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Canakinumab does not affect vascular function, structure
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In a new study, treatment with the interleukin-1 inhibitor canakinumab had no significant effect on vascular function or structure compared with placebo in patients with atherosclerotic disease and type 2 diabetes or impaired glucose tolerance.
Researchers conducted a phase 2, double blind, randomized, placebo-controlled trial using MRI to evaluate the effects of canakinumab (Novartis) treatment, compared with placebo, on arterial function and structure. In total 189 patients with atherosclerotic disease and type 2 diabetes or impaired glucose tolerance at nine centers in Canada, Germany, Israel, the United Kingdom and the United States were enrolled. All patients were older than 80 years and more than 60% were men.
Patients were randomly assigned to receive subcutaneous canakinumab 150 mg (n = 95) or placebo (n = 94) monthly for 1 year. Integrated vascular MRI was performed at baseline, 3 months and 1 year.
The primary efficacy endpoints were the effect of canakinumab on aortic distensibility and total plaque burden. The primary safety endpoints were safety and tolerability of treatment.
At 1 year, the change between the canakinumab and placebo groups in mean carotid artery wall area was –3.37 mm2 (P = .06), proximal ascending aorta wall area was –19.07 mm2 (P = .13), proximal descending aorta wall area was –4.36 mm2 (P = .66), distal descending aorta wall area was –6.36 mm2 (P = .46), ascending aorta distensibility was 0.03 x 103 mm Hg-1 (P = .87), proximal descending aorta distensibility was 0.06 x 103 mm Hg-1 (P = .78) and distal descending aorta distensibility was 0.06 x 103 mm Hg-1 (P = .82), according to the findings.
“We found no statistically significant treatment effect of 12 months’ treatment with canakinumab on magnetic resonance-derived measures of vascular structure or function. However, in each of the common carotid arteries individually, and in the combined vessel average, there was a suggestion of possible retarded progression of atherosclerotic burden,” Robin P. Choudhury, DM, from Oxford Acute Vascular Imaging Center, Radcliffe Department of Medicine, University of Oxford, United Kingdom, and colleagues wrote.
Compared with placebo, the canakinumab group had significant reductions in high-sensitivity C-reactive protein at 3 months (geometric mean ratio [GMR] = 0.568; 95% CI, 0.436-0.74) and 1 year (GMR = 0.56; 95% CI, 0.414-0.758).
Canakinumab treatment also reduced lipoprotein(a) levels compared with placebo at 1 year (–4.3 mg/dL; P = .025). However, the canakinumab group exhibited an increase in triglyceride levels (GMR = 1.2; 95% CI, 1.046-1.38).
Eighty-six percent of patients had type 2 diabetes and 14% had impaired glucose tolerance. In this population, treatment with canakinumab did not affect HbA1c, HOMA-IR or HOMA-, fasting blood glucose or 2-hour glucose obtained during an oral glucose tolerance test, according to the findings.
“Notwithstanding these negative results, we eagerly await the results of the ongoing event-based CANTOS trial, which is also evaluated targeted interleukin-1 inhibition with canakinumab,” Xue-Qiao Zhao, MD, from the department of cardiology at University of Washington, Seattle, and colleagues wrote in a related editorial. – by Dave Quaile
Disclosures: Choudhury reports receiving honoraria/consultant fees from Amgen, AstraZeneca, Boehringer Ingelheim, Isis Pharmaceuticals, GlaxoSmithKline, Merck and Roche.
Zhao reports receiving research grants from AstraZeneca and Kowa Pharmaceuticals and consultant fees from Amgen and Sanofi.
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