P056Oral contraceptive adherence and pregnancy rates in estetrol/drospirenone pooled phase 3 trials

Abstract

<h3>Objectives</h3> To assess the relationship of adherence and pregnancy in participants using an estetrol and drospirenone combined oral contraceptive. <h3>Methods</h3> We pooled data from two parallel, multicenter, open-label, phase 3 trials (US/Canada and Europe/Russia) that enrolled healthy participants aged 16–50 to receive estetrol 15 mg/drospirenone 3 mg in a 24/4 regimen for up to 13 cycles. We limited this efficacy analysis to participants aged 16–35 at screening. Participants reported adherence using paper diaries. We assessed the relationship between number of missed pills and pregnancies in at-risk cycles (≥1 confirmed intercourse and no other contraceptive use) and when pregnancies occurred during product use with test for trend and chi-square analyses as appropriate. <h3>Results</h3> Among 3,027 participants in this analysis, 31 on-treatment pregnancies occurred during 26,455 at-risk cycles of use for an overall Pearl Index of 1.52 (95% CI, 1.04–2.16). Pregnancies occurred in 0.09%, 0.25%, 0.83%, and 1.6% of cycles in which participants reported missing 0 (n=25,613 cycles), 1 (n=405 cycles), 2 (n=121 cycles) and >2 (n=314 cycles) active pills, respectively (p<0.0001). Pregnancy rates ranged from 0-0.21% per cycle with no significant trend by cycle (p=0.45). About half (48.4%) of all pregnancies occurred in the first four cycles, with pregnancies occurring in 0.17% of cycles vs. 0.08% during cycles 5–8 and 0.10% in cycles 9–13 (p=0.07). <h3>Conclusions</h3> Pregnancy occurs more frequently when combined oral contraceptive users report missing pills and exceeds 1% only when >2 pills are missed. A 0.09% pregnancy risk among users reporting no missed pills likely approximates a true method failure rate.