Efficacy and safety of current treatments for paroxysmal nocturnal hemoglobinuria: A systematic review

Pires, Yara Maria da Silva; Bonetti, Aline F.; Ciecilinsky, Jessica Telma; Souza, Alceu

doi:10.1016/j.clicom.2022.11.002

Cited by 2 publications

(3 citation statements)

References 26 publications

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“…Treatment options for PNH often include supportive care, allogeneic hematopoietic stem cell transplant, and complement inhibitors. The FDA has approved three complement inhibitors to treat PNH in recent years: Eculizumab, in 2007; Ravulizumab, in 2018; and Pegcetacoplan, in 2021. have shown that Ravulizumab and Pegcetacoplan are non-inferior drugs compared to the first standardized treatment in efficacy and safety profile [47]. However, Pegcetacoplan is often overlooked in available CPGs, possibly due to its recent approval and the higher amount of evidence for Eculizumab and Ravulizumab.…”

Section: Discussionmentioning

confidence: 99%

A Critical Appraisal of Clinical Practice Guidelines for Pharmacological Treatments of Paroxysmal Nocturnal Hemoglobinuria

Pires,

Deffert,

Humenhuk

et al. 2023

JABB

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Aims: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare chronic disease characterized by complement-mediated hemolysis, thrombosis, and bone marrow failure. This study aims to identify methodological limitations in Clinical Practice Guidelines (CPG) for the treatment of PNH. Thus, we critically evaluate the guidelines, highlighting relevant recommendations supported by high-quality evidence to improve healthcare strategies. Methodology: A systematic search was carried out in PubMed/MEDLINE, Scopus, Embase, COCHRANE, and TRIP databases. From 1995 initially identified references, 1649 articles underwent title and abstract screening. Twenty-three references were selected for full-text screening. Ultimately, 12 CPGs were included. Four independent reviewers assessed the CPGs’ methodological quality using the instruments “Appraisal of Guidelines for Research and Evaluation II” (AGREE II) and “Recommendation Excellence” (AGREE-REX). Their characteristics, as well as any differences in recommendations, were summarized and compared. Results: Twelve guidelines published from 2011 to 2022 by Spain, Brazil, Mexico, Israel, Canada, Turkey, Scotland, and the United Kingdom were included. The UK’s and Brazil’s CPGs received the highest scores. Overall, the CPGs scored strongly in the domains of “Scope and Purpose” and “Clarity of Presentation” since they addressed fundamental aspects, such as aim, specific health questions, target population, and language. All guidelines presented deficiencies in the “Editorial Independence” in AGREE II, and “Values and Preferences” in AGREE-REX, demonstrating the need for a careful revision and improvement of future versions. Conclusion: We found disparities in the methodological quality of the available CPGs. Despite being extremely important, recommendations on adapting treatment to local policies and further updates that include newly approved medications were absent. Approaches that prioritize the engagement of methodologists and multidisciplinary collaborators may also lead to higher quality CPGs for treating PNH.

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Section: Discussionmentioning

confidence: 99%

A Critical Appraisal of Clinical Practice Guidelines for Pharmacological Treatments of Paroxysmal Nocturnal Hemoglobinuria

Pires,

Deffert,

Humenhuk

et al. 2023

JABB

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“…While several systematic reviews have been conducted previously on complement inhibitors for PNH treatment, [16][17][18] they have focused on individual substances or provided a descriptive review of results from clinical trials. No systematic reviews, including those of ravulizumab, have been conducted.…”

Section: Limitationsmentioning

confidence: 99%

“…While pivotal randomized clinical trials (RCTs) have been conducted to obtain regulatory approval for complement inhibitors, their sample sizes are relatively small, and the comparative efficacy data are restricted to a 26-week randomization period. [11][12][13][14][15] Although several systematic reviews on specific complement inhibitors exist, [16][17][18] a comprehensive analysis of short-and long-term efficacy data for all available treatments using unified criteria is still lacking. Considering that clinical trials of rare diseases have limited sample sizes, a comprehensive approach is required to establish optimal treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of complement inhibitors for patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis

Lee,

Kim

et al. 2023

Therapeutic Advances in Hematology

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Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematological disease. The development of complement inhibitors such as eculizumab, ravulizumab, and pegcetacoplan has revolutionized the management of PNH, leading to improvements in overall survival and quality of life for patients. Objectives: This systematic review aims to provide comprehensive evidence of the efficacy of complement inhibitors in relation to treatment duration. Design: This is a systematic review and meta-analysis. Data sources and methods: A thorough literature search was conducted in MEDLINE, EMBASE, and the Cochrane Library up to 3 May 2022. We included all prospective interventional studies including single-arm trials. The primary outcomes of interest were lactate dehydrogenase (LDH) levels, hemoglobin (Hb) concentrations, transfusion avoidance, and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores. Results: Our study included a total of 27 studies, comprising 5 randomized controlled trials and 11 single-arm trials, with a total of 912 patients with PNH. We stratified the studies according to treatment duration, based on the most frequently reported period of 26 weeks. Our analysis showed that treatment-naïve patients who received complement inhibitors had a pooled estimate of a decrease in LDH levels from baseline by −1462.0 U/L (95% CI: −1735.6 to −1188.5) for treatment ⩽26 weeks and −1696.5 U/L (95% CI: −2122.7 to −1270.2) for treatment >26 weeks. The mean Hb levels were increased by 1.4 g/dL (95% CI: 0.5–2.3) and 1.9 g/dL (95% CI: 0.7−3.1) in each group. Treatment with any complement inhibitor prevented the need for transfusion in at least 50% of patients with PNH in all treatment periods. Clinically meaningful improvements in FACIT-F were observed both before and after 26 weeks, with a pooled estimate of 6.8 (95% CI: 6.0−7.6) and 9.5 (95% CI: 7.0−12.0), respectively. Conclusion: Our findings suggest that complement inhibitors can result in positive treatment outcomes and sustained benefits for patients with PNH.

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Efficacy and safety of current treatments for paroxysmal nocturnal hemoglobinuria: A systematic review

Cited by 2 publications

References 26 publications

A Critical Appraisal of Clinical Practice Guidelines for Pharmacological Treatments of Paroxysmal Nocturnal Hemoglobinuria

A Critical Appraisal of Clinical Practice Guidelines for Pharmacological Treatments of Paroxysmal Nocturnal Hemoglobinuria

Efficacy of complement inhibitors for patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis

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