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.     

Heterogeneity of hla associations in systemic onset juvenile rheumatoid arthritis

Two genetic markers, HLA-Bw35 and HLA-B8, are found to be associated with “febrile” or “systemic” onset juvenile rheumatoid arthritis (JRA). Evidence is presented that JRA patients are probably heterogeneous with respect to these antigens.     

Seasonal variation in systemic onset juvenile rheumatoid arthritis in Israel.

OBJECTIVE: To determine whether there is a seasonal peak onset of systemic juvenile rheumatoid arthritis (SOJRA) suggestive of an infectious etiology. We examined the seasonal variability of SOJRA in Israel. METHODS: A multicenter retrospective chart review of 59 patients with SOJRA, enrolled from 10 rheumatology units or pediatric departments in Israel. All patients met defined criteria of SOJRA. RESULTS: Fifty-nine patients (31 female, 28 male) were followed from 1982 to 1997. Their mean age was 7.1 +/- 4.3 years (range 0.9-16). Forty-six were Jewish and 13 were Arabs or of Bedouin origin. Eighteen patients (31%) had disease onset in the winter, 16 (27%) in the spring, 12 (20%) in the summer, and 13 (22%) in the fall. Twenty-eight patients had a monophasic disease subtype, while 31 had a chronic or cyclic subtype. The seasonal onset in the patients with the monophasic type versus the chronic or the cyclic type shows 7 versus 11 in the winter, 7 versus 9 in spring, 8 versus 4 in summer, and 6 versus 7 in fall, respectively. CONCLUSION: There is no seasonal pattern to SOJRA disease onset in Israel. However, the disease onset of patients having the chronic or the polycyclic subtype tends to be more common in winter and spring. Since patients with this type have more severe disease, it is possible that another specific infectious agent is one of the factors involved in the pathogenesis of the disease. Larger sampling and multicenter studies are required to clarify this point.     

High dose, alternate day corticosteroids for systemic onset juvenile rheumatoid arthritis

OBJECTIVE: To determine the safety and efficacy of high dose alternate day (qod) prednisone as therapy in acute systemic onset JRA (SOJRA). METHODS: A retrospective chart review was performed of all active patients with SOJRA at our institutions who began high dose qod prednisone (n = 20; 9 male, 11 female; mean age of onset 6.5 yrs, range 1.2-18.6). Patients were followed for at least one year after initiation of high dose qod prednisone. Disease activity (fever, rash, active joint count, complete blood cell count, erythrocyte sedimentation rate, ESR) and possible side effects of treatment were assessed at each visit. RESULTS: Within a mean of 2.1 months (range 1-5), systemic features (fever, rash, serositis, coagulopathy) in all patients had resolved and there was significant improvement in laboratory indices of disease activity. Doses ranged from 1 to 5.8 mg/kg qod (actual doses: 50-400 mg qod), with a mean of 3.2 mg/kg. No patient had to restart daily prednisone. The only major side effect was the development of mild cataracts in one patient. Height standard deviation scores (SDS) remained within normal range in all but 2 patients. Clinical improvement was maintained in all patients, as measured by lack of systemic symptoms, and decreased active joint count. Repeated measures of analysis of variance revealed significant improvement in all laboratory tests (white blood cell count, hemoglobin, platelet count, ESR) measured at 0, 6, and 12 months (p < 0.001). Nine of the 20 patients continued qod prednisone more than 12 months beyond the study period (mean 5.2 yrs, range 3-8). The only additional side effects were a vertebral crush fracture in one patient and possible avascular necrosis in another. Height SDS did not change significantly over the 3 year period after the initiation of qod prednisone (p > 0.05). CONCLUSION: High dose qod prednisone appears to be effective in controlling the systemic features of SOJRA and was well tolerated. Side effects attributable to corticosteroids, including growth suppression, were minimal.     

Prognosis in juvenile rheumatoid arthritis with systemic onset. A follow-up study

Thirty-three patients with systemic onset JRA were followed up for 4 to 24 years (median 10 years). None had positive RF or ANA. Most patients developed polyarthritis. Cardiac involvement occurred in 14 patients (42%). Cardiac prognosis was good for pericarditis but seemed to be worse for myocarditis or perimyocarditis. Three patients contracted renal amyloidosis (9%). Severe growth retardation was observed in 39 per cent. Half of the patients had low activity or were in remission after in average 5.9 years' duration of the disease. Seventy per cent of the patients were in a good functional state. Patients with less than average radiological progression during the first 5 years of disease and those with onset of disease after the age of 5, seemed to have a better functional prognosis.     

HLA gene frequencies in children and adults with systemic onset juvenile rheumatoid arthritis

The HLA genetic region was studied in 51 patients with systemic onset juvenile rheumatoid arthritis: 35 with childhood onset and 16 with adult onset (adult Still's disease). HLA genotypes were established by including family members, 261 of whom were also typed in the study. The most marked difference between patients and controls involved the HLA-DR4 gene, which occurred with a frequency of 0.348 in the childhood onset patients and 0.170 in the controls (chi 2 = 8.97, P = 0.0028, adjusted P = 0.017). In contrast, the adult onset patients showed a marginal increase in HLA-DR7, but were similar to controls with respect to HLA-DR4. HLA-Bw35 was increased in children with systemic onset disease, in accordance with earlier findings. The results suggest that patients with systemic onset juvenile rheumatoid arthritis have complex HLA associations which are different in childhood onset and adult onset disease.     

Anakinra treatment for systemic onset juvenile idiopathic arthritis (SOJIA)

SIR, Systemic onset juvenile idiopathic arthritis (SOJIA) accountsfor 10–20% of all patients with JIA, but it accounts forincreased morbidity and mortality compared with other formsof JIA [1]. A significant number of patients have ongoing diseaseactivity despite aggressive treatment. A follow-up study foundthat the probability of disease remission 10 yrs after onsetwas only 37% [2]. Despite a variety of treatments some childrenwith SOJIA have a refractory course with significant morbidity.Pasqual et     

Immune abnormalities in the pathogenesis of juvenile rheumatoid arthritis

This article reviews the immune abnormalities involved in the pathogenesis of juvenile rheumatoid arthritis (JRA). We review both the humoral and cellular immune systems of children with JRA with emphasis on the possible role of these immune abnormalities in the pathogenesis of JRA.     

Update on the medical treatment of juvenile idiopathic arthritis

Many exciting developments in the treatment of juvenile idiopathic arthritis (JIA) have emerged recently, including new tools to assess the results of clinical trials (eg, the definition of remission and a radiologic scoring tool). New controlled studies examined the equivalence of meloxicam to naproxen, the efficacy of leflunomide but the superiority of methotrexate, and the use of infliximab in polyarthritis JIA. Initial studies have shown the potential of anti-interleukin (IL)-1 and anti-IL-6 receptor antibody therapy for systemic JIA. Corticosteroid-sparing medications including the use of "biologic modifiers" for JIA-associated uveitis have been described. Evidence-based guidelines for the main subtypes of JIA have been published. However, good evidence on the treatment of several disease subtypes is still lacking. Studies of new medications and the use of combination therapy, including aggressive induction therapy early in the disease course, are necessary to continue improving the outcome of JIA patients.     

Tarsal ankylosis in juvenile and adult onset rheumatoid arthritis

It has been suggested that tarsal arthritis with ankylosis may be characteristic of late onset Still's disease. In our study 16 of 88 (18%) patients with juvenile rheumatoid arthritis (JRA) and 22 of 97 (23%) patients with adult RA had radiographic findings of tarsal joint ankylosis. In our patients, tarsal bony fusion was not related to type of disease onset, age of onset or sex; rather it was related to a longer duration of disease. Tarsal ankylosis should not be regarded as a special feature of Still's disease since it can also be seen in adult RA.