Novel Method to Collect Medication Adverse Events in Juvenile Arthritis: Results From the Childhood Arthritis and Rheumatology Research Alliance Enhanced Drug Safety Surveillance Project

Abstract

Objective. Few 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. Methods. Participating 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. Results. Thirty-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. Conclusion. The 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.

Adverse drug reactions associated with the use of biological agents

“…ADRs associated with biotech drugs occur more frequently in women, as documented in other studies conducted in Spain (82.9%) [13], the United States (75.5%) [14] and Italy (54.3-71.3%) [4,15], in agreement with the present finding. This is probably because many of the pathologies for which biotech drugs are used have a known predominance in women, including autoimmune diseases such as rheumatoid arthritis [16,17] or oncological diseases [18], which expose women to a greater probability of use and of developing ADRs.…”

“…In addition, according to severity, 22.6% of the reports were classified as serious, consistent with what was found in Italy (9.8-25.5%) [15,23], Japan (18.5-23.4%) [20,26], Spain (21.7%) [19], Brazil (25.0%) [22] and Korea (32.3%) [12]. Among severe reactions, the possibility of developing cancer, infections, hypersensitivity reactions and major cardiovascular events is described in the literature [10,12,14,19,22], and fatalities can also occur, which in this report corresponded to 0.1% of all ADRs, a rate lower than that documented in another study [27]. Death does not correspond to an adverse event but rather to a fatal outcome that can also be explained by the underlying disease of the patient.…”

“…The ADRs most documented in different studies are those related to infections [14,15,[19][20][21], general manifestations or those associated with the administration of biotech drugs [12,22,23] and those related to the skin or subcutaneous tissues [4,12,23,24]. However, the present study found that the most common ADRs were those related to the respiratory tract, diverging with what was found in other studies where their frequency was much lower (16.8 vs. 3.8-10.8%) [4,12,24], probably because we included in this category infections such as pneumonia and bronchitis, among others, which increased the proportion of respiratory tract-related ADRs.…”

Infection-Related Death among Persons with Refractory Juvenile Idiopathic Arthritis

“…See section in text on MAS versus Multiorgan Failure. Alb, serum albumin level (reference 38 –53 g/L); ALT, serum alanine transaminase level (reference 0–40 U/L); CRP, C-reactive protein (reference 0–5 mg/dL); ESR, erythrocyte sedimentation rate (Westergren; reference 1 – 10 mm/h); Ferr, serum ferritin level (reference 20 –60 μg/L); Fib, serum fibrinogen level (reference 1.5–4.0 g/L); Na, serum sodium level (reference 135–145 mmol/L); Ne, absolute neutrophil count; PLT, absolute platelet count; TG, serum triglyceride level (reference 0.5–1.8).…”

“…Monitoring the safety and reporting the side effects, including severe infections and deaths, of new biological DMARDs is a priority of national and international patient registries and multicenter, international collaborative research consortiums, such as the Childhood Arthritis and Rheumatology Research Alliance, Pediatric Rheumatology International Trials Organisation, Pediatric Rheumatology Collaborative Study Group, and Single Hub and Access Point of Care for Pediatric Rheumatic Diseases in Europe ( 37 , 38 ). However, reporting of deaths is still inconsistent.…”