Along with other directly beneficial effects in patients with a history of myocardial infarction, interleukin-1beta inhibition with canakinumab appears to prevent or reduce anemia, according to an exploratory analysis of a large randomized trial. "Previous work from the CANTOS trial demonstrated that interleukin-1 inhibition can reduce rates of major cardiovascular events, lung cancer, and gout," Dr. Paul M. Ridker of Brigham and Women's Hospital in Boston told Reuters Health by email. "The current data showing a further reduction in anemia underscores the multi-system nature of disease and the many ways that chronic immune modulation can, in the future, be used for therapeutic means." Dr. Ridker and colleagues analyzed outcomes from 8,683 trial participants without anemia at enrollment and 1,303 with prevalent anemia. During a median follow-up of 3.7 years, those without baseline anemia who were randomized to canakinumab at any dosage had significantly less incident anemia than patients on placebo (hazard ratio, 0.84; P<0.001). This effect was corroborated in formal mediation analyses, the team reports in the Annals of Internal Medicine. "This absence of an apparent dose-response effect according to randomization group," say the researchers, "was similar to what was seen for some other outcomes in CANTOS (such as gout)." Over 2 years, compared with patients with baseline anemia receiving placebo, those with baseline anemia on active treatment showed a highly significant increase in hemoglobin of 11.3 g/L. Canakinumab did increase infection risk, and it was associated with mild cases of thrombocytopenia and neutropenia but with none reaching grade 3 or higher. "These hypothesis-generating data highlight the role of IL-1beta /IL-6 pathway signaling in anemia onset in a large population with chronic inflammation and motivate the design of prospective confirmatory studies to identify populations that might benefit from anti-inflammatory therapies." Commenting on the findings by email, Dr. A. Russell Localio, a statistician and co-author an accompanying editorial, told Reuters Health that as employed here mediation analysis based on randomized trials can help to explain which treatments might lead to intended outcomes. Dr. Localio, of the University of Pennsylvania, in Philadelphia, concluded, "However, careful attention to assumptions and control of confounding are essential. When properly performed, a mediation analysis can produce helpful clinical and mechanistic insights." Novartis Pharmaceuticals funded the study. Dr. Ridker and several of his coauthors report financial ties to the company. —David Douglas Source
