Paroxysmal nocturnal hemoglobinuria in children and adults: comparative clinical profile and long-term prognosis

Klimova, Olesya; Dobronravov, Alexey; Rudakova, Tatiana A.; Golubovskaya, Irina K.; Lapina, Alexandra; Ivanova, Maria; Smirnova, Anna G.; Bykova, Tatiana A; Ovechkina, Varvara N.; Osipova, A.A.; Melnychenko, Olena; Гиндина, Т. Л.; Baykov, V. V.; Zubarovskaya, L.S.; Добронравов, В. А.; Afanasiev, Boris

doi:10.24287/1726-1708-2018-17-3-11-21

Cited by 7 publications

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“…В результате развивается дефицит или отсутствие на поверхности клеток крови, связанных GPI-якорем с мембраной клеток ингибиторов комплемента -CD55, блокирующего активацию С3-конвертазы комплемента, и CD59, блокирующего формирование мембраноатакующего комплекса (МАК), что приводит к комплементзависимому лизису эритроцитов, активации тромбоцитов, провоспалительным и протромботическим эффектам [4,5]. Клинические проявления и прогноз ПНГ у взрослых и детей детально охарактеризованы в крупных когортных исследованиях в России [6,7]. В течение многих лет терапевтическая тактика при ПНГ имела ограниченные возможности.…”

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“…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 onset of clinical manifestations of PNH can occur in patients of all ages, but the median age of onset is about 30-40 years [2]. The disease is rare and often misdiagnosed in children [4], with pediatric patients accounting for approximately 5-10% of reported PNH cases [5]. Clinical symptoms and disease burden of PNH vary widely between individuals, and are heavily influenced by the proportion of GPI-AP-deficient cells or clone size [6].…”

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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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Evaluating ravulizumab for the treatment of children and adolescents with paroxysmal nocturnal hemoglobinuria

Yoo

Chonat

2022

Expert Review of Hematology

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Paroxysmal nocturnal hemoglobinuria in children and adults: comparative clinical profile and long-term prognosis

Abstract: п е р с п е к т и в н ы е и с с л е д о в а н и я

Cited by 7 publications

References 13 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

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

Evaluating ravulizumab for the treatment of children and adolescents with paroxysmal nocturnal hemoglobinuria

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