Etanercept in systemic juvenile idiopathic arthritis

OBJECTIVE: To evaluate the effectiveness of etanercept in patients with systemic juvenile idiopathic arthritis (SJIA) refractory to methotrexate (MTX) therapy in a pediatric rheumatology practice. METHODS: Fifteen patients with SJIA with active polyarthritis refractory to higher dose MTX (> or = 20 mg/m2/week) for at least 3 months were included. Patients received etanercept 0.4 mg/Kg twice weekly concomitantly with MTX. Observed period of treatment ranged from 5 to 12 months (median 9 months). RESULTS: Improvement of ESR, swollen and limited joint counts, functional capacity, and general wellbeing was achieved by 14/15 patients. The most significant impact on these variables was observed 3 to 5 months after treatment onset. Mean time to improvement was 2 months. In the 4 patients who presented fever and rash, these signs disappeared after the beginning of etanercept treatment and reappeared during flares. Three patients showed sustained clinical and biochemical remission on low dose MTX (< or = 5 mg/m2/week). Thirteen relapses were observed in 9 (60%) patients at a mean of 7.6 months after therapy was begun. Etanercept was discontinued due to lack of efficacy in 7 patients, only after higher dose (1 mg/kg/dose) was used. MTX and corticosteroid doses were decreased during the observation period. No serious side effects were observed. CONCLUSIONS: Etanercept, in combination with MTX, demonstrated benefit soon after initiation of treatment in patients with refractory SJIA, but flares and progressive loss of effectiveness were observed with continued treatment in most patients. Sharp decreases in the dose of MTX and corticosteroids may have contributed to subsequent occurrence of flares. Changes in MTX and corticosteroids doses should probably need to be made gradually, and it is possible that patients on SJIA should continue on therapeutic doses of MTX while being on etanercept in order to maintain therapeutic benefit.     

Etanercept and uveitis in patients with juvenile idiopathic arthritis

OBJECTIVES: Etanercept has been shown to be effective for the treatment of juvenile idiopathic arthritis (JIA). The therapeutic efficacy of etanercept for chronic uveitis, a major complication of JIA, has not been evaluated so far. Therefore, the appearance of chronic anterior uveitis and associated complications in JIA patients treated with etanercept was evaluated. METHODS: Questionnaires were sent to paediatric rheumatologists treating a total of 310 JIA patients with etanercept. RESULTS: Two hundred and twenty-nine questionnaires (74%) were returned. Before institution of etanercept, 31 patients (13.5%) had a history of uveitis with a total of 102 flares. Twenty-eight patients belonged to the high-risk groups of the oligoarticular and seronegative polyarticular subtypes. Upon commencing etanercept, 32 courses of uveitis occurred in 19 patients and in two further patients (1%) in whom uveitis occurred for the first time. Twenty of them belonged to the high-risk group. Uveitis during etanercept therapy occurred in 12 of 15 patients (80%) with more than one course of uveitis, and in seven of 16 patients (44%) with only one course before etanercept therapy. Complications were noted in 12 patients before and in eight during etanercept treatment. In 87% of the uveitis patients, arthritis demonstrated a significant or complete response. CONCLUSION: During treatment with etanercept, there were both relapses and first courses of uveitis. In addition, the frequency and severity of uveitis seemed not to be influenced by etanercept. In particular, patients with relapsing uveitis before institution of etanercept treatment remain at high risk of the development of uveitis flares despite etanercept treatment.     

Etanercept and urticaria in patients with juvenile idiopathic arthritis

Etanercept, a tumor necrosis factor receptor p75 Fc fusion protein (TNFR:Fc; Enbrel), has preliminarily been shown to be effective in the management of methotrexate-resistant polyarticular juvenile idiopathic arthritis (JIA). Reported side-effects have been minor, for example injection site reactions and upper respiratory tract infections, not necessitating discontinuation of the medication (1, 2). We report on 2 patients who developed an urticaria-like rash with prurigo appearing bilaterally on the extensor surfaces of the elbows subsequent to etanercept injections.     

Safety and efficacy of once-weekly application of Etanercept in children with juvenile idiopathic arthritis

Etanercept—a recombinant TNF receptor fusion protein—has been approved for the treatment of resistant polyarticular juvenile idiopathic arthritis. In children with JIA, 0.4 mg/kg is given subcutaneously twice weekly. In adult patients efficacy and safety of etanercept, 25 mg twice weekly was comparable to 50 mg once weekly. In the German paediatric Etanercept registry six patients with JIA were identified, who received Etanercept once weekly primarily and six patients who received Etanercept initially twice weekly and later once weekly with increased dose per injection. In both groups, treatment was efficacious and well tolerated. In patients switching from twice to once weekly administration, there was no loss of efficacy and no increase in toxicity. At last observation 10/12 patients achieved an ACR-JRA 30 and 8/12 achieved an ACR-JRA70 response. These data indicate that once weekly application of etanercept is safe and efficacous in children.     

Facioskeletal changes in children with juvenile idiopathic arthritis

OBJECTIVE: To investigate the facioskeletal morphology in patients with juvenile idiopathic arthritis (JIA) with and without temporomandibular joint (TMJ) involvement. METHODS: Eighty five patients were included. TMJ involvement was defined by orthopantomogram alterations. Lateral cephalograms were used to determine linear and angular measurements and occlusion. RESULTS: Patients regardless of their TMJ status had a 67% chance for retrognathia and a 52% chance for posterior rotation of the mandible and, respectively, 82% and 58% if TMJ involvement were present. Changes were not uniformly distributed among the different subtypes. CONCLUSION: Patients with JIA have an altered facial morphology, especially in the presence of TMJ involvement.     

Gower's sign in children with juvenile idiopathic arthritis

SIR, One clinical sign assessing proximal leg muscle weaknessis Gower's sign, the most important feature of which is theadoption of a prone position before standing. This can be seenduring normal development in toddlers up to the age of 36 months;only 6.5% of healthy children over 3 yr still roll prone duringstanding, while children with neuromuscular disorders have apositive early Gower's sign that persists after the age of 3yr [1]. Previous research in our     

Etanercept treatment in patients with refractory systemic onset juvenile rheumatoid arthritis

OBJECTIVE:. To assess the efficacy and safety of etanercept in a large cohort of children with refractory systemic onset juvenile rheumatoid arthritis (SOJRA). METHODS: Standardized questionnaires were sent to US pediatric rheumatologists about patients with SOJRA treated with etanercept. Data were collected at baseline and at the last visit on etanercept. Response to treatment was assessed and compared to baseline as the mean percentage reduction in the following: acute phase reactants, prednisone dose, active joint count, and physician global assessment of disease activity. Response was defined as poor if the mean reduction was < 30%, fair if 30% to < 50%, good if 50% to < 70%, and excellent if > 70%. RESULTS: We analyzed data obtained by survey of 82 SOJRA patients treated with etanercept for a mean of 25 months. Poor response to treatment was observed in 45% of the children, fair response in 9%, good in 13%, and excellent in 33%. Baseline steroid therapy could be discontinued in 27/59 (46%) patients. One or more disease flares occurred in 45% of all patients. Twenty-nine patients (35%) discontinued therapy, mostly due to lack of response or flare. There were 32 adverse event reports, most not considered serious, except for 2 cases of macrophage activation syndrome. CONCLUSION: In this cohort of children with SOJRA, 46% had a good or excellent response, and most were able to reduce concomitant corticosteroid doses. The response to etanercept was fair or poor in more than half our study population, and disease flares were common. Due to the unique cytokine profile of SOJRA, tumor necrosis factor blockade may not be the optimal therapeutic approach for children with treatment-resistant SOJRA.     

Effects on growth and body composition of growth hormone treatment in children with juvenile idiopathic arthritis requiring steroid therapy

OBJECTIVE: Decreased growth velocity and abnormal body composition including severe osteoporosis are common in glucocorticoid-treated patients with juvenile idiopathic arthritis (JIA). We evaluated the effects of recombinant human growth hormone (GH) given for 3 years on growth velocity, height standard deviation score (SDS), and body composition, together with potential adverse effects on glucose tolerance. METHODS: Thirteen patients received GH (0.46 mg/kg/week) for 3 years. Body composition was assessed by dual-energy x-ray absorptiometry and glucose tolerance by annual oral glucose tolerance tests. RESULTS: Median growth velocity increased from 2.1 to 6.0 cm/year (p = 0.002) in the first year and remained higher than baseline in the second year of treatment. Height SDS did not change significantly (-4.6 SDS at baseline vs -4.3 SDS at study completion), but the growth response varied markedly across patients. Compared with baseline, lean mass increased by 33%, fat mass remained stable, and lumbar bone mineral density increased by 36.6%. Transient glucose intolerance developed in 6 patients, but glycosylated hemoglobin concentrations did not change significantly and diabetes mellitus did not occur. CONCLUSION: Treatment with GH restored linear growth without inducing catch-up growth, significantly improved body composition, and prevented further bone loss. Prolonged followup is needed to assess the benefits of GH and longterm consequences of hyperinsulinism.     

Oral health of children with juvenile idiopathic arthritis

OBJECTIVE:s. To estimate dental disease indices and temporomandibular joint (TMJ) dysfunction in children with juvenile idiopathic arthritis (JIA). METHODS: Indices were recorded for dental caries, bacterial dental plaque, gingival inflammation, and TMJ dysfunction in children with JIA and matched controls. RESULTS: There was no significant difference in dental caries experience or the mean plaque score between children with JIA and controls. The mean gingivitis score for the permanent teeth only was significantly greater in the JIA children compared with the controls (p = 0.02). There was a significantly greater proportion of children with JIA with signs of both left and right TMJ dysfunction (p = 0.05, p = 0.02) and symptoms (p = 0.0001, p = 0.0001) compared with controls. CONCLUSION: The low caries rate was attributed to the fact that children with JIA had received preventive dental care from an early age combined with sugar free medication.     

Clinical analysis in 202 children with juvenile idiopathic arthritis

This study attempts to characterize the clinical features of various subtypes of juvenile idiopathic arthritis (JIA) and try to investigate the prognostic factors. Patients with JIA hospitalized in Nanjing Children Hospital during April 2005 to April 2010 were enrolled. Clinical manifestations and laboratory parameters were retrospectively reviewed. A total of 202 cases were included, 105 males and 97 females, with average age at onset of 7.5 years. Patients with systemic JIA were most common, accounting for 47.0 %. Fever, rash, and arthritis were the most common clinical manifestations. The most commonly involved joints were the knee and ankle. Laboratory parameters were significantly different but not specific. Time from onset to treatment, hepatomegaly, and involvement of wrist may have a significant effect on the outcome. A total of 117 cases were followed up, with an average follow-up time of 2 years. Among them, 55 cases achieved complete remission, 27 cases with partial remission, and 29 cases without remission, and six died. JIA is a heterogeneous disease with varied onset and clinical manifestations, which makes treatment a serious challenge. Receiving treatment late, hepatomegaly, and impaired wrist were early risk factors for an unfavorable outcome.     

Hepatitis B vaccination in children with juvenile idiopathic arthritis

OBJECTIVES: To evaluate the responsiveness of children with juvenile idiopathic arthritis (JIA) to hepatitis B vaccination and to determine the most useful vaccination schedule. METHODS: 39 children with JIA were enrolled in the study; all were in remission and negative to serological testing for hepatitis B surface antigen (HbsAg). The control group consisted of 41 healthy children. There were two different vaccination schedules: group I was vaccinated at 0, 1, and 3 months; group II was vaccinated at 0, 1, and 6 months. Positive responsiveness to the vaccine was defined as an anti-hepatitis B antibody titre above 10 mIU/ml. RESULTS: All the children except one with systemic JIA developed an antibody response. None of the JIA patients experienced a flare up or clinical deterioration related to the vaccination. The antibody levels in children with JIA were significantly lower than in the healthy controls. Comparison of the antibody levels between the two vaccination schedules showed no statistical difference in the controls; in the JIA subjects the group II schedule resulted in a trend to a greater response than the group I schedule (p<0.07). Vaccine responsiveness was not influenced by either methotrexate or prednisolone treatment. CONCLUSIONS: Children with JIA had an adequate response to hepatitis B vaccination and the response was not affected by immunosuppressive treatment. A vaccination schedule at 0, 1, and 6 months seems to be preferable to 0, 1, and 3 months.     

Preferential immunoglobulin oxidation in children with juvenile idiopathic arthritis

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a rare chronic inflammatory disorder of the joints. There is strong evidence that oxidative damage occurs in rheumatoid diseases, including JIA. The increased level of protein oxidation products in total plasma proteins has recently been reported in children with diagnosed JIA. The objective of this study was to find out which fraction of plasma proteins is mostly damaged by oxidative stress and whether the damaging effect correlates with certain clinical or laboratory parameters. METHODS: A new approach to estimate the carbonyl content of plasma protein fractions was developed, based on two-stage electrophoresis and immunochemical detection of the carbonyl derivatives of the proteins. This method allowed us to detect and quantitate carbonyl groups in the albumin, alpha-2, beta and gamma-globulin fractions. Sera of 25 children with JIA and 13 healthy controls were tested. RESULTS: Albumin and gamma-globulins were found to be most modified by oxidation. In a group of children with systemic JIA, both albumin and gamma-globulins were oxidized while plasma gamma-globulin fraction damage was prevalent in pauciarticular JIA. CONCLUSIONS: Among plasma proteins of children with JIA, gamma-globulins were preferentially oxidized, whereas most of the other proteins did not seem to be affected. Oxidative modification of plasma proteins was correlated with the type of JIA. These findings may allow the use of carbonyls as clinical markers of inflammatory process activity in patients with different types of JIA. It is also a potential tool for monitoring oxidative protein damage in other diseases and therapies.