Sulfasalazine in the treatment of juvenile chronic arthritis: A randomized, double-blind, placebo-controlled, multicenter study

Objective. To assess the efficacy, tolerability, and safety of sulfasalazine (SSZ) in the treatment of juvenile chronic arthritis (JCA). Methods. We conducted a 24-week randomized, placebo-controlled, double- blind, multicenter study of patients with active JCA of both oligoarticular and polyarticular onset. Patients were treated with a dosage of 50 mg/kg/day of SSZ (maximum 2,000 mg/day) or placebo. The efficacy variables were joint scores, physician's, parents', and patient's overall assessments, and laboratory parameters of inflammation. Results. Of the 69 patients enrolled, 52 (75%) completed the trial. Six patients (18%) withdrew from the placebo group, and 11 (31%) withdrew from the SSZ group (P = 0.18). In the intention- to-treat analysis of end point efficacy, between-group differences were significant for the overall articular severity score (P = 0.02), all global assessments (P = 0.01), and the laboratory parameters (P < 0.001). Adverse events occurred more frequently in the SSZ group and were the main reason for withdrawal (P < 0.001), but in all instances, these events were transient or reversible upon cessation of treatment. Conclusion. The results of this first placebo-controlled study show that SSZ is effective and safe in the treatment of children with oligoarticular- and polyarticular-onset JCA, although it was not well tolerated in one-third of the patients

Long‐term outcome of juvenile idiopathic arthritis following a placebo‐controlled trial: sustained benefits of early sulfasalazine treatment

Objectives: A previous 24- week randomised trial demonstrated that sulfasalazine ( SSZ) treatment was superior to placebo ( PLAC) in suppressing disease activity in patients with oligo- and polyarticular onset juvenile idiopathic arthritis ( JIA). The current study determines the long- term outcome of the trial participants and evaluates whether the benefits of SSZ allocation are sustained over time. Methods: Between 2001 and 2003, 32 SSZ and 29 PLAC patients ( 90% of all patients) were prospectively examined clinically and by chart review, median 9 years ( range 7 to 10) after trial inclusion. In the follow- up assessment, variables of the American College of Rheumatology Pediatric 30 ( ACR Pedi 30) criteria were collected. The assessor was blinded to trial treatment allocation. Results: After the trial, patients had been routinely followed in rheumatology referral centres, and treated at the discretion of the attending physician. Almost all patients continued or started disease- modifying antirheumatic drugs ( DMARDs) ( SSZ 91%, PLAC 93%; SSZ treatment in about 80%). DMARD treatment appeared less intensive in the SSZ group as evidenced by a significantly shorter duration of SSZ use ( median 2.5 vs 5.2 years; p = 0.02) and a trend towards less use of methotrexate and other DMARDs. More than onethird of the patients reported long periods of non- compliance with DMARD treatment in both groups. At follow- up, 74% of the patients had active joints, and 30% showed active polyarthritis. Almost all outcome scores were better for SSZ compared with PLAC patients. Differences ( often exceeding 50%) were significant for the number of active joints, patients' overall well- being, number of patients with episodes of clinical remission off medication ( CROM) and duration of these episodes, patients in CROM and ACR Pedi 30 response at follow- up. Additional exploratory analyses performed to detect potential confounders related to patient characteristics or follow- up treatment showed that DMARD treatment compliance was positively correlated with an ACR Pedi 30 response ( odds ratio 3.8, 95% confidence interval ( CI) 1.1 to 13.4; p = 0.03). Adjusted for compliance, an SSZ patient was 4.2 times as likely as a PLAC patient to be an ACR Pedi 30 responder at follow- up ( 95% CI 1.3 to 14.3; p = 0.02). Conclusions: This follow- up study shows that effective suppression of disease activity by SSZ treatment early in active disease in JIA patients has beneficial effects that persist for many years. Given these results, compliance with DMARD treatment deserves serious attention

Plant dispersal in a lowland stream in relation to occurrence and three specific life-history traits of the species in the species pool

1 The diversity and abundance of viable diaspores trapped at the downstream end of a 15-km lowland stream were quantified and related to five potentially predicting variables: species' occurrence in the species pool, distance to the nearest stand and the life-history traits seed buoyancy, seed production and plant height. 2 From 126 samples, 106 614 individuals of vascular plants developed, 95.8% from vegetative diaspores and 4.2% from seeds. Among these plants, three free-floating, 12 submerged, 22 emergent ( aquatic) and 70 riparian (semi-aquatic and terrestrial) species were recorded, respectively, accounting for 24.3%, 71.9%, 1.2% and 2.6% of the total number of viable diaspores trapped. 3 Of the free-floating, submerged and emergent species, 100%, 98.9% and 23.7% of the diaspores were vegetative, respectively, whereas it was 2.9% for riparian species. 4 Diaspores of 79% of the total number of aquatic species and 40% of riparian species observed in the established vegetation were trapped. Minimal dispersal distances ranged from 0 to 6 km. 5 Multiple regression analysis conducted for submerged species, showed that 71% of the variation in the diaspore pool could be predicted by occurrence of species in the vegetation. For emergent species, seed production and occurrence of species explained 54% of the variation, seed production being most important. Mean seed buoyancy of emergent species was higher than that of the other groups. For riparian species, seed production, occurrence and buoyancy explained 48% of the variation in the diaspore pool. Seed production per plant was the most important variable. Linear regression revealed a negative relationship between distance and abundance of the diaspore pool for submerged and riparian species. 6 We conclude that the occurrence of species in the species pool is a significant predictor for the dispersal of free-floating and submerged aquatics that rely on vegetative propagation. Seed production and buoyancy are of additional importance with regard to emergent aquatics. Riparian species with a limited terrestrial dispersal capacity may largely extend their range by hydrochory. That is, if they produce large amounts of ( small) seeds and provided that these can reach the water body. Buoyancy and high frequency and abundance in the established vegetation promote this dispersal capacity as well