Allopurinol initiation generally safe among gout patients on colchicine or NSAID for prophylaxis

A recent study has delved into the potential risks of adverse events associated with the use of prophylactic medications, specifically colchicine and non-steroidal anti-inflammatory drugs (NSAIDs), when initiating allopurinol for gout treatment. The study findings highlight that initiating allopurinol with prophylactic medication is associated with an increased risk of adverse events, particularly diarrhea in the case of colchicine.

This study was published in Annals of The Rheumatic Diseases by Edward Roddy and colleagues. This investigation, consisting of two matched retrospective cohort studies, utilized data from the UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. The study compared adults initiating allopurinol for gout with and without prophylactic medication, specifically colchicine or NSAIDs. Participants were individually matched based on age, sex, and their propensity to receive the relevant prophylaxis.

Incidence Rates of Adverse Events: The majority of adverse event incidence rates were relatively low, with fewer than 200 occurrences per 10,000 patient-years, except for specific instances:

• Diarrhea: 784.4 (95% CI 694.0 to 886.5)
• Nausea: 208.1 (95% CI 165.4 to 261.7) for colchicine users
• Angina: 466.6 (95% CI 417.2 to 521.8) for those using NSAIDs.

Colchicine and Adverse Events: Users of colchicine had higher rates of adverse events, including:

• Diarrhea: HR 2.22 (95% CI 1.83 to 2.69)
• Myocardial Infarction (MI): HR 1.55 (95% CI 1.10 to 2.17)
• Neuropathy: HR 4.75 (95% CI 1.20 to 18.76)
• Myalgia: HR 2.64 (95% CI 1.45 to 4.81)
• Bone Marrow Suppression: HR 3.29 (95% CI 1.43 to 7.58)
• Any Adverse Event: HR 1.91 (95% CI 1.65 to 2.20). Nausea/vomiting, however, did not show a significant increase: HR 1.34 (95% CI 0.97 to 1.85).

NSAIDs and Adverse Events: Users of NSAIDs had higher rates of adverse events, including:

• Angina: HR 1.60 (95% CI 1.37 to 1.86)
• Acute Kidney Injury: HR 1.56 (95% CI 1.20 to 2.03)
• MI: HR 1.89 (95% CI 1.44 to 2.48)
• Peptic Ulcer Disease: HR 1.67 (95% CI 1.14 to 2.44)
• Any Adverse Event: HR 1.63 (95% CI 1.44 to 1.85).

Initiating allopurinol with prophylactic medication carries an increased risk of adverse events, particularly diarrhea in the case of colchicine, and various adverse events with NSAIDs. However, the occurrence of other adverse events remains relatively uncommon, providing reassurance for both patients and clinicians. This information enables shared decision-making and a more comprehensive understanding of the potential risks and benefits of gout treatment.

Reference:

Roddy, E., Bajpai, R., Forrester, H., Partington, R. J., Mallen, C. D., Clarson, L. E., Padmanabhan, N., Whittle, R., & Muller, S. Safety of colchicine and NSAID prophylaxis when initiating urate-lowering therapy for gout: propensity score-matched cohort studies in the UK Clinical Practice Research Datalink. Annals of the Rheumatic Diseases,2023;ard-2023-224154. https://doi.org/10.1136/ard-2023-224154