Consenso español para el diagnóstico y tratamiento de la hemoglobinuria paroxística nocturna

Villegas, Ana; Arrizabalaga, Beatriz; Bonanad, Santiago; Colado, Enrique; González, Antonio; Jarque, Isidro; Núñez, Ramiro; Ojeda, Emilio; Órfão, Alberto; Ribera, Josep‐Marǐa; Vicente, Vicente; Urbano-Ispizúa, Álvaro

doi:10.1016/j.medcli.2015.12.012

Cited by 16 publications

(13 citation statements)

References 23 publications

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“…Прорывом в лечении стало применение патогенетической терапии моноклональным антителом экулизумаб, блокирующим белок комплемента С5. В настоящее время патогенетическая антикомплементарная терапия и трансплантация аллогенного костного мозга являются основными эффективными методами лечения классической ПНГ [1,2,8].…”

Section: ââåäåíèåunclassified

“…Samara State Medical University, Samara, Russia; 5 Sverdlovsk Regional Clinical Hospital №1, Yekaterinburg, Russia; 6 Rostov Regional Clinical Hospital, Rostov-on-Don, Russia; 7 Kirov Research Institute of Hematology and Blood Transfusion, Kirov, Russia; 8 JSC GENERIUM, Moscow, Russia Currently, the main pathogenetic method for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) is the treatment with recombinant monoclonal antibodies that block the C5 component of the complement system. Eculizumab is the first biotechnological drug, which is a monoclonal antibody, with proven clinical efficacy and safety for the treatment of patients with PNH, which is used in world clinical practice.…”

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Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy

Птушкин

Lukina²,

Давыдкин

et al. 2020

Terapevticheskii arkhiv

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Currently, the main pathogenetic method for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) is the treatment with recombinant monoclonal antibodies that block the C5 component of the complement system. Eculizumab is the first biotechnological drug, which is a monoclonal antibody, with proven clinical efficacy and safety for the treatment of patients with PNH, which is used in world clinical practice. In Russia, in the framework of the state program Development of the pharmaceutical and medical industry for 20132020 was developed Elizaria (JSC GENERIUM) the first biosimilar of the original drug eculizumab. Aim.To evaluate the pharmacokinetic and pharmacodynamic parameters, as well as safety and immunogenicity parameters of the drug Elizara in the induction phase of therapy in previously untreated patients with PNH. Materials and methods.The study included 11 patients with PNH aged 26 to 75 years who had not previously received eculizumab. Each of the study participants was injected with the studied drug Elizaria at a dose of 600 mg intravenously once a week for 4 weeks. Results.During the clinical study, it was noted that the concentration of the studied drug significantly increased by the time the infusion was completed and then gradually decreased to a minimum at the end of the dosing interval. The average concentration of eculizumab 5 minutes before the administration of the study drug at all visits exceeded 35 g/ml, the minimum concentration sufficient to completely inhibit intravascular hemolysis in patients with PNH. The pharmacodynamic efficacy of the drug Elizaria was confirmed by a decrease in the concentration of the membrane-attack complex (MAC) after the first infusion of the drug was maintained at stable levels until visit 5. A persistent decrease in the level of MAC and a four-fold decrease in the average values of lactate dehydrogenase to visit 5 from 1286.4 to 280.9 U/l demonstrated a marked decrease in activity and stabilization of the hemolytic process against the background of the induction of therapy with Elizaria at a dose of 600 mg once a week and confirmed the effecacy of the study drug. Among the 9 adverse events, only 5 had a relationship with the studied drug, including one serious adverse event in the form of an allergic reaction, which, according to the researcher, had a possible cause-effect relationship with the infusion of the studied drug. In 2 patients, low-titer binding anti-drug antibodies were detected without neutralizing activity during treatment with the studied drug, which may indicate its low immunogenicity. Conclusion.The study evaluated the pharmacokinetic and pharmacodynamic properties of the drug Elizaria in the regimen of induction therapy in previously untreated patients with PNH, confirming its efficacy. The study demonstrated the safety and low immunogenicity of the study drug.

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confidence: 99%

Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy

Птушкин

Lukina²,

Давыдкин

et al. 2020

Terapevticheskii arkhiv

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“…The treatment with erythropoietin is suggested by three guidelines only (Parker et al, 2005;Lazarowski et al, 2013;Weitz, 2017). All but one (Weitz, 2017) guideline recommend folic acid or iron supplementation and two guidelines do not recommend (Sahin et al, 2016) or do not mention (Villegas et al, 2016) iron supplementation.…”

Section: Supportive Treatmentmentioning

confidence: 99%

“…The specificity of the indications cited in the guidelines ranged from the treatment of classical PNH to very specific indications, as presented in Table 2. Regarding dosage, all guidelines that mention the protocol of treatment are unanimous in indicating 600 mg per week in the first 4 weeks, 900 mg in the 5th week and then continuing with a 900 mg dose every 2 weeks (Villegas et al, 2016;Sahin et al, 2016;Schubert et al, 2012;Australian Government. Department of Health and Ageing, 2010;Weitz, 2017).…”

Section: Disease-modifying Treatmentsmentioning

confidence: 99%

“…The deficiency of two glycosylphosphatidylinositol-anchored proteins (GPI-APs), CD55 and CD59, leads to red blood cell susceptibility to complement that accounts for hemolysis and is implicated in the tendency for patients to have thromboses (Hillmen et al, 1995;Brodsky, 2014). A somatic mutation in the X-linked phosphatidyl-inositol glycan class A (PIG-A) gene in patients with PNH impairs the encoding of the subunit A of phosphatidylinositol N-acetylglucosaminyltransferase, one of the enzymes required for the synthesis of GPI anchors (Hill et al, 2013;Villegas et al, 2016) The diagnosis of PNH is currently made by flow cytometry studies demonstrating the presence of peripheral blood cells with absence of at least two cell surface markers anchored by GPI (Villegas et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Current global scenario of guidelines on the management of paroxysmal nocturnal hemoglobinuria: a systematic literature review

Soares¹,

Fonseca²,

Fertrin³

et al. 2020

JBES

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Objective: To report the outcomes of a systematic literature review of guidelines and consensus on the management of paroxysmal nocturnal hemoglobinuria (PNH) and describe the main therapeutic options available worldwide. Methods: A systematic literature review was conducted in April 2018 with no time limit and reported in line with the PRISMA statement. The AGREE II instrument was used to determine the quality of each guideline included in the systematic review. Results: Eight guidelines/consensus were eligible, one developed by an international group, two in Spain, and one each in Turkey, Germany, Argentina, Australia and the United Kingdom. Supportive treatment with erythrocyte transfusion, anticoagulants and steroids is indicated by all guidelines and consensus. The use of erythropoietin is suggested by three of them. Recommendations for the prescription of eculizumab were consistent in all but one guideline, published in 2005. Allogeneic hematopoietic stem cell transplantation is reported as the only potentially curative treatment for PNH, although its association with high mortality and morbidity rates is emphasized, being indicated for a selected group of patients. The AGREE II scores applied for each domain showed in general a low and heterogeneous methodological quality among guidelines. Conclusion: Despite the low and heterogeneous methodological quality, in general the comparison of guidelines and consensus for PNH management showed consistent recommendations regarding supportive care, eculizumab and hematopoietic stem cell transplantation.

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Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Expert Opinion from Central Europe on Special Patient Populations

et al. 2023

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Introduction Hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) is complement-mediated due to the lack of complement inhibitors in the hemopoietic cell membranes, making complement inhibition the best approach to manage PNH. Three complement inhibitors are approved by the European Medicines Agency as targeted therapy for PNH: eculizumab and ravulizumab, two humanized monoclonal antibodies targeting the same complement 5 (C5) epitope, approved in 2007 and 2019, respectively, and the more recently approved cyclic peptide, the complement 3 (C3) inhibitor pegcetacoplan. Although national and international PNH treatment guidelines exist, they do not take into consideration the latest clinical trial evidence. Given the lack of evidence-based data for some clinical situations encountered in real life, we identified specific populations of patients who may benefit from switching to proximal C3 from terminal C5 inhibition. Methods The expert recommendations presented here were created using a Delphi-like process by a group of expert PNH specialists across Central Europe. Based on an initial advisory board meeting discussion, recommendations were prepared and reviewed as part of a Delphi survey to test agreement. Results Using a systematic approach, literature databases were searched for relevant studies, and 50 articles were reviewed by the experts and included as supporting evidence. Conclusion Implementation of these recommendations uniformly across healthcare institutions will promote the best use of complement inhibition in managing PNH, and has the potential to positively impact patient outcomes in Central Europe and worldwide. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02510-4.

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Consenso español para el diagnóstico y tratamiento de la hemoglobinuria paroxística nocturna

Cited by 16 publications

References 23 publications

Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy

Results of phase Ib open multicenter clinical trial of the safety, pharmacokinetics and pharmacodynamics of first biosimilar of eculizumab in untreated patients with paroxysmal nocturnal hemoglobinuria during induction of therapy

Current global scenario of guidelines on the management of paroxysmal nocturnal hemoglobinuria: a systematic literature review

Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Expert Opinion from Central Europe on Special Patient Populations

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