Patient Factors Predictive of Colchicine-Related Adverse Events in Gout

A new observational study investigated the prognostic factors for colchicine prophylaxis-related adverse events after initiation of allopurinol, a common treatment for flare prevention after beginning urate-lowering therapy for gout.¹

People with gout were provided colchicine prophylaxis despite often being prescribed medications with the potential to interact with colchicine. Ultimately, the rate of adverse events was more frequent in those who were older, had more comorbidities, and were prescribed certain medications, while serious adverse events were rare.

“Our findings will provide much-needed information about the safety of flare prophylaxis that can inform treatment decisions when initiating allopurinol, directly benefitting people with gout and their clinicians,” wrote the investigative team, led by Ram Bajpai, PhD, school of medicine, Keele University.

A condition characterized by recurrent flares of painful joint pain and inflammation, gout has been linked with substantial comorbidity and reduced health-related quality of life.² Urate-lowering therapy (ULT) for gout can lead to the cessation of flares. Still, initiating or escalating ULT can precede a gout flare, which can lead to the stopping of the therapy by patients or practitioners.

Anti-inflammatory prophylaxis, to manage flares, commonly with colchicine, is recommended for a short period when initiating ULT.³ Patient characteristics may influence the side effects of anti-inflammatory prophylaxis. However, evidence on the factors prognostic for adverse events is often anecdotal, lacking large research studies.

Here, the investigative team sought to evaluate how co-prescriptions and other potential prognostic factors affect the risk of adverse events when initiating colchicine prophylaxis for ULT in people with gout.¹ The retrospective cohort study used the Clinical Practice Research Datalink (CPDR) databases and primary care data linked to the Hospital Episode Statistics (HES) datasets from April 1997 to the present.

Adults receiving a prescription for allopurinol and colchicine for a diagnosis of gout between April 1997 and November 2016 were included in the retrospective cohorts. All patients were followed up for 6 months or until the end of colchicine treatment, defined as 56 days after the last colchicine prescription.

Bajpai and colleagues analyzed events of interest including diarrhea, nausea or vomiting, myocardial infarction, neuropathy, myalgia, myopathy, rhabdomyolysis, and bone marrow suppression. Prescriptions for medications that could interact with colchicine treatment, including statins, in the 30 days before the index date were considered as potential interactors.

The analysis considered factors that could be associated with the rate of adverse outcomes, including age in quartiles, sex, Charlson comorbidity index, body mass index (BMI), chronic kidney disease (CKD) category, and the potentially interacting prescriptions.

During the study period, 13,945 people with gout initiated allopurinol with colchicine prophylaxis. Patients had a mean age of 63.9 years and more than two-thirds (78.2%) of the population were male. Approximately one-quarter (0.26; 95% CI, 0.25 - 0.27) of participants were prescribed ≥1 potentially adverse prescription, with statins being the most common prescription (0.21; 95% CI, 0.20 - 0.22).

Overall, there was no significantly increased risk of any adverse outcomes with the prescription of statins or digoxin. However, diarrhea, nausea, and vomiting were generally higher with older age and in female patients. The rates of myocardial infarction were higher at older ages.

After adjustment for age and sex, Bajpai and colleagues found significant associations between patient-related prognostic factors and adverse outcomes in the Charlson comorbidity index 2-4 for diarrhea and the Charlson comorbidity index ≥4 and CKD stage 4-5 for myocardial infarction.

“Reassuringly, the rate of serious adverse events was low, providing reassurance for people with gout and for clinicians,” they wrote. “We also found no evidence that the prescription of statins significantly increased the risk of adverse events except atorvastatin being associated with myocardial infarction.”

References

1. _{Bajpai R, Partington R, Muller S, et al. Prognostic factors for colchicine prophylaxis-related adverse events when initiating allopurinol for gout: retrospective cohort study. Rheumatology (Oxford). Published online April 18, 2024. doi:10.1093/rheumatology/keae229}
2. _{Chandratre P, Mallen C, Richardson J, Muller S, Hider S, Rome K et al. Healthrelated quality of life in gout in primary care: baseline findings from a cohort study. Semin Arthritis Rheum 2018;48: 61–69}
3. _{FitzGerald, JD, Dalbeth N, Mikuls T, Brignardello-Petersen R, Guyatt G, Abeles AM et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Rheumatol 2020;72:879–95.}