Interleukin-1-beta blockade may prevent gout attacks

Last Updated: 2018-09-20

By Will Boggs MD

NEW YORK (Reuters Health) - Interleukin-1-beta blockade with canakinumab reduces gout-attack rates without affecting serum uric acid levels, according to a post hoc analysis of data from the CANTOS trial.

"The consistent reduction in risk of approximately 50% across all of the baseline serum urate levels was surprising," said Dr. Daniel H. Solomon from Brigham and Women's Hospital, in Boston.

"One typically observes greater relative risk reductions with effective interventions among patients at higher risk. We observed similar relative risk reductions at all levels of baseline serum urate, which requires further investigation," he told Reuters Health by email.

CANTOS found reduced cardiovascular events and lung cancer mortality in patients treated with canakinumab, and earlier research showed that IL-1 beta blockade shortened acute gout attacks but did not prevent them.

Dr. Solomon's team used data from CANTOS to examine whether canakinumab reduces the risk for gout attacks and whether this effect is modified by baseline serum uric acid concentrations. Their analysis included more than 10,000 patients with median follow-up of 3.7 years.

The overall incidence of gout was 0.52 attacks per 100 person-years and was significantly lower in the canakinumab group than in the placebo group (0.38 attacks vs. 0.80 attacks per 100 person-years), the team reports in the Annals of Internal Medicine, online September 18.

Canakinumab did not affect serum uric acid concentrations, but it did reduce high-sensitivity CRP levels, compared with placebo.

The reduction in gout risk was seen at all dosages of canakinumab and across all baseline serum uric acid concentrations and did not depend on having a history of gout.

"Gout has strong associations with cardiovascular disease, diabetes, and renal disease," Dr. Solomon said. "While it has never been definitively shown that managing serum urate reduces the risk of these morbid conditions, this study begins to unravel the shared mechanisms between conditions. CANTOS showed the benefits of IL-1-beta blockade for both cardiovascular disease and gout, and now we need to focus on why."

"Since most patients do well preventing gout with urate lowering therapy, IL-1-beta blockers may have a limited role for gout prevention in typical patients," he said. "But patients with refractory gout or other conditions responsive to IL-1-beta blockade, such as cardiovascular disease, may be considered candidates for using IL-1-beta blockers for gout."

Dr. Alexander So from Centre Hospitalier Universitaire Vaudois, in Lausanne, Switzerland, who recently reviewed the role of IL-1 in gout, told Reuters Health by email, "The study confirms that IL-1-beta is a crucial driver of acute gout, and canakinumab should have a place in gout management."

"Canakinumab for gout should be revisited, and maybe the FDA (U.S. Food and Drug Administration) should reassess its decision," said Dr. So, who was not involved in the study.

Canakinumab is approved in the U.S. for the treatment of cryopyrin-associated periodic syndromes (CAPS) in adults and children 4 years of age and older, but in 2011, an FDA advisory panel voted against its use for gout due to safety concerns. In Europe, it is approved for the treatment of refractory acute gouty arthritis.

In CANTOS, patients received subcutaneous injections of one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) every three months. The cost of a single 150-mg dose is around $16,700.

Novartis funded CANTOS and the new analyses, employed one of the authors and had ties to several of Dr. Solomon's coauthors.

SOURCE: https://bit.ly/2NVS7wB

Ann Intern Med 2018.