Ruxolitinib versus standard therapy for the treatment of polycythemia vera
Open accessAbstract
BACKGROUND: Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea. METHODS: We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging. RESULTS: The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two groups, respectively, had at least a 35% reduction in spleen volume. A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P=0.003); 49% versus 5% had at least a 50% reduction in the total symptom score at week 32. In the ruxolitinib group, grade 3 or 4 anemia occurred in 2% of patients, and grade 3 or 4 thrombocytopenia occurred in 5%; the corresponding percentages in the standard-therapy group were 0% and 4%. Herpes zoster infection was reported in 6% of patients in the ruxolitinib group and 0% of those in the standard-therapy group (grade 1 or 2 in all cases). Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving standard therapy. CONCLUSIONS: In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera. (Funded by Incyte and others; RESPONSE ClinicalTrials.gov number, NCT01243944.).
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Ruxolitinib has been internationally approved for therapy of myelofibrosis and polycythemia vera, which are frequently caused by the V617F gain-of-function mutation within JAK2.
“The JAK1/2 inhibitor Ruxolitinib/INCB018424 (Jakavi/Jakafi, Incyte Pharmaceuticals, Novartis; Lin et al., 2009; Quintas-Cardama et al., 2010) has been internationally approved for the therapy of myelofibrosis (Mesa et al., 2012; Verstovsek et al., 2012) and polycythemia vera (Vannucchi et al., 2015), which are frequently caused by the V617F gain-of-function mutation within JAK2 (Kralovics et al.,”
From Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib (2017) · cites this paper as Vannucchi et al., 2015
The Abstract Background and Discussion report that ruxolitinib was studied and found effective for polycythemia vera, the condition for which this citation is offered. Our copy does not establish the claimed international approval; it describes the study as taking place when there were no approved alternatives for these patients. The myelofibrosis and JAK2-mutation portions are attached to other citations. (LLM, conf=0.83)
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“Treatment with the JAK1/2 inhibitor ruxolitinib resulted in clinical improvements in polycythemia vera and an increased survival in primary myelofibrosis.(32,33) Because”
BackgroundInflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms
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“The pivotal COMFORT-II study in myelofibrosis patients has been co-ordinated and performed in Europe;(124) the international pivotal RESPONSE study in PV has been co-ordinated and largely carried out in Europe as well.(125) European researchers first discovered genetic haplotypes predisposing to MPNs and highlighted t…”
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“, 2012) and polycythemia vera (Vannucchi et al., 2015), which are frequently caused by the V617F gain-of-function mutation within JAK2 (Kralovics et al.”
Background
- Authors
- Vannucchi, A. M., Kiladjian, J. J., Griesshammer, M., Masszi, T., Durrant, S., Passamonti, F., Harrison, C. N., Pane, F., Zachee, P., Mesa, R., He, S., Jones, M. M., Garrett, W., Li, J., Pirron, U., Habr, D., & Verstovsek, S.
- Affiliations
- Semmelweis University (HU)
- Hôpital Saint-Louis (FR)
- Johannes Wesling Klinikum Minden (DE)
- Royal Brisbane and Women's Hospital (AU)
- Ospedale di Circolo e Fondazione Macchi (IT)
- Guy's and St Thomas' NHS Foundation Trust (GB)
- University of Naples Federico II (IT)
- Mayo Clinic (US)
- Incyte (United States) (US)
- Novartis (Switzerland) (CH)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2015-01-29
- Volume
- 372
- Issue
- 5
- Pages
- 426-435
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC4358820
- OpenAlex
- W2122395736
- Cited by
- 891
- References
- 0
- Citations by year
- 2026: 42 · 2025: 48 · 2024: 59 · 2023: 77 · 2022: 72 · 2021: 100 · 2020: 88 · 2019: 79 · 2018: 89 · 2017: 82 · 2016: 81 · 2015: 70 · 2014: 2
- FWCI
- 60.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Florence Research (University of Florence) (submittedVersion)
- IrInSubria (University of Insubria) (submittedVersion)
- Funders
- National Cancer Institute (CA 016672, P30CA016672)
- Topics
- Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Emergency Medicine › Hematological disorders and diagnostics
- Keywords
- ruxolitinib, polycythemia vera, JAK inhibitors, hydroxyurea, phlebotomy, splenomegaly, hematocrit control, spleen volume reduction, hematologic remission, anemia, thrombocytopenia, herpes zoster, thromboembolic events, treatment efficacy and safety, myeloproliferative neoplasms
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Blood Cell Count, Female, Humans, Hydroxyurea, Male, Middle Aged, Nitriles, Organ Size, Polycythemia Vera, Pyrazoles, Pyrimidines, Remission Induction, Spleen, Thrombocytopenia, Kaplan-Meier Estimate, Janus Kinases
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