Stoll, Matthew Laurence

Objective Systemic juvenile idiopathic arthritis–associated lung disease (SJIA‐LD) is a life‐threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA‐LD detection, characterize overall disease courses, and measure long‐term outcomes. Methods This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. Results We enrolled 41 patients with SJIA‐LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow‐up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty‐four percent of patients carried the HLA‐DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA‐LD also showed markedly elevated serum interleukin‐18 (IL‐18), variable C‐X‐C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti–IL‐1/6 biologics and addition of other immunomodulatory treatments and lung‐directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. Conclusion Patients with SJIA‐LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.

ObjectiveFew data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product‐based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4‐year (2008–2012) EDSSP.MethodsParticipating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6‐month period. Reporting rates were calculated per 100 person‐years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution.ResultsThirty‐seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person‐years (95% CI 0.95–1.19). The rates for SAEs and IMEs were 0.54 per 100 person‐years (95% CI 0.45–0.63) and 0.53 per 100 person‐years (95% CI 0.49–0.62), respectively.ConclusionThe EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product‐based registry.