Summary

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• Ultomiris (ravulizumab-cwvz) is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH), the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA), the treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody positive, and the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive.
• This summary is based on the review of six systematic review(s)/meta-analysis(es). ^[1-6]
• Neuromyelitis Optica Spectrum Disorder (NMOSD): C5 inhibitors significantly reduced the rate of first adjudicated relapse (RR = 0.05, 95% CI 0.01-0.15) and improved Hauser Ambulation Index (MD: -0.79, 95% CI -1.27 to -0.31). There was no significant difference in Expanded Disability Status Scale (MD -0.23, 95% CI -0.54-0.08).
• Atypical Hemolytic Uremic Syndrome (aHUS): Eculizumab and ravulizumab were comparable in efficacy. Soluble complement 5b-9 (sC5b) in urine was identified as a potential biomarker to assess treatment response.
• Paroxysmal Nocturnal Hemoglobinuria (PNH): Complement inhibitors (eculizumab, ravulizumab, pegcetacoplan) showed significant improvements in LDH levels, hemoglobin concentrations, transfusion avoidance, and FACIT-F scores in treatment-naive patients. Both short-term (≤26 weeks) and long-term (>26 weeks) treatments were effective.
• Serious adverse events occurred in 42% of patients treated with terminal complement inhibition for atypical hemolytic uremic syndrome (aHUS), with meningococcal infection reported in two patients treated with eculizumab.
• Safety measures were comparable between C5 inhibitors and placebo in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD).
• Population Types and Subgroup Considerations: Significant improvements were noted in relapse rates and quality of life for NMOSD patients with seropositive anti-aquaporin-4 antibody (AQP4+IgG); aHUS patients with genetic mutations in complement regulatory proteins, especially CFI, MCP, and CFH, had a higher risk of recurrence, and early intervention is crucial; PNH patients showed improvement in key biomarkers across different treatment durations; in MG, both anti-complement and FcRn treatments were effective, with FcRn showing greater short-term QMG score improvement; terminal complement inhibition in aHUS provided favorable outcomes in both adult and pediatric populations, though evidence quality was low.