Pregnancy outcomes in women receiving eculizumab for the management of paroxysmal nocturnal haemoglobinuria

Manning, James E.; Anderson, Rachel M.; Hill, Anita; Zeidan, Doaa; Ciantar, Etienne

doi:10.1177/1753495x211019899

Cited by 3 publications

(8 citation statements)

References 15 publications

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“… 88 The use of eculizumab in pregnant patients for the management of PNH showed maternal benefits throughout pregnancy with a low rate of maternal complications, largely good pregnancy outcomes, and a high rate of fetal survival. 89 , 90 …”

Section: Discussionmentioning

confidence: 99%

Ravulizumab in Myasthenia Gravis: A Review of the Current Evidence

Vu,

Wiendl,

Katsuno

et al. 2023

NDT

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The terminal complement C5 inhibitor ravulizumab was engineered from the humanized monoclonal antibody eculizumab to have an extended half-life and duration of action. It binds to human terminal complement protein C5, inhibiting its cleavage into C5a and C5b, thus preventing the cascade of events that lead to architectural destruction of the postsynaptic neuromuscular junction membrane by the membrane attack complex, and consequent muscle weakness in patients with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG). The 26-week randomized, placebo-controlled period (RCP) of the phase 3 CHAMPION MG study demonstrated the rapid efficacy of ravulizumab in reducing MG symptoms. Weight-based dosing of ravulizumab every 8 weeks provided sustained efficacy, in terms of patient-reported (Myasthenia Gravis–Activities of Daily Living) and clinician-reported (Quantitative Myasthenia Gravis) endpoints in patients with anti-AChR antibody-positive gMG. Pharmacokinetic and pharmacodynamic analyses showed therapeutic serum ravulizumab concentrations (>175 µg/mL) were achieved immediately after the first dose and were maintained throughout 26 weeks, irrespective of patient body weight; inhibition of serum free C5 was immediate, complete (<0.5 μg/mL), and sustained in all patients. Interim results from the open-label extension (OLE) showed that after 60 weeks, efficacy was maintained in patients continuing on ravulizumab. Rapid and sustained improvements in efficacy, similar to those seen in patients initiating ravulizumab in the RCP, were observed after initiation of ravulizumab treatment in patients who switched from placebo in the RCP to ravulizumab in the OLE. The findings from the RCP and OLE support ravulizumab’s favorable safety profile. In conclusion, ravulizumab has a simple weight-based administration and long dosing interval. Its targeted mechanism of action without generalized immunosuppression is reflected in its rapid onset of symptom improvement, sustained efficacy and good safety profile in the treatment of patients with anti-AChR antibody-positive gMG.

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Section: Discussionmentioning

confidence: 99%

Ravulizumab in Myasthenia Gravis: A Review of the Current Evidence

Vu,

Wiendl,

Katsuno

et al. 2023

NDT

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“…Pregnancy before the introduction of eculizumab was considered to be high risk as increased (postpartum) complement activity and the occurrence of disabling, sometimes disastrous thromboembolic events often lead to miscarriage and increased morbidity and mortality 81 . Even with the availability of eculizumab pregnancies in women with PNH remain a challenge and pregnant PNH patients are best cared for by a multidisciplinary team including obstetricians, hematologists and coagulation specialists 82 …”

Section: C5‐inhibition—success With Consequencesmentioning

confidence: 99%

“…81 Even with the availability of eculizumab pregnancies in women with PNH remain a challenge and pregnant PNH patients are best cared for by a multidisciplinary team including obstetricians, hematologists and coagulation specialists. 82 The excitement that came with the availability of a "targeted therapy" for PNH patients was soon paralleled by observations showing that not all PNH patients benefited from C5i equally. In fact longer follow-up revealed, that only a fraction of patients truly became transfusion free and scaled hemoglobin levels in the range of healthy persons.…”

Section: C5-inhibition-success With Consequencesmentioning

confidence: 99%

Paroxysmal nocturnal hemoglobinuria: Where we stand

Panse

2023

American J Hematol

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For the last 20 years, therapy of paroxysmal nocturnal hemoglobinuria (PNH) relied-up until recently-on antibody based terminal complement inhibitionon. PNH pathophysiology-a mutational defect leading to partial or complete absence of complement-regulatory proteins on blood cells-leads to intravascular hemolysis and consequences such as thrombosis and other sequelae. A plethora of new drugs interfering with the proximal and terminal complement cascade are under recent development and the first "proof-of-pinciple" proximal complement inhibitor targeting C3 has been approved in 2021. "PNH: where we stand" will try to give a brief account on where we came from and where we stand focusing on approved therapeutic options. The associated improvements as well as potential consequences of actual and future treatments as well as their impact on the disease will continue to necessitate academic and scientific focus on improving treatment options as well as on side effects and outcomes relevant to individual patient lives and circumstances in order to develop effective, safe, and available treatment for all hemolytic PNH patients globally.Note: Due to space limitation the author mostly cites reviews and overviews, giving readers the chance to easily find continuative summaries of potentially interesting topics. He therefore does apologize

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“…Consequently, women with PNH have often been advised to avoid pregnancy [ 1 , 6 ]. Additional obstacles to successful pregnancy in women with PNH include the risks for worsening of PNH-related anemia, thromboembolic events, and intravascular hemolysis during pregnancy [ 7 ], with thromboembolic risks extending into the postpartum period [ 3 ]. Fortunately, data are becoming available suggesting that eculizumab, the first complement component 5 (C5) inhibitor approved for patients with PNH [ 8 ], can improve pregnancy outcomes for women with PNH and their infants [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

“…Additional obstacles to successful pregnancy in women with PNH include the risks for worsening of PNH-related anemia, thromboembolic events, and intravascular hemolysis during pregnancy [ 7 ], with thromboembolic risks extending into the postpartum period [ 3 ]. Fortunately, data are becoming available suggesting that eculizumab, the first complement component 5 (C5) inhibitor approved for patients with PNH [ 8 ], can improve pregnancy outcomes for women with PNH and their infants [ 6 , 7 ]. There are no reports of pregnancy outcomes for women with PNH treated with the next-generation C5 inhibitor ravulizumab, which was approved for the treatment of PNH in 2018 [ 2 , 9 ].…”

Section: Introductionmentioning

confidence: 99%