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A randomized, placebo-controlled trial of canakinumab in patients with peripheral artery disease.
Vasc Med 2019; :1358863X19859072VM

Abstract

Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1β (IL-1β) may play an important pro-inflammatory role in the pathogenesis of this disease. Interruption of IL-1β signaling was hypothesized to decrease plaque progression in the leg macrovasculature and improve the mobility of patients with PAD with intermittent claudication. Thirty-eight patients (mean age 65 years; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. The mean vessel wall area (by 3.0 T black-blood magnetic resonance imaging (MRI)) of the superficial femoral artery (SFA) was used to measure plaque volume. Mobility was assessed using the 6-minute walk test. Canakinumab was safe and well tolerated. Markers of systemic inflammation (interleukin-6 and high-sensitivity C-reactive protein) fell as early as 1 month after treatment. MRI (32 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA in either placebo-treated or canakinumab-treated patients. Although an exploratory endpoint, placebo-adjusted maximum and pain-free walking distance (58 m) improved as early as 3 months after treatment with canakinumab when compared with placebo. Although canakinumab did not alter plaque progression in the SFA, there is an early signal that it may improve maximum and pain-free walking distance in patients with symptomatic PAD. Larger studies aimed at this endpoint will be required to definitively demonstrate this. ClinicalTrials.gov Identifier: NCT01731990.

Authors+Show Affiliations

1 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.1 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.2 University of Virginia Health System, Charlottesville, VA, USA.1 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.1 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.1 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.1 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.1 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.3 Remington-Davis Clinical Research, Columbus, OH, USA.4 Jacksonville Center for Clinical Research, Jacksonville, FL, USA.5 Praxis für Herzkreislauferkrankungen, Max Grundig Klinik Bühlerhöhe, Bühl, Germany.6 Triumpharma, Ammann, Jordan.7 River City Research, Jacksonville, FL, USA.8 Asklepios Klinik Sankt Georg, Hamburg, Germany.9 University of Tennessee, VRG/NOCCR, Knoxville, TN, USA.10 University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.11 Johns Hopkins Medicine, Baltimore, MD, USA.1 Novartis Institutes for BioMedical Research, Cambridge, MA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31277561

Citation

Russell, Kerry S., et al. "A Randomized, Placebo-controlled Trial of Canakinumab in Patients With Peripheral Artery Disease." Vascular Medicine (London, England), 2019, p. 1358863X19859072.
Russell KS, Yates DP, Kramer CM, et al. A randomized, placebo-controlled trial of canakinumab in patients with peripheral artery disease. Vasc Med. 2019.
Russell, K. S., Yates, D. P., Kramer, C. M., Feller, A., Mahling, P., Colin, L., ... Basson, C. T. (2019). A randomized, placebo-controlled trial of canakinumab in patients with peripheral artery disease. Vascular Medicine (London, England), p. 1358863X19859072. doi:10.1177/1358863X19859072.
Russell KS, et al. A Randomized, Placebo-controlled Trial of Canakinumab in Patients With Peripheral Artery Disease. Vasc Med. 2019 Jul 5;1358863X19859072. PubMed PMID: 31277561.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomized, placebo-controlled trial of canakinumab in patients with peripheral artery disease. AU - Russell,Kerry S, AU - Yates,Denise P, AU - Kramer,Christopher M, AU - Feller,Andrea, AU - Mahling,Ping, AU - Colin,Laurence, AU - Clough,Timothy, AU - Wang,Tianke, AU - LaPerna,Lucy, AU - Patel,Alpa, AU - Lawall,Holger, AU - Shennak,Mustafa M, AU - Fulmer,James, AU - Nikol,Sigrid, AU - Smith,William B, AU - Müller,Oliver J, AU - Ratchford,Elizabeth V, AU - Basson,Craig T, Y1 - 2019/07/05/ PY - 2019/7/7/entrez KW - canakinumab KW - interleukin-1β KW - intermittent claudication KW - peripheral artery disease (PAD) SP - 1358863X19859072 EP - 1358863X19859072 JF - Vascular medicine (London, England) JO - Vasc Med N2 - Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1β (IL-1β) may play an important pro-inflammatory role in the pathogenesis of this disease. Interruption of IL-1β signaling was hypothesized to decrease plaque progression in the leg macrovasculature and improve the mobility of patients with PAD with intermittent claudication. Thirty-eight patients (mean age 65 years; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. The mean vessel wall area (by 3.0 T black-blood magnetic resonance imaging (MRI)) of the superficial femoral artery (SFA) was used to measure plaque volume. Mobility was assessed using the 6-minute walk test. Canakinumab was safe and well tolerated. Markers of systemic inflammation (interleukin-6 and high-sensitivity C-reactive protein) fell as early as 1 month after treatment. MRI (32 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA in either placebo-treated or canakinumab-treated patients. Although an exploratory endpoint, placebo-adjusted maximum and pain-free walking distance (58 m) improved as early as 3 months after treatment with canakinumab when compared with placebo. Although canakinumab did not alter plaque progression in the SFA, there is an early signal that it may improve maximum and pain-free walking distance in patients with symptomatic PAD. Larger studies aimed at this endpoint will be required to definitively demonstrate this. ClinicalTrials.gov Identifier: NCT01731990. SN - 1477-0377 UR - https://www.unboundmedicine.com/medline/citation/31277561/A_randomized,_placebo-controlled_trial_of_canakinumab_in_patients_with_peripheral_artery_disease L2 - http://journals.sagepub.com/doi/full/10.1177/1358863X19859072?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -