Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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4965 Citazioni (Scopus)


BACKGROUND Experimental and clinical data suggest that reducing inflammation without affecting lipidlevels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis ofatherothrombosis has remained unproved.METHODSWe conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonalantibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarctionand a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trialcompared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneouslyevery 3 months) with placebo. The primary efficacy end point was nonfatalmyocardial infarction, nonfatal stroke, or cardiovascular death.RESULTSAt 48 months, the median reduction from baseline in the high-sensitivity C-reactive proteinlevel was 26 percentage points greater in the group that received the 50-mg dose of canakinumab,37 percentage points greater in the 150-mg group, and 41 percentage points greater in the300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline.At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 eventsper 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group,3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years inthe 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mggroup, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95%CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold forstatistical significance for the primary end point and the secondary end point that additionallyincluded hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs.placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidenceof fatal infection than was placebo. There was no significant difference in all-cause mortality(hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31).CONCLUSIONSAntiinflammatory therapy targeting the interleukin-1β innate immunity pathway withcanakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrentcardiovascular events than placebo, independent of lipid-level lowering. (Funded byNovartis; CANTOS number, NCT01327846.)
Lingua originaleEnglish
pagine (da-a)1119-1131
Numero di pagine13
RivistaNew England Journal of Medicine
Stato di pubblicazionePublished - 2017

All Science Journal Classification (ASJC) codes

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