Using registries to identify adverse events in rheumatic diseases

Abstract

The proven effectiveness of biologics and other immunomodulatory products in inflammatory rheumatic diseases has resulted in their widespread use as well as reports of potential short- and long-term complications such as infection and malignancy. These complications are especially worrisome in children who often have serial exposures to multiple immunomodulatory products. Post-marketing surveillance of immunomodulatory products in juvenile idiopathic arthritis (JIA) and pediatric systemic lupus erythematosus is currently based on product-specific registries and passive surveillance, which may not accurately reflect the safety risks for children owing to low numbers, poor long-term retention, and inadequate comparators. In collaboration with the US Food and Drug Administration (FDA), patient and family advocacy groups, biopharmaceutical industry representatives and other stakeholders, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the Duke Clinical Research Institute (DCRI) have developed a novel pharmacosurveillance model (CARRA Consolidated Safety Registry [CoRe]) based on a multicenter longitudinal pediatric rheumatic diseases registry with over 8000 participants. The existing CARRA infrastructure provides access to much larger numbers of subjects than is feasible in single-product registries. Enrollment regardless of medication exposure allows more accurate detection and evaluation of safety signals. Flexibility built into the model allows the addition of specific data elements and safety outcomes, and designation of appropriate disease comparator groups relevant to each product, fulfilling post-marketing requirements and commitments. The proposed model can be applied to other pediatric and adult diseases, potentially transforming the paradigm of pharmacosurveillance in response to the growing public mandate for rigorous post-marketing safety monitoring.

Keywords: biologic products; immunomodulatory therapy; juvenile rheumatic disease; medication safety.

FIGURE 1

Pediatric pharmaceutical regulation timeline. The major federal legislative actions targeting improving appropriate labeling of clinical safety and efficacy data for children are shown.

FIGURE 2

CARRA Registry and CARRA-CoRe data architecture. The current CARRA Registry infrastructure is shown on the left panel of the figure. The right panel illustrates components that extend the existing CARRA Registry infrastructure for CARRA-CoRe functions.

FIGURE 3

CARRA-CoRe organizational structure. The CARRA-CoRe structure is designed to insure scientific independence through the Scientific Oversight Committee, while the Steering Committee is responsible for strategy, operational oversight, resources, involvement of industry sponsors, and input from Advisory Committees.