Canakinumab shown to reduce rates of gout in atherosclerosis by more than half
The results of a study presented today at the Annual European Congress of Rheumatology (EULAR 2018) demonstrate that canakinumab significantly reduced the rate of gout by more than half compared to placebo, regardless of baseline serum urate level.
"These are significant results as they add to the evidence base demonstrating a potential preventative role for canakinumab in patients with gout," said Professor Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. "They will also contribute to our understanding of the interaction between gout, uric acid and cardiovascular disease."
Gout is a very common condition. It is caused by deposits of crystals of a substance called uric acid (also known as urate) in the joints, which leads to inflammation. Periods of time when gout symptoms occur are called flares. Flares can be unpredictable and debilitating, developing over a few hours and causing severe pain in the joints.
Canakinumab is a monoclonal antibody that blocks an inflammatory pathway mediated by interleukin-1β. It is licenced for the treatment of several rare auto-inflammatory disorders although it can also be used to treat flares in certain patients with gout who have contraindications to standard therapies.2 There have been some reports to date of efficacy in preventing flares, however canakinumab is currently not approved for this indication.
"Our results demonstrate a striking effect of canakinumab on reducing the risk of gout attacks in atherosclerosis patients," said Daniel Solomon, Professor of Medicine, Harvard Medical School and Brigham and Women's Hospital. "Moreover, these data illustrate serum urate as a risk marker for both gout and cardiovascular events, though canakinumab has no effect on serum urate levels due to its mechanism of action."
This report is a secondary analysis of the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) trial which studied the impact of canakinumab in the secondary prevention of cardiovascular (CV) events.3 For this analysis, all participants were divided into three groups based on their serum urate level at baseline; low (<6.9mg/dl), medium (6.9-8.9mg/dl), and high (?9.0 mg/dL). Canakinumab (pooled doses) significantly reduced the rate of flares of gout by more than half compared to placebo, across all baseline serum urate groups. The hazard ratio (95% confidence interval) was 0.40 (0.22-0.73), 0.48 (0.31-0.74), and 0.45 (0.28-0.72) for the low, medium and high baseline serum urate groups respectively. The serum urate levels were not affected by canakinumab over time, although it did reduce high sensitivity C-reactive protein (hsCRP).
By studying the rates of flares of gout and major CV events between the baseline serum urate groups, investigators demonstrated a correlation confirming it as a risk marker for both these conditions. Rates per 100-person years for the low, medium, and high baseline serum urate groups were 0.28, 1.36, and 5.94 respectively for gout-flares, and 4.1, 5.3, 5.6 respectively for major adverse CV events.
The study included 10,061 patients with stable atherosclerosis (prior heart attack) and a hsCRP 2mg/L which indicates an increased risk of CV disease. Patients were randomly assigned to receive placebo or one of three doses of canakinumab (50mg, 150mg, or 300mg) once every three months. The groups were well balanced with respect to their baseline characteristics with a median follow-up time of 3.7 years. Median age was 61 years, 74% were male, median BMI was 29.8kg/m2, median serum urate level at baseline was 6.1 mg/dl.
Serum urate and hsCRP were tested at baseline and every three months for the first year and then annually. A physician diagnosed history of gout was ascertained at baseline and subsequent attacks were assessed during follow-up as part of the systematic adverse event reporting. The rates of gout attacks and major adverse CV events (heart attack, stroke, re-vascularisation, and CV death) were compared across different baseline serum urate levels and by randomised treatment assignment.
In the results from the original trial, neutropenia was more common among patients who were assigned to receive canakinumab than among those in the placebo group, and significantly more deaths were attributed to infection or sepsis in the pooled canakinumab groups than in the placebo group (incidence rate 0.31 vs. 0.18 events per 100 person-years; P=0.02). Thrombocytopenia was more common among patients who were assigned to receive canakinumab than among those in the placebo group, but no significant difference in the incidence of haemorrhage was observed.