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Evaluation Video

Oral Presentation

Session: EmBRACEing Collaborations for Benefit-Risk Decision Making

Impact of Risk Evaluation and Mitigation Strategies on Teratogenic Medications Among Publicly and Privately Insured Reproductive-Age Women

Monday, August 26, 2024
2:45 PM – 3:00 PM CEST
Location: Room III

    Presenting Author(s)

  • Yanmin Zhu, MS, PhD

    Instructor in Medicine
    Brigham and Women's Hospital and Harvard Medical School
    Boston, United States

    • Co-Author(s)

  • Priyanka Anand, MBBS, MPH

    Research Specialist
    Division of Pharmacoepidemiology and Pharmacoeconomics, Dept of Medicine, Brigham and Women's Hospital
    Chelmsford, United States

  • Ameet Sarpatwari, PhD, JD (he/him/his)

    Assistant Professor of Medicine
    Brigham and Women's Hospital / Harvard Medical School
    Boston, United States

  • Sonia Hernandez-Diaz, MD, DrPH

    Professor of Epidemiology
    Harvard T.H. Chan School of Public Health
    Boston, United States

  • Katsiaryna Bykov, PharmD, ScD

    Assistant Professor
    Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
    Boston, United States

  • Mufaddal Mahesri, MD, MPH (he/him/his)

    Research Scientist
    Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School
    Boston, United States

  • Elyse C. DiCesare, BA

    Research Assistant
    Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, United States

  • HZ

    Heidi Zakoul, BA

    Brigham and Women's Hospital - Division of Pharmacoepidemiology, United States

  • SV

    Seanna Vine

    Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital
    Boston, United States

  • HM

    Helen Mogun

    Brigham and Women's Hospital, United States

  • Gita A. Toyserkani, PharmD, MBA

    Associate Director for Research and Strategic Initiatives
    US Food and Drug Administration
    Silver Spring, United States

  • CL

    Cynthia LaCivita, PharmD

    Director Division of RIsk Managment
    US Food and Drug Administration
    Silver Spring, United States

  • EZ

    Esther H. Zhou, MD, PhD

    Epidemiologist
    U.S. Food and Drug Administration
    Silver Spring, United States

  • Claudia B. Manzo, PharmD

    Office Director
    FDA
    Silver Spring, United States

  • Gerald J. Dal Pan, MD, MHS

    Medical epidemiologist
    US Food and Drug Administration
    Silver Spring, United States

  • Krista F. Huybrechts, PhD, MS

    Associate Professor of Medicine
    Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School
    Boston, United States

Background: Since 2007, the US Food and Drug Administration (FDA) has had the authority to mandate Risk Evaluation and Mitigation Strategies (REMS) to ensure safe use of drugs including certain teratogenic drugs. However, the impact of such REMS on pregnancy outcomes is not fully understood.

Objectives: To evaluate the impact of REMS on the following drugs: ambrisentan, bosentan, lenalidomide, pomalidomide, thalidomide, and isotretinoin in terms of preventing fetal exposure.

Methods: Using the nationwide Medicaid (2000-2018) and MarketScan (2003-2020) databases, we assembled two cohorts of women aged 14-45 who initiated drugs with REMS for teratogenicity. Patients were considered on treatment from treatment initiation through 30 days after the end of the days’ supply and followed from treatment initiation until pregnancy start, treatment discontinuation, or end of enrollment or available data, whichever occurred first. For each drug, we estimated pregnancy rates with 95% confidence intervals (CIs). For isotretinoin (with adequate sample size), we further estimated hazard ratios (HR) using Cox proportional hazards models and propensity score overlap weights. Analyses were stratified by race/ethnicity categories, socioeconomic status, and urban/rural area, and outcomes of pregnancies (live vs non-live births) were assessed.

Results: We identified < 20 pregnancies among ambrisentan (1,789 treatment episodes) and bosentan (2,833) initiators and < 11 pregnancies among lenalidomide (1,032), pomalidomide (67), and thalidomide (1,671) initiators, corresponding to pregnancy rates from 0 to 11.3 per 1,000 person-years. Pregnancy rates among isotretinoin initiators in Medicaid (43,578) and MarketScan (214,846) were 15.1 (95% CI, 13.3-17.1) and 3.1 (2.8-3.5) per 1,000 person-years, corresponding to adjusted HRs of 0.34 (0.29-0.39) and 0.19 (0.17-0.22) compared to topical retinoids, respectively. In Medicaid, adjusted HRs for isotretinoin vs. topical retinoids were 0.27 (0.21-0.34) in Whites, 0.32 (0.16-0.64) in Asians, 0.36 (0.27-0.48) in Hispanics, and 0.44 (0.32-0.59) in Blacks; HRs did not differ by socioeconomic status or between rural and urban areas. In both databases, approximately 61% of isotretinoin-exposed vs. 30% of topical retinoids-exposed pregnancies ended with non-livebirths (spontaneous abortion: 16% vs. 14% in Medicaid, 23% vs. 17% in MarketScan; terminations: 43% vs. 15% in Medicaid, 34% vs. 10% in MarketScan).

Conclusions: Fetal exposure to ambrisentan, bosentan, lenalidomide, pomalidomide, and thalidomide is very rare. REMS for isotretinoin appears effective in preventing pregnancies but disparities were observed among Medicaid recipients and minority populations.