Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis.

OBJECTIVE: To assess health-related quality of life (HRQOL) in abatacept-treated children/adolescents with juvenile idiopathic arthritis (JIA). METHODS: In this phase III, double-blind, placebo-controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to ≥1 disease-modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4-month open-label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined "responders") were randomized to abatacept or placebo (plus MTX) in the 6-month double-blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100-mm visual analog scale), the Children's Sleep Habits Questionnaire, and a daily activity participation questionnaire. RESULTS: A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept-treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents' usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus -1.3 [P = 0.109] school days/month and parents' usual activity days/month, respectively, in abatacept- versus placebo-treated subjects). CONCLUSION: Improvements in HRQOL were observed with abatacept, providing real-life tangible benefits to children with JIA and their parents/caregivers.

Systematic review of hydroxychloroquine use in pregnant patients with autoimmune diseases.

OBJECTIVE: The purpose of this study is to compare the incidence of congenital defects, spontaneous abortions, number of live births, fetal death and pre-maturity in women with autoimmune diseases taking HCQ during pregnancy. METHODS: The authors searched MEDLINE, Cochrane data base, Ovid-Currents Clinical Medicine, Ovid-Embase:Drugs and Pharmacology, EBSCO, Web of Science, and SCOPUS using the search terms HCQ and/or pregnancy. We attempted to identify all clinical trials from 1980 to 2007 regardless of language or publication status. We also searched Cochrane Central Library and http://www.Clinical trials.gov for clinical trials of HCQ and pregnancy. Data were extracted onto standardized forms and were confirmed. RESULTS: The odds ratio (OR) of congenital defects in live births of women taking HCQ during pregnancy was 0.66, 95% confidence intervals (CI) 0.25, 1.75. The OR of a live birth for women taking HCQ during pregnancy was 1.05 (95% CI 0.58, 1.93). The OR of spontaneous abortion in women taking HCQ during pregnancy was 0.92 (95% CI 0.49, 1.72). The OR of fetal deaths in women taking HCQ during pregnancy was 0.97 (95% CI 0.14, 6.54). The OR of pre-mature birth defined as birth before 37 weeks in women taking HCQ during pregnancy was 1.10 (95% CI 0.75, 1.61). CONCLUSION: HCQ is not associated with any increased risk of congenital defects, spontaneous abortions, fetal death, pre-maturity and decreased numbers of live births in patients with auto-immune diseases.

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial.

BACKGROUND: Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. METHODS: We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. FINDINGS: Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who continued abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups. Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, both in controls (p=0.50). INTERPRETATION: Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. FUNDING: Bristol-Myers Squibb.

MRI findings of rhabdomyolysis from streptococcal pharyngitis.

Rhabdomyolysis has been described as a rare sequela of severe infections by group A streptococcus related to toxic shock syndrome in adults. Streptococcal pharyngitis, on the other hand, has never been reported to cause rhabdomyolysis. We report a case of rhabdomyolysis in a child after an uncomplicated course of group A streptococcal pharyngitis. Although MRI of rhabdomyolysis from other causes has been described in a few case reports, this is a unique MRI description of its occurrence with streptococcal pharyngitis.

Duration of illness is an important variable for untreated children with juvenile dermatomyositis.

OBJECTIVE: To evaluate the impact of duration of untreated symptoms in children with juvenile dermatomyositis (JDM) on clinical and laboratory status at diagnosis. STUDY DESIGN: We examined physical and laboratory data from the first physician visit for 166 untreated children with JDM. Disease activity scores (DASs) assessed skin and muscle involvement. Height and weight were compared with the National Health and Nutrition Examination Survey III dataset. Duration of untreated illness was designated as the time from first sign of rash or weakness to diagnostic visit. RESULTS: Boys and girls with untreated JDM were shorter and lighter than national norms (P > .0005 for both), and nonwhite children were weaker than white children (P > .0005). Older children had more dysphagia (P = .017) and arthritis (P > .001). Duration of untreated JDM was negatively associated with DAS weakness (P > .0005), unrelated to DAS skin, and positively associated with pathological calcifications (P = .006). With untreated disease > or = 4.7 months, serum levels of 4 muscle enzymes (aldolase, lactic dehydrogenase, creatine kinase, serum glutamic-oxaloacetic transaminase/aspartate aminotransferase) tended toward normal (P > .01 for each). CONCLUSIONS: Duration of untreated symptoms is an important variable and should be included in decisions concerning both diagnostic criteria and intensity of therapy for children with JDM.

History of infection before the onset of juvenile dermatomyositis: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry.

OBJECTIVE: To obtain data concerning a history of infection occurring in the 3 months before recognition of the typical weakness and rash associated with juvenile dermatomyositis (JDM). METHODS: Parents or caretakers of children within 6 months of JDM diagnosis were interviewed by the registry study nurse concerning their child's symptoms, environment, family background, and illness history. Physician medical records were reviewed, confirming the JDM diagnosis. RESULTS: Children for which both a parent interview and physician medical records at diagnosis were available (n = 286) were included. Diagnoses were as follows: definite/probable JDM (n = 234, 82%), possible JDM (n = 43, 15%), or rash only (n = 9, 3%). The group was predominantly white (71%) and had a girl:boy ratio of 2:1. Although the mean age at onset was 6.7 years for girls and 7.3 years for boys, 25% of the children were < or =4 years old at disease onset. In the 3 months before onset, 57% of the children had respiratory complaints, 30% had gastrointestinal symptoms, and 63% of children with these symptoms of infection were given antibiotics. CONCLUSION: This study provides evidence that JDM affects young children. The symptoms of the typical rash and weakness often follow a history of respiratory or gastrointestinal complaints. These data suggest that the response to an infectious process may be implicated in JDM disease pathogenesis.