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ObjectivesTo evaluate the long-term efficacy and safety of canakinumab in patients with active systemic juvenile idiopathic arthritis (JIA).MethodsPatients (2–19 years) entered two phase III studies and continued in the long-term extension (LTE) study. Efficacy assessments were performed every 3 months, including adapted JIA American College of Rheumatology (aJIA-ACR) criteria, Juvenile Arthritis Disease Activity Score (JADAS) and ACR clinical remission on medication criteria (CRACR). Efficacy analyses are reported as per the intent-to-treat population.Results144 of the 177 patients (81%) enrolled in the core study entered the LTE. Overall, 75 patients (42%) completed and 102 (58%) discontinued mainly for inefficacy (63/102, 62%), with higher discontinuation rates noted in the late responders group (n=25/31, 81%) versus early responders (n=11/38, 29%). At 2 years, aJIA-ACR 50/70/90 response rates were 62%, 61% and 54%, respectively. CRACR was achieved by 20% of patients at month 6; 32% at 2 years. A JADAS low disease activity score was achieved by 49% of patients at 2 years. Efficacy results were maintained up to 5 years. Of the 128/177 (72.3%) patients on glucocorticoids, 20 (15.6%) discontinued and 28 (22%) tapered to 0.150 mg/kg/day. Seven patients discontinued canakinumab due to CR. There were 13 macrophage activation syndrome (three previously reported) and no additional deaths (three previously reported). No new safety findings were observed.ConclusionResponse to canakinumab treatment was sustained and associated with substantial glucocorticoid dose reduction or discontinuation and a relatively low retention-on-treatment rate. No new safety findings were observed on long-term use of canakinumab.Trial registration numbersNCT00886769, NCT00889863, NCT00426218 and NCT00891046.

Objective To perform a retrospective study comparing clinical and laboratory aspects of patients with acute rheumatic fever (ARF) and patients with post-streptococcal reactive arthritis (PSRA), to discern whether these are 2 separate entities or varying clinical manifestations of the same disease. Study design We located the records of 68 patients with ARF and 159 patients with PSRA, whose diseases were diagnosed with standardized criteria and treated by 8 pediatric rheumatologists in 7 medical centers, using the Israeli internet-based pediatric rheumatology registry. The medical records of these patients were reviewed for demographic, clinical, and laboratory variables, and the data were compared and analyzed with univariate, multivariate, and discriminatory analysis. Results Four variables were found to differ significantly between ARF and PSRA and serve also as predictors: sedimentation rate, C-reactive protein, duration of joint symptoms after starting anti-inflammatory treatment, and relapse of joint symptoms after cessation of treatment. A discriminative equation was derived that enabled us to correctly classify >80% of the patients. Conclusion On the basis of simple clinical and laboratory variables, we were able to differentiate ARF from PSRA and correctly classify >80% of the patients. It appears that ARF and PSRA are distinct entities.

OBJECTIVE To evaluate the effect of disease severity and colchicine treatment on height and weight parameters in children with familial Mediterranean fever (FMF). METHODS Thirty prepubertal children (19 M, 11 F) were studied retrospectively. Z-score values of height, growth velocity, weight and body mass index were obtained over 1.84 +/- 1.14 years before and 2.58 +/- 1.55 years during colchicine therapy. Disease severity was evaluated by a specific score for FMF. RESULTS By comparison to growth before treatment, during colchicine therapy height SDS increased from -1.00 +/- 1.17 to -0.54 +/- 0.96 (p < 0.001) and weight SDS increased from -0.74 +/- 1.09 to -0.47 +/- 1.06 (p = 0.008). An effect of disease severity on growth pattern could not be detected. Height SDS during therapy was negatively correlated with age at colchicine initiation. CONCLUSIONS Colchicine therapy has a positive effect on both height and weight parameters in children with FMF. Early initiation of treatment is beneficial for height gain.

Ibuprofen is as effective as paracetamol (acetaminophen) as an antipyretic and analgesic agent in paediatric patients. Ibuprofen is considered to be well tolerated; however, there are reports on gastrointestinal bleeding or renal adverse effects among children treated with ibuprofen. Oral ibuprofen suspension was recently registered and approved by the Ministry of Health in Israel as an antipyretic and analgesic agent. Before distribution of the drug to pharmacies, we aimed to follow possible adverse effects among children receiving ibuprofen suspension in several paediatric wards and clinics. Children with fever needing antipyretic medication received ibuprofen oral suspension 5 to 10 mg/kg/dose. In each case the age of the patient, gender, diagnosis, number of ibuprofen doses, duration of treatment and any adverse reactions were reported. 1564 children from 14 paediatric wards (11 hospitals) and from five paediatric and family clinics participated in the study; 882 males and 682 females. The patients, aged 3.6 ± 4.2 years (range 1 month to 16.5 years), received 2.4 ± 3 (range 1 to 22) doses of ibuprofen suspension for 1.56 ± 2.11 (range 1 to 20) days. Adverse reactions were reported among 26 patients (1.66%) [95% confidence interval (CI) 1.1–2.4]; 18 children (1.15%) [95% CI 0.7–1.8] vomited immediately after the administration of the drug and it was not readministered. Two children (0.12%) [95% CI 0.02–0.46] had abdominal pain that resolved spontaneously, two patients reported nausea, and two other children had diarrhoea. Eight children (0.51%) reported experiencing a ‘bitter taste’ from the medication, of whom one patient discontinued the medication while the other seven continued it. The adverse reactions following administration of oral ibuprofen suspension reported in our study were low in frequency, mild and disappeared spontaneously. However, continuing reporting on its tolerability is needed.

We performed a prospective, randomized, open-label equivalence study comparing the use of naproxen to aspirin in 33 patients with rheumatic fever. The mean time until resolution of arthritis was 2.9+/-2.9 days in both groups. Liver enzyme elevations were more frequent in the aspirin group (P=.002). We conclude that naproxen is as effective, is easier to use, and is safer than aspirin in the treatment of the arthritis of rheumatic fever.

There is a debate whether post-streptococcal reactive arthritis (PSRA) is a separate entity or a condition on the spectrum of acute rheumatic fever (ARF). We believe that PSRA is a distinct entity and in this paper we review the substantial differences between PSRA and ARF. We show how the demographic, clinical, genetic and treatment characteristics of PSRA differ from ARF. We review diagnostic criteria and regression formulas that attempt to classify patients with PSRA as opposed to ARF. The important implication of these findings may relate to the issue of prophylactic antibiotics after PSRA. However, future trials will be necessary to conclusively answer that question.

To obtain longitudinal data on growth/puberty in a large-scale, multi-national prospective cohort of juvenile systemic lupus erythematosus (SLE).Data from 331/557 (59.4%) patients ≤18 years old with juvenile SLE in active phase, with anthropometric data available at four follow-up visits, were studied.There was a significant reduction in parent-adjusted height z score with time in females and males (p0.0001), with a significant gender difference (p0.0001) and with male height being most affected. Median body mass index z score peaked at 6 months and was still significantly above baseline after 26 months (p0.01), with no gender difference. Standardised height reduction was inversely related to age at onset. Females with onset age12 years had a median parent-adjusted height z score of -0.87 with no catch-up growth. At the end of the study, growth failure was seen in 14.7% of the females and 24.5% of the males. Height deflection (less than -0.25/year) was found in 20.7% of the females and 45.5% of the males. Delayed pubertal onset was seen in 15.3% and 24% of the females and males, respectively, and delayed/absent menarche was seen in 21.9%, while 36.1% of the females and 44% of the males had some degree of delayed pubertal development. Growth failure baseline determinants were previous growth failure (OR: 56.6), age at first visit ≤13.4 years (OR: 4.2) and cumulative steroid dose426 mg/kg (OR: 3.6).The children at risk of having a negative effect on height and pubertal development are prepubertal and peripubertal children treated with400 mg/kg cumulative dose of corticosteroids.

Introduction Juvenile idiopathic arthritis (JIA) is defined as onset of disease at 16 years of age, with arthritis persisting in 1 joint for at least 6 weeks and with active exclusion of other well-defined diseases such as systemic lupus erythematosus, etc. JIA is a heterogeneous group of arthritides with diverse presentation, course, and outcome (1). The role of infection, particularly streptococcal infection, in the pathogenesis of autoimmune diseases has been studied in the past (2). There is some evidence that streptococcal infection may be a trigger or maintenance factor in the pathogenesis of juvenile dermatomyositis (DM) (3) and psoriasis (4). In this report, we describe a group of patients with JIA in whom streptococcal infection possibly caused a flare or worsening of their chronic disease.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of middle-sized arteries, found in both adults and children. Disease pathogenesis is poorly understood. We identified multiple cases of systemic PAN and cutaneous PAN in families and individuals of Georgian-Jewish ancestry, consistent with autosomal recessive inheritance. While most cases (17/20) had childhood onset, cutaneous PAN could also initiate in middle age.

Background Systemic juvenile idiopathic arthritis (SJIA) is a rare autoinflammatory disease. Phase 3 data showed canakinumab (CAN), a fully human selective anti-IL-1β monoclonal antibody, provided robust initial adapted ACRpedi response in SJIA patients (pts) following a single dose. Objectives Demonstrate sustained efficacy of CAN in the maintenance of adapted ACRpedi response. Methods This was a two-part Phase 3 study in SJIA pts (2-20 yrs; CAN naive or rolled-over from earlier studies). Part 1 (P1), an open label, active treatment maximum 33 wk long period (including a max 20 wk corticosteroid [CS] dose reduction subpart) was followed by Part 2 (P2), a randomized, DB, placebo-controlled, event-driven period. In P1, pts received CAN sc (4mg/kg to 300mg max) every 4 wks. Primary endpoint for P1 was the proportion of pts on CS at study entry who were able to taper it. We present data for the secondary endpoints: maintenance of adapted ACRpedi30/50/70/90/100 criteria, number of active joints and physician’s global assessment of disease activity (PGDA; 0-100 mm VAS) during P1. ACR response was assessed at Days 15, 29 and every 4 weeks thereafter. PGDA and number of active joints were assessed at these same visits and at Baseline (BL) and Day 3. Results 177 pts (128 on CS; 49 steroid-free) entered P1, of which 100 pts (CAN, n=50; placebo, n=50) entered P2; most of the 77 pts who did not enter P2 were eligible (>ACR30 at Day 15) to enter an open-label extension study directly when they discontinued. Of 92 pts attempting CS taper according to pre-specified criteria, 57 (62%) were successful, representing 44.5% (57/128; p Conclusions CAN allowed for successful steroid tapering with sustained maintenance of high adapted ACRpedi response while demonstrating an acceptable safety and tolerability profile in pts with active SJIA. Disclosure of Interest P. Quartier Grant/Research support from: Novartis, J. Anton Grant/Research support from: Novartis, Pfizer, Consultant for: Novartis, Roche, Paid Instructor for: Novartis, Roche, Abbot, Speakers Bureau: Novartis, Pfizer, Abbot, SOBI, J. Barash Grant/Research support from: Novartis, R. Berner Grant/Research support from: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, D. Kim Shareholder of: Novartis, Employee of: Novartis, N. Wulffraat: None Declared

In different from rheumatic fever (RF), the association of post streptococcal reactive arthritis (PSRA) and carditis is controversial. Currently the American Heart Association recommends anti-streptococcal prophylaxis for PSRA for one year, repeat echocardiogram and discontinuation of prophylaxis if normal (level 2, C evidence).

Canakinumab (CAN), a selective, human, anti- interleukin-1β monoclonal antibody, has been shown to be efficacious in the treatment of SJIA (Ruperto et al. N Engl J Med 2012).