Postmarketing safety study of pregnancy and neonatal outcomes following gepotidacin use

Pregnant women in the study period (the pregnancy must overlap with commercial availability of gepotidacin, based on the launch date). Pregnancy is identified based on end of pregnancy codes (e.g., spontaneous abortion or delivery) using previously described algorithms.

• Aged 15 to 50 years at delivery.
• For each analysis of interest, pregnancies will be required to meet the continuous enrollment criteria.
• Participants will be required to have at least one outpatient dispensing of gepotidacin or standard-of-care antibiotics (comparator) in the etiologically relevant window, and one International Classification of Diseases, Tenth Revision, Clinical Modification outpatient or inpatient diagnosis code for acute cystitis within 7-days before or after the date of dispensing.
• In sensitivity analyses, the inclusion criteria will be broadened to capture all pregnant women who had at least one dispensation for gepotidacin, regardless of a documented acute cystitis diagnosis or related codes. This sensitivity analysis is intended to assess the robustness of findings to incomplete capture of treatment indication in administrative claims data. Within this broadened gepotidacin-exposed cohort, primary and secondary outcomes will be summarized descriptively among pregnancies exposed to gepotidacin outside the main uncomplicated Urinary Tract Infection (uUTI) cohort, including pregnancies with diagnosis codes for uncomplicated urogenital gonorrhea and pregnancies for which the treatment indication cannot be reliably ascertained. When sample size permits, descriptive results will be presented separately for these groups.

Pregnancies with greater than equal to (>=)1 prescription dispensing of a definite teratogenic medication from 5 half-lives (specific for each teratogen) prior to the Estimated Date of Conception (EDC) through the end of the exposure assessment period will be excluded, as these medications present a known increased risk of adverse pregnancy or birth outcomes and they may be too few to be balanced through modeling. For outcomes with more than one exposure window (e.g., early vs late pregnancy), pregnancies with dispensing of definite teratogenic medication will be excluded through the end of the later exposure window.

• For the comparator group, pregnant women exposed to gepotidacin during the 90 days before the estimated EDC to the end of the etiologically relevant exposure window for MCM, small-for-gestational-age birth, and preterm birth will be excluded. For the comparator group, pregnant women exposed to gepotidacin during the 90 days before the start of the etiologically relevant exposure window for stillbirth and spontaneous abortion will be excluded. This window was selected as a conservative design approach to minimize treatment contamination and false¬ negative classification of recent gepotidacin exposure before cohort entry in claims data. Although gepotidacin has a relatively short half-life, use of a longer exclusion window provides a more robust safeguard against comparator-group contamination from recent gepotidacin treatment. We do not expect this restriction to meaningfully limit the comparator cohort because uUTI is common in pregnancy and comparator antibiotic treatment is expected to remain frequent, resulting in a large reference group. For the gepotidacin-exposed cohort, prior comparator antibiotic exposure before cohort entry will be permitted. This approach is intended to preserve cohort size, as comparator use is expected to be more common prior to gepotidacin use since it is a newly marketed drug.