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The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies. | LitMetric

AI Article Synopsis

  • This manuscript analyzes the effectiveness of C5 and C1 inhibitors, focusing on their "off-label" uses, and provides quantitative findings from studies up to September 2019.
  • It finds that C5 inhibitors, particularly eculizumab and ravulizumab, are beneficial for conditions like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), while C1 esterase inhibitors showed no effects.
  • The findings suggest that eculizumab also helps with refractory generalized myasthenia gravis crises and reduces acute rejections in kidney transplant recipients, aiming for personalized treatment approaches with these drugs.

Article Abstract

This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common "off-label" (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors ( = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554929PMC
http://dx.doi.org/10.3390/biomedicines8090355DOI Listing

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