Safety of Ravulizumab Use in Pregnancy: Insights from a Global Pharmacovigilance Analysis.

Abstract

Introduction: Ravulizumab, a second-generation terminal complement C5 inhibitor (engineered from eculizumab) is approved for the treatment of rare complement-mediated disorders paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis (gMG), and neuromyelitis optica spectrum disorder (NMOSD). While eculizumab has an established pregnancy safety profile across these indications, data on ravulizumab during pregnancy and lactation remain limited. This analysis evaluated pregnancy-related safety and outcomes following ravulizumab exposure using global post-marketing data.

Methods: All globally reported pregnancy cases with ≥ 1 documented ravulizumab dose were identified from the Alexion pharmacovigilance database (December 21, 2018 through December 31, 2025). Descriptive statistics were used to summarize patient demographics, treatment patterns, and pregnancy outcomes.

Results: The 354 pregnancy cases with ≥ 1 dose of ravulizumab exposure that were identified include all reported cases: PNH (n = 160), aHUS (n = 72), no condition reported (n = 45), gMG (n = 38), NMOSD (n = 34), and other (n = 5). Among cases with pregnancy outcome data (n = 106), the ravulizumab exposure included full-pregnancy exposure (17.0%), ravulizumab-to-eculizumab switch during pregnancy (24.5%), and incomplete exposure details reported (58.5%). Pregnancy outcomes included 68 live births (64.2%), 29 spontaneous abortions (27.4%), 3 fetal deaths (2.8%), and 6 elective terminations (5.7%). For a nested subset of 44 post-marketing cases with detailed ravulizumab exposure data, as well as information on pregnancy outcomes (PNH [n = 26], aHUS [n = 10], gMG [n = 3], NMOSD [n = 3], and not reported [n = 2]), live births were reported in 32 cases (72.7%), spontaneous abortions in 11 cases (25.0%), and elective terminations in 1 case (2.3%).

Conclusion: This post-marketing analysis provides real-world insights on ravulizumab exposure during pregnancy and suggests favorable outcomes and no unexpected safety signals similar to eculizumab. The findings may support shared decision-making between prescribers and patients when considering the ravulizumab use during pregnancy. An ongoing global observational ravulizumab pregnancy study will further inform the safety profile (NCT06312644).