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Background Atypical hemolytic uremic syndrome (aHUS) triggered by pregnancy is a rare disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor obtained through selective modifications to eculizumab, is efficacious in inhibiting complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. In this analysis, we report outcomes in a subgroup of patients from the 311 study who developed TMA postpartum. Methods This was a phase 3, multicenter trial evaluating efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete TMA response (simultaneous platelet count normalization [≥150 × 109/L], lactate dehydrogenase normalization [≤246 U/L] and 25% improvement in serum creatinine) through the 183-day initial evaluation period. Additional efficacy endpoints included time to complete TMA response, hematologic normalization, and dialysis requirement status. Results Eight patients presenting with TMA postpartum (median age of 37.7 [range; 22.1–45.2] years) were diagnosed with aHUS and received ≥1 dose of ravulizumab. Five patients (63%) were on dialysis at baseline. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 31.5 days. Hematologic normalization was observed in all patients. All patients on dialysis at baseline discontinued dialysis within 21 days after treatment with ravulizumab. All patients showed continued improvements in the estimated glomerular filtration rate from baseline to Day 183. Three possible treatment-related adverse events were observed in 2 patients (arthralgia and nasopharyngitis [both non-severe]; urinary tract infection). No deaths or meningococcal infections occurred. Conclusions Treatment with ravulizumab provided immediate and complete C5 inhibition, resulting in rapid clinical and laboratory improvements and complete TMA response through 183 days in patients with aHUS triggered by pregnancy. The safety profile observed in this subset of patients analysed is consistent with the 311 study investigating ravulizumab in patients with aHUS naïve to complement treatment. Trial registration Clinical trial identifier:NCT02949128.

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Background Myeloproliferative diseases (MPD) rarely occur in women of reproductive age. But in recent years it becomes more often that young women suffer from these diseases. The development of new drugs and therapeutic strategies provides good results in survival rate and life prognosis for these patients. All this requires special options for management of pregnancy in women with MPD. Aims To develop the protocol of preconception planning and pregnancy management and to evaluate pregnancy outcomes and complications in women with MPD. Methods We have analyzed 110 pregnancies in 90 women. The prospective group (group 1) included 67 women who were treated according to our algorithm. Retrospectively we have analyzed 43pregnancies in 23 women (group 2) who did not receive a special treatment of MPD during pregnancy. Our trial included women with main MPD: essential thrombocythemia, polycythemia vera, primary myelofibrosis. Pregnancy management included examination of blood cell count and hemostasis system twice a month, besides this the inherited trombophylia testing, lupus anticoagulant, homocystein level, antiphospholipid syndrome diagnostics and hematologic examination including trepanobiopsy and JAK2V617F mutation. Besides thorough laboratory examination our algorithm of pregnancy planning and management included cytoreductive therapy, antiaggregants, low molecular weight heparin, plasmapheresis, vitamins of group B. For the cytoreductive therapy we prescribed Interferon alfa which is the safest option in preconception planning and pregnancy management for women with MPD. Results Termination of pregnancy was made in 2 (3%) women of group 1 and in 3 (6,9%) women of group 2 (OR – 2,44; 95% C.I.: 0,265; 30,109). In the group of women who were treated according to our algorithm 6% of women (4 pregnancies) developed spontaneous abortions. In group 2 without special treatment spontaneous miscarriages occurred in 62,8% in comparison with group 1 (OR – 16,88; 95% C.I.: 4,655; 74,177). First and second trimester spontaneous abortions in group 2 prevailed among all the miscarriages – 15 (34,9%) cases, stillbirth occurred in 12 (27,9%) cases. Preterm labor were in 5 (7,4%) and 6 (14%) pregnancies in 1 and 2 groups respectively (OR – 2,01; 95% C.I.: 0,471; 8,899). Full-term delivery occurred in 83,6% (56 pregnancies) and 16,3% of cases (7 pregnancies) in two groups (OR – 26,18; 95% C.I.: 8,441; 85,448). Complications of pregnancy were analysed in 61 and 13 women in 1 and 2 groups respectively. Pregnancy was uncomplicated in 21 (34,4%) and 2 (15,4%) cases in 1 and 2 groups respectively (OR – 2,89; 95% C.I.: 0,544; 28,852). The most often pregnancy complications were threatening miscarriage - 25 (41%) and 10 (76,9%) cases (OR – 0,21; 95% C.I.: 0,034; 0,937), anemia – 22 (36%) and 4 (30,8%) cases in 1 and 2 groups respectively (OR – 1,27; 95% C.I.: 0,307; 6,289). Although all pregnancies in group 1 were carefully observed and treated 14,8% of them (9 pregnancies) were complicated by placental isufficiency with IUGR in 5 (8,2%) cases. Placental insufficiency complicated 30,8% pregnancies (4 cases) including intrauterine growth retardation (IUGR) in 2 cases in group 2 (OR – 0,95; 95% C.I.: 0,161; 10,263). Conclusion Thus pregnancy losses in women suffering from MPD occur in 62,8% without special treatment and complications of pregnancy – in 84,6% cases. The development of algorithm for preconception planning and pregnancy management resulted in considerable decrease in miscarriages to 6% (P<0,001) and reduction of pregnancy complications to 65,6% (P=0,3). Disclosures: No relevant conflicts of interest to declare.