Clinical response to etanercept in polyarticular course juvenile rheumatoid arthritis

OBJECTIVE: To evaluate safety and clinical response to treatment with etanercept in the polyarticular course of patients with juvenile rheumatoid arthritis (JRA). METHODS: Ten patients were studied (8 female, 2 male; 6 polyarticular JRA, 4 systemic onset; mean age 13.3 yrs; mean duration of disease 6.6 yrs). Patients received 0.4 mg/kg etanercept subcutaneously twice weekly in addition to their existing therapeutic regimen. Observed duration of treatment ranged between 4 and 12 months. RESULTS: Patients tolerated treatment with etanercept well. No serious adverse events were noted. Treatment response showed considerable improvement of morning stiffness (mean reduction of 96 min approximately equal to -93%) and joint counts including swollen joints (delta -8.2 approximately equal to -40%), tender joints (delta -9.2 approximately equal to -88%), and total joints (delta -9.8 approximately equal to -37%). Laboratory results included decreases in ESR (delta -46 mm/h approximately equal to -53%) and improvement of anemia. CONCLUSION: Our results confirm etanercept is a powerful adjunct in the therapy of polyarticular JRA resistant to conventional treatment regimens.     

Pharmacokinetics,efficacy, and safety of short-term (12 weeks) etanercept for methotrexate-refractory polyarticular juvenile idiopathic arthritis in Japan

Abstract

We examined and evaluated the pharmacokinetics, efficacy, and safety of etanercept in patients with methotrexate (MTX)-refractory polyarticular juvenile idiopathic arthritis (JIA) in Japan. All MTX-refractory polyarticular JIA patients 4–17 years old received 0.4?mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to 3 months in the open-label, prospective, and multicenter trial. A response was defined as an improvement of 30%, 50%, 70%, or more from baseline in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30% from baseline (30%, 50%, or 70% definition of improvement, respectively), and disease activity score (DAS28) by EULAR (European League Against Rheumatism) response criteria. At the end of the 12-week study, 20 of the 22 patients (90.9%) had responses with both 30% and 50% definition of improvement after etanercept treatment. To our surprise, 15 of 22 patients (68.2%) had a response with 70% definition of improvement. Moreover, in DAS28, eight patients were evaluated as having a good response and there were no patients with a poor response to etanercept. Treatment had to be stopped in one patient who developed joint contracture during the study period, but there were no significant adverse events in the other patients. In conclusion, treatment with etanercept leads to significant improvement in patients with active polyarticular JIA in Japan. Etanercept is well tolerated by pediatric patients as well as adults.     

Pharmacokinetics, efficacy, and safety of short-term (12 weeks) etanercept for methotrexate-refractory polyarticular juvenile idiopathic arthritis in Japan

We examined and evaluated the pharmacokinetics, efficacy, and safety of etanercept in patients with methotrexate (MTX)-refractory polyarticular juvenile idiopathic arthritis (JIA) in Japan. All MTX-refractory polyarticular JIA patients 4–17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to 3 months in the open-label, prospective, and multicenter trial. A response was defined as an improvement of 30%, 50%, 70%, or more from baseline in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30% from baseline (30%, 50%, or 70% definition of improvement, respectively), and disease activity score (DAS28) by EULAR (European League Against Rheumatism) response criteria. At the end of the 12-week study, 20 of the 22 patients (90.9%) had responses with both 30% and 50% definition of improvement after etanercept treatment. To our surprise, 15 of 22 patients (68.2%) had a response with 70% definition of improvement. Moreover, in DAS28, eight patients were evaluated as having a good response and there were no patients with a poor response to etanercept. Treatment had to be stopped in one patient who developed joint contracture during the study period, but there were no significant adverse events in the other patients. In conclusion, treatment with etanercept leads to significant improvement in patients with active polyarticular JIA in Japan. Etanercept is well tolerated by pediatric patients as well as adults.     

Safety and efficacy of high dose etanercept in treatment of juvenile rheumatoid arthritis

OBJECTIVE: To evaluate safety and efficacy of high dose etanercept (> 0.8 mg/kg, maximum 25 mg subcutaneously twice weekly) (Enbrel) in children with juvenile rheumatoid arthritis (JRA) and inadequate prior response to standard dose etanercept. METHODS: Retrospective chart review of 8 children (6 girls, 2 boys, mean age 8.4 yrs, range 5-16 yrs). Five children had systemic onset, polyarticular course JRA; 2 had polyarticular onset; and one had pauciarticular onset, polyarticular course JRA. All children had failed at least 3 mo (mean 9 mo) treatment with standard dose etanercept (0.4 mg/kg SC twice a week). All 8 children had increase in the etanercept dose to at least 0.8 mg/kg (mean 1.1 mg/kg, maximum 25 mg SC twice weekly) for a mean of 7 mo (range 3-10 mo). Efficacy of high dose etanercept was evaluated by changes in joint count, laboratory data, and ability to decrease concomitant medication. RESULTS: Improvements in the joint count and laboratory findings (erythrocyte sedimentation rate, hemoglobin and platelet count) were observed in 2 of 8 (25%) children. In these 2, concomitant prednisone was reduced or discontinued. In contrast, no changes in disease activity or laboratory findings were observed in the other 6 children. Overall, high dose etanercept was well tolerated. No laboratory abnormalities were detected and no child withdrew because of adverse events. CONCLUSION: High dose etanercept is safe and well tolerated in children, but efficacy seems limited. In children with unsatisfactory response to standard dose etanercept, an increased dose or treatment prolongation may not offer any additional benefit.     

Safety and efficacy of etanercept in children with juvenile idiopathic arthritis below the age of 4 years

Little is known about the safety and efficacy of etanercept in children below the age of 4 years. Twenty-five patients with juvenile idiopathic arthritis (JIA) below the age of 4 years, who received etanercept, were documented in the German JIA Etanercept Registry. Patients with the nonsystemic JIA disease-subtype responded more frequently to treatment with etanercept than systemic onset patients. At last observation, two (20%) of the nonsystemic patients did not reach a PedACR 30 response, while six (40%) of the systemic onset patients did not respond to the therapy. Complete resolution of symptoms was observed in two (20%) nonsystemic and in five (33%) systemic onset patients with JIA. Tolerability was good with only two infections occurring in the total patients group. Patients with JIA below the age of 4 years, with a methotrexate-resistant disease course, would also benefit from treatment with etanercept, showing a good tolerability. The restriction to children older than 4 years appears to be artificial without any good rationale.     

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.     

Impact of anti-TNF treatment on growth in severe juvenile idiopathic arthritis

OBJECTIVES: To evaluate the impact of anti-tumour necrosis factor (TNF) treatment on growth and to identify the predictors for the change in growth in severe juvenile idiopathic arthritis (JIA). METHODS: Data from 71 JIA patients (43 on etanercept, 28 on infliximab) were reviewed two years before and two years on the anti-TNF treatment. The patients had polyarticular disease course (48 polyarthritis, 19 extended oligoarthritis, two systemic arthritis, and two enthesitis related arthritis). At the initiation of the anti-TNF treatment, their mean age was 9.6 years and the mean duration of JIA, 5.7 years. RESULTS: In the patients with delayed growth before anti-TNF treatment (n = 53), the growth velocity, measured as the change in height standard deviation score, accelerated +0.45 (95% confidence interval, 0.33 to 0.56) (p<0.001) during the anti-TNF treatment. In the patients with normal or accelerated growth before anti-TNF treatment (n = 18), the change in growth velocity was +0.05 (0.07 to 0.16) (p = 0.39). At two years on anti-TNF treatment, the growth velocity between these two groups was similar. No difference was found between the patients treated with etanercept or infliximab. A decelerating growth rate before the anti-TNF treatment was the strongest predictor for the observed increase in the growth velocity. The change in the inflammatory activity remained a significant predictor of the growth velocity even after the decrease in glucocorticoid dose was taken into account. CONCLUSIONS: In the treatment of polyarticular JIA, the anti-TNF treatment not only suppresses inflammation but also restores growth velocity.     

Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study

OBJECTIVE: To study infliximab and etanercept in the treatment of refractory juvenile idiopathic arthritis (JIA). METHODS: In a non-randomised, prospective, open label study, 24 patients (mean age 10.2 years, range 3.3-16.3) with polyarticular JIA were treated with either infliximab (n=14) or etanercept (n=10). The patients had had active polyarthritis for at least one year and standard treatment had failed. Anti-tumour necrosis factor (TNF) treatment was added to the current drug treatment. Infliximab (3-4 mg/kg) was given intravenously at weeks 0, 2, and 6, and thereafter at 4 to 8 week intervals. Etanercept (0.4 mg/kg) was given subcutaneously twice a week. Improvement of the patients was assessed at 3, 6, and 12 months according to established JIA response criteria. RESULTS: In intention to treat analyses, patients in both treatment groups improved significantly. ACR Paediatric 50 was achieved at 3, 6, and 12 months by 9/10 (90%), 8/9 (89%), and 8/9 (89%) patients with etanercept and by 8/12 (67%), 10/12 (83%), and 7/9 (78%) with infliximab, respectively. At 12 months, ACR Paediatric 75 was achieved by 67% of patients in both treatment groups. Five withdrawals due to adverse effects or lack of efficacy occurred in the infliximab group and one due to lack of compliance in the etanercept group. CONCLUSION: In this open label clinical study of active JIA, both infliximab and etanercept provided a significant rapid and sustained reduction in disease activity. Adequately powered randomised controlled trials are needed to elucidate the long term safety and efficacy of TNF modulators in the treatment of JIA.     

TNF and LT binding capacities in the plasma of arthritis patients: effect of etanercept treatment in juvenile idiopathic arthritis

BACKGROUND: Etanercept (Enbrel) induces a rapid and sustained decline in disease activity in the majority of patients with refractory juvenile idiopathic arthritis (JIA). For unknown reasons, however, a number of JIA patients fail to respond to this therapy. During this treatment neutralisation of tumour necrosis factor (TNF, previously termed TNF alpha) and lymphotoxin (LT, previously termed TNF beta) may be mediated by etanercept itself as well as by naturally occurring soluble TNF receptors. In light of this, it was of interest to study the total TNF neutralizing capacity in plasma before and during treatment with etanercept. RESULTS: In initial experiments plasma samples from healthy individuals were incubated with etanercept, and spiked with TNF or LT to a final concentration of 1000 pg/mL. Detection of TNF and LT by ELISA was found to be reduced by approximately 50% and 80% respectively, at a concentration of etanercept of 5-500 ng/mL, which is close to the pharmacological plasma concentrations. Plasma samples (n = 80) were then collected from 12 JIA patients (5 with pauciarticular, 5 with polyarticular and 2 with the systemic onset type) during treatment with etanercept (0.4 mg/kg twice weekly) for a period of 20.8 (15.6-23.9) months (median, range). The plasma samples were spiked with LT, and the inhibition of LT detection in ELISA was measured. In samples obtained 3 months after the start of etanercept, the inhibition of LT detection was augmented [72% (60-85)] compared with pre-treatment samples [16% (0.32)] (p = 0.0039). These findings were confirmed in binding assays using radiolabelled TNF. Among patients who responded insufficiently to therapy, reduced LT binding capacity, coinciding with flares of disease activity, was observed. CONCLUSION: We have developed an assay by which LT binding capacity, reflecting the level of free, pharmacologically active etanercept, may be monitored in the blood of patients treated with etanercept. This assay may prove to be useful in guiding dose adjustments in patients with an incomplete response to etanercept.     

Physical disability, articular, and extra-articular damage in patients with juvenile idiopathic arthritis

Data on outcome of juvenile idiopathic arthritis (JIA) from the Indian subcontinent is limited. Juvenile Arthritis Damage Index (JADI) is a newly proposed index which measures articular (JADI-A) and extra-articular damage (JADI-E). We studied the outcome of JIA using JADI in Indian patients. We assessed the damage in patients with JIA using JADI, and to see if JADI scores correlate with various parameters of damage and disease activity. We studied 89 patients of JIA (excluding enthesitis-related arthritis) with a >/=1-year duration of the disease. Besides JADI, clinical assessment included active joint count, joints with limited mobility, ESR, and CHAQ. Radiological damage was assessed according to the Dale scoring system. Correlation of JADI with various parameters was done by Spearman's rank correlation coefficient. The patient's distribution of JIA subtypes was polyarticular (47), systemic onset (SoJIA 23), oligoarticular (15), psoriatic arthritis (one) and others (three). The median duration of disease was 5 years (1-20). JADI-A ranged from 0-61 (Median 2); 60.7% of children had articular damage. Thirty-five (39.3%) patients had extra-articular damage; out of which, growth failure was the commonest. Persistent oligoarticular subtype had lesser JADI-A score as compared to SoJIA and polyarticular JIA. JADI-A correlated significantly with (p < 0.01) with radiological damage (0.538), CHAQ (0.567), JADI-E (0.513), duration of disease (0.385), and loss of education years due to disease (0.352). Further it also correlated with measures of disease activity like: ESR (0.286), duration of morning stiffness (0.258, p < 0.05), physician's global assessment (rS 0.623), and parent's global assessment (0.446), Almost two-thirds of patients with JIA had articular damage and one third had extra-articular damage. JADI is a good tool to measure damage in children with JIA.     

Temporomandibular involvement in juvenile idiopathic arthritis

OBJECTIVE: To study occurrence as well as clinical signs and symptoms of temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA) in a population representing all subtypes of JIA. METHODS: Ninety-seven consecutive children with JIA underwent orthodontic evaluation including an orthopantomogram (OPG). Further evaluation included patient characteristics, disease onset, course, and medical treatment. RESULTS: Forty-five percent of all children had TMJ involvement. Frequencies according to JIA subtypes: systemic 67%, oligoarticular (persistent and extended) 39%, rheumatoid factor (RF) negative polyarticular 59%, RF positive polyarticular 33%, enthesitis related arthritis 13%, psoriatic arthritis 33%, and other arthritis 50%. In children with a polyarticular course, irrespective of their disease onset, TMJ involvement was more frequent (55% vs 31% in oligoarticular course). In children with disease onset at a young age and/or an extended course of the disease, TMJ involvement was also more frequent. Pain during jaw excursion, absence of translation, asymmetry during maximal opening and protrusion, as well as crepitation during evaluation are predictors for TMJ involvement with a good specificity but a low sensitivity. Not all patients with TMJ involvement have clinical signs. CONCLUSION: Because of the high prevalence and discrepancy between clinical signs and presence of arthritis of the TMJ, regular orthodontic evaluation and OPG is recommended to recognize TMJ involvement and enable early intervention.     

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.     

The diagnostic value of anti-cyclic citrullinated peptide (CCP) antibodies in children with Juvenile Idiopathic Arthritis

BACKGROUND: Antibodies against cyclic citrullinated peptide (anti-CCP) are considered to be specific for rheumatoid arthritis (RA). OBJECTIVE: To assess the clinical significance of anti-CCP antibodies in a cohort of patients with juvenile idiopathic arthritis (JIA) and if they can be used to identify patients with an unfavourable course of disease. METHODS: 68 serum samples were investigated. 45 patients were diagnosed with JIA (15 male and 30 female) aged 1.9-17.3 years (median 12.9 mean 11,0). 5 patients had polyarticular (RF negative), 2 polyarticular (RF positive), 25 oligoarticular JIA, 6 enthesitis related arthritis, 2 psoriatric arthritis, 3 patients had systemic disease and 2 unclassified arthritis. 23 samples were taken from patients with non-inflammatory cardiac diseases undergoing interventional cardiac therapy. Enzyme-linked immunosorbent assay (ELISA; Euroimmun, Lübeck, Germany) was used for the detection and quantification of anti-CCP antibodies in patients with JIA. RESULTS: Overall, anti-CCP antibodies were found in 2.9% (2/68) of all samples and in 4.4 % (2/45) patients with JIA. CONCLUSION: Anti-CCP antibodies are associated with RF positive polyarticular course of JIA. Anti-CCP antibodies are not relevant for other subgroups of JIA. Therefore anti-CCP Abs in patients with JIA should not be investigated routinely.     

The German etanercept registry for treatment of juvenile idiopathic arthritis

OBJECTIVE: To describe a registry set up to monitor children treated with etanercept in Germany and Austria. METHODS: Giannini's criteria, duration of morning stiffness, number of swollen, tender and contracted joints, adverse events, and reasons for discontinuation were assessed. RESULTS: 322 patients with juvenile idiopathic arthritis (JIA) and 12 additional patients with non-JIA rheumatic diagnoses were included. Therapeutic efficacy was observed from one month after treatment was started. The number of patients with significant improvement and the degree of improvement increased during the first year. The mean (SD) number of tender and swollen joints decreased from 9 (9) and 8.4 (9) to 3.0 (6.5) and 4.5 (7) after one month, and to 2.2 (5.5) and 3.3 (5.5) after three months; morning stiffness decreased from 45 (65) minutes to 12 (30) and 7 (19) after one and three months (p<0.001 for all). Using Gianinni's criteria of 30%, 50%, and 70% improvement, a therapeutic response in JIA patients was achieved in, respectively, 66%, 54%, and 30% after one month, 78%, 61%, and 38% after three months, and 83%, 72%, and 52% after six months. Therapeutic efficacy was lower in patients with systemic onset arthritis. Overall tolerability was good: in 592 patient treatment-years there were 69 reports of adverse events in 56 patients, including one CNS demyelination. There were no opportunistic infections or lupus-like reactions. Treatment was discontinued in 53 JIA patients, in 25 because of lack of efficacy. CONCLUSION: Etanercept treatment was safe and led to a significant improvement in most JIA patients resistant to conventional 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.     

Long-term outcome and prognosis in oligoarticular-onset juvenile idiopathic arthritis

OBJECTIVE: To describe the long-term outcome and determine predictors of severity among patients with oligoarticular-onset juvenile idiopathic arthritis (JIA). METHODS: In a longitudinal study, 207 patients with oligoarticular-onset JIA who were referred between 1988 and 1998 were evaluated. At disease onset, selected clinical and laboratory data were collected as independent variables. A polyarticular disease course, joint erosion, uveitis, and remission were assessed as dependent variables. Longitudinal analyses were performed with the Kaplan-Meier method, and multivariate analysis with the Cox model. RESULTS: After 6 years of followup, the probability of a polyarticular course of disease was 50%, joint erosion was 35%, uveitis was 30%, and remission was 23% in these patients. Joint erosion was strongly associated with a polyarticular course. A high erythrocyte sedimentation rate (ESR) as well as involvement of more than 1 joint or involvement of an upper limb at disease onset were predictors of disease extension. A high ESR was also a strong predictor of a destructive course, and a family history of psoriasis was predictive of uveitis occurrence. No predictive factor for remission could be identified. CONCLUSION: Oligoarticular-onset JIA is a severe disease with frequent complications. Factors predictive of severity in oligoarticular-onset JIA were identified. This could allow early identification of high-risk patient subgroups, warranting a more aggressive therapeutic approach.     

Efficacy, effectiveness and safety of etanercept in monotherapy for refractory psoriatic arthritis: a 26-week observational study

OBJECTIVES: To investigate the efficacy, effectiveness and safety of etanercept, a soluble tumour necrosis factor-alpha receptor, in a prospective observational cohort of patients with refractory psoriatic arthritis and polyarticular involvement. METHODS: Twenty patients with psoriatic arthritis refractory to conventional anti-rheumatic drugs were treated with etanercept 25 mg subcutaneously twice a week for 26 weeks. Efficacy and safety were recorded at weeks 2, 6, 10, 16, 20 and 26. Effectiveness, defined as clinical remission, reduction of 50% in clinical parameters and concomitant NSAID use, was evaluated at 26 weeks. RESULTS: Etanercept therapy was efficacious in this cohort as 85% of the patients met the Psoriatic Arthritis Response Criterion at week 26. Effectiveness of etanercept for the individual patient was demonstrated, since at least 50% of the patients had a 90 and 85% improvement in swollen and tender joint count, respectively, and a 71% improvement in the Health Assessment Questionnaire at week 26. Four patients showed complete remission and NSAIDs were stopped in 10/15 patients. The most common adverse events were upper respiratory tract infections. Interestingly, in two patients psoriasis worsened during the study, unrelated to the course of arthritis. The administration of etanercept was interrupted in three patients for adverse events: one septic bursitis, one myocardial infarction and one tooth abscess. After resolution of the adverse events, etanercept was successfully reintroduced. CONCLUSIONS: Etanercept in monotherapy is efficacious, effective and safe in the majority of patients with refractory psoriatic arthritis.     

Update upon efficacy and safety of etanercept for the treatment of spondyloarthritis and juvenile idiopathic arthritis

TNF-α inhibitors have demonstrated efficacy both as monotherapy and in combination with disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of chronic inflammatory immune-mediated diseases such as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, ankylosing spondylitis (AS), psoriasis (Ps) and/or psoriatic arthritis (PsA) and may be administered off-label to treat disseminated granuloma annulare, systemic lupus erythematosus and systemic sclerosis. There are several TNF-α inhibitors available for clinical use including infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. In this article, we discuss the efficacy and safety of etanercept in the treatment of spondyloarthritis and juvenile idiopathic arthritis (JIA). Etanercept is effective in the treatment of PsA, AS, JIA and uveitis. Independent predictors of achieving a sustained clinical improvement or MDA in children with JIA include shorter disease duration, no concurrent oral corticosteroid use, history of chronic anterior uveitis and age <9 years. IBD incidence was lower in patients receiving etanercept plus MTX. Intra-articular administration of etanercept seems to favor a prompt target joint improvement without serious adverse events. Etanercept improve endothelial function reducing the risk of acute cardiovascular and/or cerebrovascular events. The most commonly reported adverse events were nasopharyngitis, epidermal and dermal conditions, upper respiratory tract infection, cough, headache and fatigue.     

Guidelines on the use of etanercept for juvenile idiopathic arthritis in Japan

Etanercept is a dimeric fusion protein consisting of the extracellular domain of human tumor necrosis factor receptor II (TNFR II, molecular weight 75 kDa) coupled to the Fc region of human immunoglobulin (IgG1). It is produced by recombinant DNA technology by first introducing the gene into Chinese hamster ovarian cells and then purifying the protein from the culture supernatant. The mechanism of action of etanercept consists of binding to serum TNF-α and lymphotoxin (LT)-α (TNF-β), which prevents TNF-α and LT-α from binding to the TNF-α receptor on the plasma membrane of the target cell. Etanercept is currently approved for treating adult rheumatoid arthritis (RA) in more than 70 countries worldwide. In Japan, it was approved for this target group in January 2005. The USA and Europe were the first to approve entanercept for use in treating juvenile idiopathic arthritis (JIA), initially for the treatment of active polyarticular JIA in patients not responding to disease-modifying antirheumatic drugs (USA in May 1999, followed by the EU in February 2000). Thereafter, the drug received approval for the treatment of JIA in many other countries. In Japan, children who have been diagnosed and treated according to Yokota et al. (Mod Rheumatol 17:353–363, 2007), but who have responded poorly to treatment must move onto the next stage of treatment. Such treatments include biological drugs, which, however, should be used with strict adhesion to the indications and exclusion criteria and should be used, for the time being, only by physicians trained on how to use them. In Japan, etanercept was approved in July 2009 for use in children. Although this drug has brought about a revolutionary advance in the treatment of JIA, it is our task to maximize its therapeutic effects and minimize its toxic effects. The guidelines presented here define the indications, exclusion criteria, usage, and evaluation criteria of etanercept for the treatment of polyarticular JIA.     

Course of joint disease in patients with antinuclear antibody-positive juvenile idiopathic arthritis

OBJECTIVE: To describe the patterns and time course of arthritis in patients with antinuclear antibody (ANA)-positive juvenile idiopathic arthritis (JIA). METHODS: We identified patients followed during a 16-year period who had JIA by ILAR criteria, were ANA-positive (i.e., had >or= 2 positive ANA test results at titer >or= 1:160), and had a disease duration >or= 2 years. Demographic and clinical features, including ILAR category and cumulative number and type of joints affected over time, were recorded. RESULTS: A total of 195 patients were studied. The ILAR category was oligoarthritis in 159 patients and rheumatoid factor-negative polyarthritis in 36 patients. The cumulative rate of polyarticular extension in patients with oligoarticular onset was 26%, 38%, 45%, 49%, and 51% at 1, 2, 3, 4, and 5 years, respectively. At disease onset, most patients had monoarthritis and 95% had 相似文献