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

Arthritis Res Ther. 2018 Dec 27;20(1):285. doi: 10.1186/s13075-018-1780-z.

Abstract

Background: The 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.

Methods: Descriptive 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.

Results: Data 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%).

Conclusions: This 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 registration: The 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 ).

Keywords: Adverse events; Biologics; Juvenile idiopathic arthritis; Methotrexate; Registry; Safety.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Juvenile / diagnosis
  • Arthritis, Juvenile / drug therapy*
  • Biological Products / adverse effects
  • Biological Products / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Monitoring
  • Etanercept / adverse effects
  • Etanercept / therapeutic use
  • Female
  • Humans
  • Male
  • Methotrexate / adverse effects
  • Methotrexate / therapeutic use
  • Pharmacovigilance*
  • Prospective Studies
  • Registries / statistics & numerical data*
  • Retrospective Studies
  • Synthetic Drugs / adverse effects
  • Synthetic Drugs / therapeutic use*
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Biological Products
  • Synthetic Drugs
  • Etanercept
  • Methotrexate

Associated data

  • ClinicalTrials.gov/NCT01399281