 0.05). Etanercept was discontinued due to primary (improvement by the ACRpedi criteria after 3 months of therapy <30%) or secondary (loss of previously achieved ≥ 30% improvement) failure in 14/152 (9.2%) patients; de novo uveitis developed in 8/152 (5.3%) patients; reactions at the injection site — in 6/152 (4.0%) patients.Conclusion.Therapy involving etanercept is more likely to induce remission in younger patients with JIA onset at the age of 8 years and a history of less than 2.5 years. A high risk of exacerbations was noted in patients with polyarticular JIA, and low one — in those receiving methotrexate as a part of combined therapy.