RT info:eu-repo/semantics/article T1 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 A1 Bernuy Guevara, Coralina Melissa A1 Chehade, Hassib A1 Muller, Yannick D. A1 Vionnet, Julien A1 Cachat, François A1 Guzzo, Gabriella A1 Ochoa Sangrador, Carlos A1 Álvarez González, Francisco Javier A1 Teta, Daniel A1 Martín García, Débora A1 Adler, Marcel A1 Paz Fernández, Félix Jesús de A1 Lizaraso Soto, Frank A1 Pascual, Manuel A1 Herrera Gómez, Francisco Magno K1 Meta-analysis K1 Biological products - Analysis K1 Productos biológicos K1 Complement inactivating K1 Agents K1 3209 Farmacología AB 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 (n = 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. PB MDPI SN 2227-9059 YR 2020 FD 2020 LK https://uvadoc.uva.es/handle/10324/59002 UL https://uvadoc.uva.es/handle/10324/59002 LA eng NO Biomedicines, 2020, Vol. 8, Nº. 9, 355 NO Producción Científica DS UVaDOC RD 24-nov-2024