AMSTERDAM – in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.
While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks,, said at the European Congress of Rheumatology.
“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.
The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).
It’s also unclear that canakinumab () is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.
(Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study ( ). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.
In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.
Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.
SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. .