Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs: combined data of more than 15,000 patients from Pharmachild and national registries

Abstract

BackgroundThe availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden.MethodsDescriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available.ResultsData from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1–6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor–negative polyarthritis (range of 24.6–29.9%). Methotrexate (61–84%) and etanercept (24%–61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7–42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4–30.1%) followed by gastrointestinal disorders (11.5–19.6%). The most frequent ESIs were infections (75.3–89%).ConclusionsThis article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA.Registry registrationThe Pharmachild registry is registered at ClinicalTrials.gov (NCT01399281) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) (http://www.encepp.eu/encepp/viewResource.htm?id=19362). The BiKeR registry is registered at ENCePP (http://www.encepp.eu/encepp/viewResource.htm?id=20591).Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1780-z) contains supplementary material, which is available to authorized users.

Biologic Therapies in Polyarticular Juvenile Idiopathic Arthritis. Comparison of Long‐Term Safety Data from the German BIKER Registry

“…The background risk for malignancies in JIA patients might be higher than that of the general population. The Pharmachild registry reported a similar rate of malignancies, although with fewer hematopoietic malignancies (13). In a more recent study, they compared patients with JIA who were using TNFi with those who were not using TNFi and found that treatment with TNFi did not appear significantly associated with the development of malignancy (20).…”

“…In the Pharmachild registry, demyelination was also a rare event (13). In the Pharmachild registry, demyelination was also a rare event (13).…”

Identifying rheumatic disease patients at high risk and requiring shielding during the COVID-19 pandemic

“…13 Combined data from juvenile biologic registers suggests that infections are common with single or combined treatment but corticosteroids are the most important factor influencing infection risk. [14][15][16][17][18] Recurrent infection rates are also increased in patients on biologics, with a 14% annual risk of recurrent infection following an index event. 17 Respiratory infections were the most frequent (44% of all events) and increasing age and polypharmacy were significant predictors of infection recurrence.…”

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

“…Treatments in JIA with synthetic and biologic DMARDs are expected to increase the frequency of common infections and the risk of serious and opportunistic infections (OI) [23,[30][31][32][33][34], including especially tuberculosis in some geographic areas [35][36][37]. In order to tackle the long-term safety and efficacy evaluations, the Paediatric Rheumatology INternational Trials Organization (PRINTO) started in 2011 the "Pharmacovigilance in Juvenile Idiopathic Arthritis patients" (Pharmachild), an observational international registry supported by a European Union grant [38,39].…”