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

Ann Rheum Dis. 2023 Dec;82(12):1618-1625. doi: 10.1136/ard-2023-224154. Epub 2023 Oct 3.

Abstract

Objectives: To determine the risk of adverse events associated with colchicine or non-steroidal anti-inflammatory drug (NSAID) prophylaxis when initiating allopurinol for gout.

Methods: We conducted two matched retrospective cohort studies in linked UK Clinical Practice Research Datalink and Hospital Episode Statistics datasets. Adults initiating allopurinol for gout with (1) colchicine or (2) NSAID prophylaxis were compared with those initiating without prophylaxis, individually matched by age, sex and propensity to receive the relevant prophylaxis. Weighted Cox proportional hazards models investigated associations between colchicine/NSAID and specified adverse events.

Results: 13 945 individuals prescribed colchicine were matched to 13 945 with no prophylaxis and 25 980 prescribed NSAID to 25 980 with no prophylaxis. Adverse event incidence rates were <200/10 000 patient-years except diarrhoea (784.4; 95% CI 694.0 to 886.5) and nausea (208.1; 95% CI 165.4 to 261.7) for colchicine and angina for NSAID (466.6; 95% CI 417.2 to 521.8). Diarrhoea (HR 2.22; 95% CI 1.83 to 2.69), myocardial infarction (MI) (1.55; 95% CI 1.10, 2.17), neuropathy (4.75; 95% CI 1.20 to 18.76), myalgia (2.64; 95% CI 1.45 to 4.81), bone marrow suppression (3.29; 95% CI 1.43 to 7.58) and any adverse event (1.91, 95% CI 1.65 to 2.20) were more common with colchicine than no prophylaxis, but not nausea/vomiting (1.34; 95% CI 0.97 to 1.85). Angina (1.60; 95% CI 1.37 to 1.86), acute kidney injury (1.56; 95% CI 1.20 to 2.03), MI (1.89; 95% CI 1.44 to 2.48), peptic ulcer disease (1.67; 95% CI 1.14 to 2.44) and any adverse event (1.63; 95% CI 1.44 to 1.85) were more common with NSAID than without.

Conclusions: Adverse events were more common when allopurinol was initiated with prophylaxis, particularly diarrhoea with colchicine. Other events were uncommon, providing reassurance for patients and clinicians to enable shared decision-making.

Keywords: Anti-Inflammatory Agents, Non-Steroidal; Epidemiology; Gout.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allopurinol / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Cohort Studies
  • Colchicine / adverse effects
  • Diarrhea / chemically induced
  • Diarrhea / epidemiology
  • Diarrhea / prevention & control
  • Gout Suppressants / adverse effects
  • Gout* / drug therapy
  • Humans
  • Myocardial Infarction* / chemically induced
  • Propensity Score
  • Retrospective Studies
  • United Kingdom / epidemiology
  • Uric Acid

Substances

  • Colchicine
  • Allopurinol
  • Uric Acid
  • Gout Suppressants
  • Anti-Inflammatory Agents, Non-Steroidal