(011) Enhanced Pharmacovigilance to Contextualize 13 years of Monitoring: The Gilenya Pregnancy Registry put in Perspective with the Fingolimod PRegnancy outcomes Intensive Monitoring (PRIM) Program

Background: The Gilenya Pregnancy Registry (GPR) (established in 2011) is a Post-Marketing Requirement. The fingolimod PRegnancy outcomes Intensive Monitoring (PRIM) program was implemented using pharmacovigilance (PV) data to complement GPR and overcome recruitment challenges. Both studies assess maternal, fetal, and infant outcomes after exposure to fingolimod immediately before or during pregnancy.
With study methods in mind, this work aims to reconcile and elucidate the differing findings between studies.

Objectives: To contextualize GPR major congenital malformations (MCM) using fingolimod PRIM data.

Methods: GPR is a global pregnancy registry with primary data collection. US patients can enroll directly; elsewhere enrollment is via recruitment sites. PRIM is an enhanced PV system based on spontaneously reported pregnancies. Patients and health care professionals (HCPs) initiate reporting.
Current analyses focus on prospective cases. Primary outcome is MCM per the European Surveillance of Congenital Anomalies and Twins (EUROCAT) guidelines, assessed independently. Data were stratified by region (Germany, US/Canada and “Other”) and reporter (patient or HCP); common variables are summarized with descriptive statistics (%). PRIM prevalence, expressed per 100 live births (LBs), was standardized to the GPR population by region and reporter.

Results: As of 28-Feb-2023, GPR has enrolled 206 prospective cases, including 167 LBs; PRIM 758 cases, including 549 LBs. Regional differences exist, with GPR cases mainly from Germany (N=111; 53.9%) or “Other” (N=62; 30.1%), while PRIM cases from “Other” (N=905; 61.1%) or US/Canada (N=464; 31.3%).
Per design, 100% of US/Canada GPR cases were non-HCP reported. These represented 37.7% in PRIM.
Overall, the GPR US/Canada population reported more pregnancy risk factors compared to Germany or “Other”, including obesity (36.7% vs. 18.0% vs. 18.0%) and pre-existing medical conditions (45.5% vs. 25.2% vs. 11.3%).
Overall MCM prevalence in GPR (6.6%) is higher than in PRIM (2.7%), mainly driven by US/Canada (GPR (12.5%) vs. PRIM (2.6%)). When standardized to the GPR population, PRIM MCM prevalence is 5.8%, like that in GPR.

Conclusions: This work underscores the importance of considering underlying population characteristics at study and patient level for robust evaluations and result contextualization. Different MCM prevalence estimates in a registry and PV data were reconciled for the first time, considering study population. However, potential ascertainment bias, confounding and maternal risk factors compromise causality assessment; therefore, the GPR population may not represent the general MS population.