The incidence of adverse events was more common in gout patients who received allopurinol in combination with flare prevention, according to a study published in . Records of rheumatic diseases.1 However, critical events were rare and provided reassurance to clinicians and patients in the shared decision-making process.
“Long-term management of gout involves taking uric acid-lowering therapy (ULT), most commonly allopurinol, to lower serum uric acid levels. crystals gradually dissolve, stopping flare-ups,” wrote lead researcher Dr. Edward Roddy, professor of rheumatology and honorary consultant rheumatologist at Keele University in Kiel, UK, and colleagues. “Although the purpose of ULT is to prevent flare-ups, starting ULT or increasing the dose often causes a gout flare, and discontinuing ULT is discouraged because patients and healthcare professionals may think that ULT has made their gout worse. It may be possible to connect.”
Therefore, guidelines recommend concomitant use of prophylactic medications for several months during initiation of ULT to prevent and reduce gout flare-ups. Colchicine, in particular, is the recommended first-line drug throughout the initiation period.2
Researchers used linked hospital episode statistics and two matched retrospective cohort studies in the UK Clinical Practice Research Datalink (CPRD) dataset to investigate the effects of non-steroidal anti-inflammatory drugs when initiating allopurinol treatment ( We assessed the risk of adverse events associated with NSAIDs) or colchicine prophylaxis. Adult patients with gout who started allopurinol with either NSAID or colchicine prophylaxis were compared with patients who started allopurinol without prophylaxis. Patients were individually matched by gender, age, and propensity to receive appropriate prophylaxis. The association between prophylaxis and specific adverse events was assessed using a weighted Cox proportional hazards model.
A total of 13,945 patients in the colchicine cohort were matched to 13,945 patients who did not receive prophylaxis, and 25,980 patients in the NSAID cohort were matched to 25,980 who did not receive prophylaxis.
The incidence of adverse events, excluding nausea, was less than 200/10,000 patient-years (208.1; 95% confidence interval) [CI] 165.4-261.7) and diarrhea (784.4; 95% CI 694.0-886.5) in the colchicine group, and angina (466.6; 95% CI 417.2-521.8) in the NSAID group.
Adverse events such as diarrhea were more common in patients receiving colchicine than in patients not receiving prophylaxis (hazard ratio) [HR] 2.22; 95% CI 1.83 to 2.69), neuropathy (4.75; 95% CI 1.20 to 18.76), myelosuppression (3.29; 95% CI 1.43 to 7.58), myalgia (2.64; 95% CI 1.45 to 4.81), and Myocardial infarction (MI) (1.55; 95% CI 1.10, 2.17). However, nausea and vomiting were comparable (1.34; 95% CI .97 to 1.85).
Patients receiving NSAID prophylaxis were more likely to have angina pectoris (1.60; 95% CI 1.37 to 1.86), myocardial infarction (1.89; 95% CI 1.44 to 2.48), acute kidney injury (1.56; 95% CI 1.20 to 2.03), and were more likely to experience digestive disorders. Patients with ulcer disease (1.67; 95% CI 1.14 to 2.44) were compared with patients without ulcer disease.
The researchers pointed to the study’s large sample size and data tied to hospital records over 20 years as strengths of the study. However, gout was diagnosed by clinical diagnosis rather than classification criteria. Additionally, only adverse events severe enough to require consultation or hospitalization were included in the study. Therefore, milder events may have been missed. The observational nature of the study created the possibility of misclassification, and the researchers were unable to draw causal inferences.
“Which patients are at highest risk of adverse events from prophylaxis and the cardiovascular effects of colchicine as reported in randomized controlled trials in people at high risk of cardiovascular events due to a history of coronary heart disease?” Future studies are needed to determine whether the benefits apply to other patients as well, “people with gout,” the researchers concluded. “Our findings provide much-needed information about the safety of preventing inflammatory flare-ups and can inform treatment decisions when starting allopurinol and the choice of colchicine or NSAIDs for prophylaxis. can directly benefit gout patients and their clinicians.”
References
- Lodi E, Bajpai R, Forrester H, et al. Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: a propensity score-matched cohort study in the UK Clinical Practice Research Datalink. [published online ahead of print, 2023 Oct 3]. An Rheum This. 2023;ard-2023-224154. doi:10.1136/ard-2023-224154
- Richet P, Doherty M, Pascual E, et al. Updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76:29–42. doi:10.1136/annrheumdis-2016-209707