Introduction: Paroxysmal nocturnal haemoglobinuria (PNH) is an uncommon, life-threatening disease, caused by intravascular haemolysis by the complement system complement system: A group of proteins that move freely in the bloodstream. These proteins support (complement) the work of white blood cells by fighting infections. . In this review, we aim to compare the efficacy of the available agents across patient-centred outcomes in complement inhibitor-naive patients.
Methods: Following PRISMA guidelines, a comprehensive literature search was conducted on PubMed, Cochrane CENTRAL and ClinicalTrials.gov for studies published up to 30th May 2025. A frequentist model network meta-analyses were conducted in RStudio (v5.4.1) using a common-effects model.
Results: A total of four randomized controlled trials evaluating four complement inhibitor agents (ravulizumab, crovalimab crovalimab: An experimental complement inhibitor C5 monoclonal antibody. By blocking the cleavage of C5 to C5a and C5b, it is expected to inhibit complement activation, which is the cause of a number of diseases. , eculizumab eculizumab: Eculizumab (Soliris ®) is given as an IV into a vein at the doctor’s office or at a special center. The procedure usually takes about 35 minutes. You will probably get an IV once a week for the first 4 weeks. Starting in the 5th week, you will get a slightly higher dose of Soliris every 2 weeks. … and pegcetacoplan pegcetacoplan: EMPAVELI® is the first PNH treatment that binds to complement protein C3. It was approved by the Food and Drug Administration in May 2021 for treating adult patients with paroxysmal nocturnal hemoglobinuria (PNH). EMPAVELI is given skin (subcutaneously) by using the Empaveli injector or with an… ) were included in this systematic review and network meta-analysis, involving 589 complement inhibitor-naïve adults with PNH. Across outcomes, all active treatments demonstrated benefit compared with placebo placebo: A placebo is an inactive pill, liquid, or powder that has no treatment value. or supportive care supportive care: Care given to improve the quality of life, or comfort, of a person with a chronic illness. Supportive care treats the symptoms rather than the underlying cause of a disease. The goal is to help the patient feel better. Patients with low blood counts may be given blood transfusions as supportive… . In the exploratory network meta-analysis of transfusion avoidance, no consistent statistically significant differences were observed between active treatments, although ravulizumab showed higher odds compared with crovalimab (OR = 2.69, 95% CI: 1.13-6.41; p = 0.0256). For change in FACIT-Fatigue score, all active treatments improved fatigue versus placebo, with some statistically significant differences observed between agents; however, these comparisons were based on indirect evidence from a sparse network.
Conclusion: This study suggests that available complement inhibitors improve key outcomes versus placebo/supportive care in complement inhibitors naive PNH. However, the evidence network is sparse (four trials) and the cross-trial differences limit reliable inference regarding relative efficacy between active agents. Comparative findings should be interpreted as hypothesis-generating.