Comprehensive assessment of medication risk-benefit in autoimmune disease for healthy pregnancies (care-HP)

The National Institute of Child Health and Human Development awarded Harvard Pilgrim Health Care, Inc. $703,092 on September 2, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to conduct a comprehensive assessment of advanced therapeutic medications in autoimmune disease during pregnancy.

The project, titled "Comprehensive Assessment of Medication Risk-Benefit in Autoimmune Disease for Healthy Pregnancies" (CARE-HP), will evaluate safety and efficacy outcomes for biologics and Janus kinase inhibitors used to treat autoimmune diseases in pregnant women and their infants. The work builds on methodology developed in an ongoing parallel project (BOOST-HP) and leverages existing research infrastructure including billing records from private and public insurance covering more than 13 million pregnancies and over 92,000 pregnancies among women with autoimmune diseases. The project will use a two-step approach combining data-mining to examine thousands of outcomes simultaneously, followed by confirmatory studies, to generate condition-specific and drug-class-specific assessments across a broad range of maternal and infant outcomes.

Harvard Pilgrim Health Care's Office of Sponsored Programs in Canton, Massachusetts, serves as the recipient. The period of performance runs through June 30, 2031.

Abstract

Advanced treatments (advtx) such as biologics and janus kinase inhibitors for patients with autoimmune disease (aid) have grown rapidly, but there is limited evidence on their outcomes in pregnancy. Decisions to continue, stop or start advtx during pregnancy rely on a small number of observational studies, mostly conducted among patients with inflammatory bowel disease, that do not capture the full breadth of outcomes and clinical scenarios to define advtx benefit-risk. Given the complex interplay of autoimmunity and reproduction, with some aids worsening and others improving during pregnancy, there is a need for condition- specific evaluations that compare the full breadth of outcomes affecting mother and child. Such breadth requires massive data repositories and scalable approaches paired with sophisticated designs to capture heterogeneous treatment effects and accelerate the availability of clinically relevant evidence. Building on our prior work, we propose a comprehensive investigation of advtx considering pregnancy, maternal and infant outcomes. We will use the methodology developed for drug evaluations in pregnancy in our ongoing project big data approaches for safe therapeutics in healthy pregnancies (boost-HP), which optimizes safety assessments in two steps: data-mining, which facilitates simultaneous examination of thousands of outcomes, followed by confirmatory studies; and leverage our research infrastructure, including billing records from private and public insurance for >13M pregnancies and >92,000 among women with aids. Comprehensive assessment of medication risk-benefit in autoimmune disease for healthy pregnancies (care-HP) aims to cut through silos of specialty care by including key aids that rely on similar therapies, allowing for disease-specific and drug class-specific assessments across a broad range of outcomes. We consider two clinically relevant scenarios: (a) head-to-head comparisons within advtx classes or single agents or VS. Conventional disease modifying therapy, and (b) advtx continuation VS. Discontinuation. Using sophisticated methods for confounding control and assessment of treatment effect heterogeneity across aids, the specific aims are to: (1) evaluate the risk of pregnancy loss following advtx use; (2) scan for advtx associations with a broad range of maternal pregnancy complications, using data-mining methodology, followed by formal pharmacoepidemiologic studies of the top two prioritized signals from data-mining, and five pre-specified outcomes (preterm births, aid flares, hospitalization, serious infection, and preeclampsia); (3) scan for advtx associations with congenital malformations among aid-specific mother-infant linked cohorts, followed by formal pharmacoepidemiologic studies of the top two prioritized signals gleaned from data-mining, and four pre-specified outcomes (small for gestational age, serious infections, autism spectrum disorder and attention deficit/hyperactivity disorder). Our long-term goal is to develop comprehensive evidence on advtx benefit-risk that can support personalized treatment plans for pregnant patients with various aids.