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Cited by 914Hemoglobinopathies and Related DisordersBlood groups and transfusionHemophilia Treatment and Research

Crizanlizumab for the prevention of pain crises in sickle cell disease.

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Ataga, Kenneth I., Kutlar, Abdullah, Kanter, Julie, Liles, Darla, Cancado, Rodolfo, Friedrisch, João, Guthrie, Troy H., Knight-Madden, Jennifer +8 more·2017·New England Journal of Medicine
DOI 10.1056/nejmoa1611770PMC PMC5481200
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Abstract

BACKGROUND: The up-regulation of P-selectin in endothelial cells and platelets contributes to the cell-cell interactions that are involved in the pathogenesis of vaso-occlusion and sickle cell-related pain crises. The safety and efficacy of crizanlizumab, an antibody against the adhesion molecule P-selectin, were evaluated in patients with sickle cell disease. METHODS: In this double-blind, randomized, placebo-controlled, phase 2 trial, we assigned patients to receive low-dose crizanlizumab (2.5 mg per kilogram of body weight), high-dose crizanlizumab (5.0 mg per kilogram), or placebo, administered intravenously 14 times over a period of 52 weeks. Patients who were receiving concomitant hydroxyurea as well as those not receiving hydroxyurea were included in the study. The primary end point was the annual rate of sickle cell-related pain crises with high-dose crizanlizumab versus placebo. The annual rate of days hospitalized, the times to first and second crises, annual rates of uncomplicated crises (defined as crises other than the acute chest syndrome, hepatic sequestration, splenic sequestration, or priapism) and the acute chest syndrome, and patient-reported outcomes were also assessed. RESULTS: A total of 198 patients underwent randomization at 60 sites. The median rate of crises per year was 1.63 with high-dose crizanlizumab versus 2.98 with placebo (indicating a 45.3% lower rate with high-dose crizanlizumab, P=0.01). The median time to the first crisis was significantly longer with high-dose crizanlizumab than with placebo (4.07 vs. 1.38 months, P=0.001), as was the median time to the second crisis (10.32 vs. 5.09 months, P=0.02). The median rate of uncomplicated crises per year was 1.08 with high-dose crizanlizumab, as compared with 2.91 with placebo (indicating a 62.9% lower rate with high-dose crizanlizumab, P=0.02). Adverse events that occurred in 10% or more of the patients in either active-treatment group and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. CONCLUSIONS: In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events. (Funded by Selexys Pharmaceuticals and others; SUSTAIN ClinicalTrials.gov number, NCT01895361 .).

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  • Crizanlizumab reduced vaso-occlusive episodes in SCD.

    “Recently approved therapies, including luspatercept 9 and crizanlizumab, 10 have reduced transfusion requirements in patients with TDT and the incidence of vaso-occlusive episodes in those with SCD, respectively, but neither treatment addresses the underlying cause of the disease nor fully ameliorates disease manifestations.”

    From CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia (2021) · cites this paper as [10]

  • Neither luspatercept nor crizanlizumab addresses the underlying cause or fully ameliorates disease.

    “Recently approved therapies, including luspatercept 9 and crizanlizumab, 10 have reduced transfusion requirements in patients with TDT and the incidence of vaso-occlusive episodes in those with SCD, respectively, but neither treatment addresses the underlying cause of the disease nor fully ameliorates disease manifestations.”

    From CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia (2021) · cites this paper as [10]

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Authors
Ataga, K. I., Kutlar, A., Kanter, J., Liles, D., Cancado, R., Friedrisch, J., Guthrie, T. H., Knight-Madden, J., Alvarez, O. A., Gordeuk, V. R., Gualandro, S., Colella, M. P., Smith, W. R., Rollins, S. A., Stocker, J. W., & Rother, R. P.
Affiliations
University of North Carolina at Chapel Hill (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2017-02-02
Volume
376
Issue
5
Pages
429-439
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa1611770
PMC
PMC5481200
OpenAlex
W2559643145
Cited by
914
References
28
Citations by year
2026: 81 · 2025: 89 · 2024: 108 · 2023: 111 · 2022: 136 · 2021: 120 · 2020: 102 · 2019: 68 · 2018: 55 · 2017: 41 · 2016: 1
FWCI
39.90
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • New England Journal of Medicine (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • University of North Florida Digital Commons (University of North Florida) (submittedVersion)
Funders
  • U.S. Food and Drug Administration (R01 FD004805)
  • National Heart, Lung, and Blood Institute (R44HL093893)
Topics
  • Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
  • Health Sciences › Medicine › Hematology › Blood groups and transfusion
  • Health Sciences › Medicine › Hematology › Hemophilia Treatment and Research
Keywords
crizanlizumab, sickle cell disease, vaso-occlusive crisis, P-selectin, vascular occlusion, acute chest syndrome, hydroxyurea, monoclonal antibody therapy, hospitalization, patient-reported outcomes, adverse events, priapism, hepatic sequestration, splenic sequestration, endothelial cell adhesion, platelet adhesion, disease-modifying therapy
MeSH terms
Adolescent, Adult, Anemia, Sickle Cell, Antibodies, Monoclonal, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Hydroxyurea, Male, Middle Aged, Pain, Quality of Life, P-Selectin, Young Adult, Antibodies, Monoclonal, Humanized

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