Associate Director, Benefit-Risk Epidemiology Janssen Pharmaceuticals, United States
Background: Recent reports related to in utero exposure to biologics led to recommendations to delay live vaccinations for infants due to concerns of reduced effectiveness and/or vaccine-related disease. These delays increase the risk of children contracting vaccine preventable diseases, yet cessation of biologics during pregnancy may result in increased autoimmune disease activity for the mother, raising complex benefit-risk questions.
Objectives: To develop a conceptual framework for benefit-risk assessment based on the key benefits and risks mothers would consider for themselves and their children when continuing a biologic during pregnancy.
Methods: We adopted a structured benefit-risk framework to define the decision context and key domains and attributes for benefits and risks of biologic use in pregnancy. Domains and attributes were selected through a literature search of indications for biologics and then refined in alignment with key stakeholders in epidemiology, gynecology, immunology, and neonatology.
Results: The two participants in the framework are the mother taking the biologic and the infant exposed to the biologic in utero. The indications are all diseases warranting biologics and the treatment alternatives are continuing versus stopping a biologic during pregnancy. The mother’s benefit domains are symptom improvement, including the attributes of decreased hospitalization, outpatient visit, and other concomitant medication use (e.g. steroids), and improved pregnancy outcomes including the attributes of reduced chance of preeclampsia and miscarriage. The benefit domain for the infant is improved health status, including the attributes of reduced chance of preterm birth and NICU hospitalization, and improved quality of life. The mother’s risk domains are risks associated with biologics in the general population: increased risk of serious infection, malignancy, and drug/allergic reaction. Risk domains for the infant include increased risk of malignancy, drug/allergic reaction, congenital malformations, and potential decline in immunity. Decline in immunity attributes are increased risk of infection and delays in immunization.
Conclusions: The intent of this conceptual framework is to motivate establishing a consortium to identify data sources and analyses that can quantify the framework. The goals are to inform future evidence-based analyses to support physician and patient decisions for biologic use and inform guidelines regarding biologic treatment for those who are or may become pregnant.
