Multiple testing in the 'Canakinumab in atherosclerosis' trial: correction required?
| Autor: | Robin P, Choudhury, Jacqueline S, Birks, Venkatesh, Mani, Luca, Biasiolli, Matthew D, Robson, Philippe L, L'Allier, Marc-Alexandre, Gingras, Nadia, Alie, Mary Ann, McLaughlin, Craig T, Basson, Alison D, Schecter, Eric C, Svensson, Yiming, Zhang, Denise, Yates, Jean-Claude, Tardif, Zahi A, Fayad |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
Interleukin-1beta HbA1c glycosylated hemoglobin IL-1RA interleukin-1 receptor antagonist Antibodies Monoclonal Humanized C-reactive protein Double-Blind Method homeostasis model assessment HOMA homeostasis model assessment IGT impaired glucose tolerance Glucose Intolerance Humans Original Investigation Antibodies Monoclonal Arteries T2DM type 2 diabetes mellitus Middle Aged Atherosclerosis PWV pulsed wave velocity IL interleukin CI confidence interval hs-CRP high-sensitivity C-reactive protein Diabetes Mellitus Type 2 inflammation GMR geometric mean ratio Female MRI magnetic resonance imaging interleukin-1 |
| Zdroj: | Journal of the American College of Cardiology |
| ISSN: | 0392-856X |
| Popis: | Background Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression. Objectives The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging. Methods Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months. They underwent magnetic resonance imaging of the carotid arteries and aorta. Results There were no statistically significant differences between canakinumab compared with placebo in the primary efficacy and safety endpoints. There was no statistically significant change in mean carotid wall area and no effect on aortic distensibility, measured at 3 separate anatomic sites. The change in mean carotid artery wall area was –3.37 mm2 after 12 months with canakinumab versus placebo. High-sensitivity C-reactive protein was significantly reduced by canakinumab compared with placebo at 3 months (geometric mean ratio [GMR]: 0.568; 95% confidence interval [CI]: 0.436 to 0.740; p < 0.0001) and 12 months (GMR: 0.56; 95% CI: 0.414 to 0.758; p = 0.0002). Lipoprotein(a) levels were reduced by canakinumab compared with placebo (–4.30 mg/dl [range: –8.5 to –0.55 mg/dl]; p = 0.025] at 12 months), but triglyceride levels increased (GMR: 1.20; 95% CI: 1.046 to 1.380; p = 0.01). In these patients with type 2 diabetes mellitus or impaired glucose tolerance, canakinumab had no effect compared with placebo on any of the measures assessed by using a standard oral glucose tolerance test. Conclusions There were no statistically significant effects of canakinumab on measures of vascular structure or function. Canakinumab reduced markers of inflammation (high-sensitivity C-reactive protein and interleukin-6), and there were modest increases in levels of total cholesterol and triglycerides. (Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients; NCT00995930) |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|