Based on data from real-world experience and the best available evidence, 11 experts from 9 countries in Central Europe have developed consensus recommendations on the use of anticomplement agents in specific populations of patients with paroxysmal nocturnal hemoglobinuria (PNH).
Results of the systematic review have been published in the journal Advances in Therapy.
The use of complement inhibition appears to be the best approach for the management of patients with PNH. To date, 3 complement inhibitors have been approved by the European Medicines Agency (EMA) as targeted therapy for PNH:
- Eculizumab: a humanized monoclonal antibody (mAb) that targets the complement 5 (C5) epitope; approved by the EMA in 2007
- Ravulizumab: a humanized mAb that targets the C5 epitope; approved by the EMA in 2019
- Pegcetacoplan: a cyclic peptide that binds to the complement 3 (C3) inhibitor; approved by the EMA in 2021
Current national and international PNH guidelines do not take into consideration the latest clinical trial evidence. Based on the dearth of evidence-based data on some clinical situations that are encountered in real life, the researchers identified specific patient populations with PNH who might derive benefits from switching to proximal C3 inhibition from terminal C5 inhibition.
Read more about experimental therapies for PNH
Although PNH is typically characterized by the development of intravascular hemolysis, bone marrow failure, and possible thrombosis, not all of these clinical features are observed in all patients, based on individual heterogeneity at presentation. PNH can be grouped into 3 main subtypes:
- Classic PNH (including patients with hemolysis and thrombosis); diagnosed in approximately one-third of individuals with the disease, who appear to benefit the most from treatment with complement pathway inhibitors
- Subclinical PNH: the majority of patients in this group are asymptomatic or exhibit limited symptomatology
- PNH in the setting of another specified bone marrow disorder, such as aplastic anemia or myelodysplastic syndrome
The expert consensus recommendations were created by a group of expert PNH specialists across Central Europe with the use of a Delphi-like process. All recommendations were reviewed to test agreement among the experts. Additionally, literature databases were searched for relevant studies, with 50 articles ultimately reviewed by the experts and included in the consensus recommendations as supporting evidence.
The following consensus recommendations were noted:
- In patients with classic PNH symptoms indicative of high disease activity, treatment with a C5 inhibitor (eculizumab or ravulizumab) is recommended.
- In patients with bone marrow failure who have significant PNH clone size and active hemolysis, treatment with a C5 inhibitor is recommended.
- In patients with subclinical PNH who are asymptomatic, anticomplement treatment is not recommended.
- Patients with PNH can be switched from eculizumab administered 2 times weekly to ravulizumab administered every 8 weeks, at the treating physician’s discretion.
- Because of the rarity of PNH, few clinical studies are available to support switching from C5 inhibition to C3 inhibition in specific patient populations with the disorder.
“Implementation of these recommendations uniformly across [healthcare] institutions will promote the best use of complement inhibition in PNH, and has the potential to positively impact patient outcomes in Central Europe and worldwide,” the researchers concluded.
Bodó I, Amine I, Boban A, et al. Complement inhibition in paroxysmal nocturnal hemoglobinuria (PNH): a systematic review and expert opinion from Central Europe on special patient populations. Adv Ther. Published online April 18, 2023. doi:10.1007/s12325-023-02510-4