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
Coralina Bernuy-Guevara,
Hassib Chehade,
Yannick D. Muller,
Julien Vionnet,
François Cachat,
Gabriella Guzzo,
Carlos Ochoa-Sangrador,
F. Javier Álvarez,
Daniel Teta,
Débora Martín-García,
Marcel Adler,
Félix J. de Paz,
Frank Lizaraso-Soto,
Manuel Pascual,
Francisco Herrera-Gómez
Affiliations
Coralina Bernuy-Guevara
Pharmacological Big Data Laboratory, University of Valladolid, 47005 Valladolid, Spain
Hassib Chehade
Pediatric Nephrology Unit, Lausanne University Hospital and University of Lausanne, 1100 Lausanne, Switzerland
Yannick D. Muller
Transplantation Center, Lausanne University Hospital and University of Lausanne, 1100 Lausanne, Switzerland
Julien Vionnet
Transplantation Center, Lausanne University Hospital and University of Lausanne, 1100 Lausanne, Switzerland
François Cachat
Pediatric Nephrology Unit, Lausanne University Hospital and University of Lausanne, 1100 Lausanne, Switzerland
Gabriella Guzzo
Transplantation Center, Lausanne University Hospital and University of Lausanne, 1100 Lausanne, Switzerland
Carlos Ochoa-Sangrador
Clinical Epidemiology Support Office, Sanidad de Castilla y León, 49022 Zamora, Spain
F. Javier Álvarez
Pharmacological Big Data Laboratory, University of Valladolid, 47005 Valladolid, Spain
Daniel Teta
Department of Nephrology, Hôpital du Valais, 1950 Sion, Switzerland
Débora Martín-García
Clinical Nephrology Unit, University Clinical Hospital of Valladolid, 47003 Valladolid, Spain
Marcel Adler
Center for Medical Oncology & Hematology, Hospital Thun, 3600 Thun, Switzerland
Félix J. de Paz
Pharmacological Big Data Laboratory, University of Valladolid, 47005 Valladolid, Spain
Frank Lizaraso-Soto
Pharmacological Big Data Laboratory, University of Valladolid, 47005 Valladolid, Spain
Manuel Pascual
Transplantation Center, Lausanne University Hospital and University of Lausanne, 1100 Lausanne, Switzerland
Francisco Herrera-Gómez
Pharmacological Big Data Laboratory, University of Valladolid, 47005 Valladolid, Spain
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.
