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ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

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...

JAK-inhibitors are small molecules blocking the JAK-STAT pathway that have proven effective in the treatment of different immune-mediated diseases in adults and juvenile idiopathic arthritis (JIA).Aim of StudyTo evaluate the safety and efficacy of tofacitinib in children with different rheumatic diseases.Material and MethodsWe extracted information from 24 children with the following diagnosis: JIA (n = 15), undifferentiated systemic autoinflammatory diseases (SAIDs) (n = 7), and juvenile dermatomyositis (JDM) (n = 2) who have been treated with tofacitinib for a period of longer than 6 months. The treatment outcomes were classified according to the opinion of the attending physicians as having a complete response (CR), i.e., the absence of disease activity, or a partial response (PR)—a significant improvement of symptoms and disease activity, or no response (NR)—no changes in disease activity.ResultsCR was achieved in 10/24 patients; 7/15 among JIA patients, 1/2 among JDM patients, 4/7 among SAID patients, and PR in 5/15 of JIA, 1/2 of JDM, and 3/7 of SAID patients. Three non-responders with JIA discontinued tofacitinib. Corticosteroids were successfully tapered off in 11/14 patients and discontinued in 2/14 patients. Four patients had side effects not requiring treatment discontinuation: liver enzyme elevation (n = 2), hypercholesterolemia (n = 1), lymphadenitis (n = 1).ConclusionJAK-inhibitors are effective new therapies for the treatment of multiple immune-mediated diseases. Our experience has shown the best results in patients with JIA and JIA-associated alopecia, and type I interferonopathies. More data from randomized controlled clinical trials are needed to use JAK-inhibitors safely in pediatric rheumatic diseases.