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.

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

“…Despite the widespread use of these drugs, there is still a lack of knowledge regarding the assessment of the long-term safety of the biologics in JIA. In this context, the role of national and international registries becomes an important source of data [39,[45][46][47].…”

Pediatric registries at the Food and Drug Administration: design aspects that increase their likelihood of success

“…One approach used by 60% (6/10) of successful registries was to start the registry as a disease‐based registry. Disease‐based registries have several advantages over drug‐based registries, including larger sample size, the ability to compare treatment approaches, the ability to follow patients over time irrespective of current therapy, and long‐term follow‐up . For these reasons, disease‐based registries can be particularly valuable when evaluating rare diseases or small patient populations, as often occurs in pediatrics .…”

Orphan Therapies: Making Best Use of Postmarket Data

“…To truly eliminate data fragmentation among these specialized populations, a disease-based registry is required. 4,5 However, diseasebased registries require substantial financial resources over long periods of time, and it is unclear whether a sustainable funding model exists. We believe the model we propose here is a plausible alternative, because it takes advantage of existing requirements for postmarket registries and uses these data for analysis without requiring manufacturers to share them with one another.…”

“…They can become information silos, delaying the ability to answer important public health questions on the natural history of the disease, class-wide effects, or comparative benefits and risks. 4,5 One remedy is to create a distributed electronic health data network, [6][7][8] which can increase sample size without centralizing or combining patient-level data.…”