Introduction: Pregnancy can induce protective immunological changes including complement amplification, which may unmask or worsen complement-mediated conditions such as generalized myasthenia gravis (gMG), neuromyelitis optica spectrum disorder (NMOSD), paroxysmal nocturnal hemoglobinuria (PNH), and atypical hemolytic uremic syndrome (aHUS). To date, eculizumab exposures during pregnancy have not suggested safety concerns, but with limited reported exposures since FDA approval (PNH, 2007; aHUS, 2011; gMG, 2017; NMOSD, 2019), further investigation is needed. Available pregnancy-related safety data for C5ITs will provide further information for clinical decision-making.
Objectives: To report pregnancy-related safety outcomes for eculizumab-treated patients.
Methods: A cumulative analysis of pregnancy outcomes in patients treated with eculizumab (March 16, 2007–April 1, 2024) from the Alexion pharmacovigilance safety database was conducted across approved indications, unknown indications, and off-label use from all sources (clinical trials, postmarketing data, literature, and registries).
Results: Overall, 2043 eculizumab maternal exposures during pregnancy included patients with PNH (n=1095, 54%), aHUS (n=387, 19%), gMG (n=92, 5%), NMOSD (n=32, 2%), and unknown indications/off-label use (n=437, 21%). Among all exposures, 628/2043 (31%) had known outcomes; of these, 382/628 (61%) resulted in live birth and 140/628 (22%) ended in spontaneous abortion.
Summary/Conclusion: Regardless of indication, live birth was the most common outcome with eculizumab exposure; spontaneous abortion rates were aligned with the general US population (15%–20%). Limitations include small proportion of exposures with known outcomes, limited disease-specific data, and selective reporting bias. To address the limitations of pharmacovigilance data, further investigations include exploring pregnancy outcomes with ravulizumab, a long-acting C5IT, in an observational study (currently recruiting; NCT06312644).