Meta-analysis of gout flare rates after stopping preventative anti-inflammatory treatment upon initiation of urate lowering therapy

Gout is a type of arthritis that causes sudden, painful swelling in the joints—most commonly in the big toe, but it can affect other joints as well. It is caused by a buildup of uric acid in the blood, which forms crystals in the joints.

To manage gout long-term, doctors prescribe urate-lowering therapy (ULT), which can consist of medications and/or lifestyle changes which help reduce uric acid levels in the blood. However, starting ULT can sometimes trigger more gout attacks (called flares) in the first few months of treatment. To reduce this risk, people are often given additional medications—called anti-inflammatory prophylaxis—at the start of ULT. These medications can include low-dose colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), or steroids.

In 2023, a research study found that while colchicine helped prevent flares early on, stopping it after six months led to a noticeable increase in gout attacks. Interestingly, this “rebound” effect was not seen in people who had received a placebo instead of colchicine. A later review of seven studies involving nearly 3,000 people also found this rebound pattern, but it was unclear whether it was caused by colchicine alone or seen with NSAIDs too.

In our study, we will explore how common gout flares are after stopping anti-inflammatory medications during ULT. We will use individual patient data from three large gout clinical trials: the Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Gout and Cardiovascular Morbidities (CARES), the Febuxostat versus Allopurinol Controlled Trial (FACT), and the Febuxostat, Allopurinol and Placebo-Controlled Study (APEX).

We will analyze detailed information from each patient, including age, gender, ethnicity, body mass index (BMI), kidney function, past gout history, and use of urate-lowering and anti-inflammatory medications. We will track when and how often patients had gout flares, and whether they were using colchicine or NSAIDs for prevention.

We will review participant flare rates at several time points including prior to stopping anti-inflammatory flare preventative treatment, immediately following the end of anti-inflammatory preventative treatment and the final period of the trial. We will compare the percentage of people who had one or more flares during these periods and see whether flare rates were different depending on which medication was used.

To ensure our findings are reliable, we will perform extra checks based on the type of urate-lowering therapy used and how long people took the preventive medicine. We will also exclude patients who received a placebo to focus only on active treatments. We will use standard statistical methods to test whether the results are consistent across the studies.

Through this research, we hope to provide clearer answers on when and how to safely stop anti-inflammatory medications during gout treatment, helping people avoid unnecessary flares and discomfort.