Prescription of colchicine and NSAIDs for acute gout flares in severe chronic kidney disease and colchicine in major drug–drug interactions: evidence from an electronic health-record based gout register

 

Nils Bürgisser 1,2, Denis Mongin 1,5, Laurie Guebey 3, Delphine Courvoisier 1,4,5, Kim Lauper 1,5,6

 

Affiliation(s):

1. Division Of Rheumatology, Department Of Medicine, Geneva University Hospitals, Geneva, Switzerland.
2. Division Of General Internal Medicine, Department Of Medicine, Geneva University Hospitals, Geneva, Switzerland.
3. Division Of Clinical Pharmacology, Geneva University Hospitals, Geneva, Switzerland.
4. Division Of Quality Of Care, Geneva University Hospitals, Geneva, Switzerland
5. Faculty Of Medicine, University Of Geneva, Geneva, Switzerland
6. Geneva Center For Inflammation Research, Department Of Medicine, Faculty Of Medicine, University Of Geneva, Geneva, Switzerland

 

 

Background: Gout predominantly affects older patients with multiple comorbidities and polypharmacy. Management of acute gout flares may be limited by contraindications related to comorbid conditions, particularly severe chronic kidney disease (CKD) and clinically significant drug–drug interactions. The 2016 EULAR recommendations advise against the use of colchicine and non-steroidal anti-inflammatory drugs (NSAIDs) in patients with severe CKD, as well as against colchicine use in combination with strong cytochrome P450 (CYP) 3A4 or P-glycoprotein (P-gp) inhibitors, due to the risk of drug accumulation and serious toxicity.1

Objectives: To assess the prescription of colchicine and NSAIDs for acute gout flares in patients with severe CKD, and the prescription of colchicine in patients concomitantly receiving strong CYP3A4 or P-gp inhibitors.

Methods: We conducted a retrospective analysis using data from an electronic health record-based gout register.2 Severe CKD was defined as an estimated glomerular filtration rate ≤ 30 ml/min/1.73 m² documented on at least two occasions over a 90-day period. Prescription of NSAIDs or colchicine for acute gout flares, defined in a previous study,3 was evaluated in this population. Clinically relevant CYP3A4 or P-gp inhibitors were classified as strong or moderate/weak. Strong inhibitors included atazanavir, clarithromycin, cobicistat, darunavir, fluconazole, ketoconazole, lopinavir, ritonavir, nirmatrelvir–ritonavir, voriconazole, and ciclosporin. Moderate to weak inhibitors included erythromycin, verapamil, amiodarone, diltiazem, and dronedarone. Prescription of colchicine within ± 3 days of exposure to a strong CYP3A4 or P-gp inhibitor was evaluated using proportions and Jeffreys 95% confidence intervals.

Findings: Of the 7,225 patients with gout included in the register, 1,542 had severe CKD. A total of 4,194 acute gout flares were identified among 2,920 patients, including 568 flares occurring in patients with severe CKD. Among these flares, 44 (7.7%, 95%CI 5.8 to 10.2) were treated with NSAIDs, 541 (95.7%, 95%CI 93.3 to 96.8) with colchicine, and 17 (3.0%, 95% CI 1.8 to 4.6) with both drugs. During acute gout flares, 121 patients were exposed to a strong CYP3A4 or P-gp inhibitor (4.1%, 95% CI 3.5 to 4.9) and 93 to a weak or moderate inhibitor (3.2%, 95% CI 2.6 to 3.9). Among patients treated with colchicine for an acute gout flare (n= 1,888), co-prescription within ±3 days of a strong inhibitor occurred in 43 cases (2.3%, 95% CI 1.7 to 3.0) and with a weak or moderate inhibitor in 47 cases (2.5%, 95% CI 1.9 to 3.3). Conversely, when restricting the analysis to patients exposed to any CYP3A4 or P-gp inhibitor during a flare (n = 201), colchicine was prescribed in only 5 cases (2.5% 95% CI 1.0% to 5.4%) (Figure 1).

Significance:  Colchicine was frequently prescribed for acute gout flares in patients with severe chronic kidney disease despite society guideline recommendations, although co-prescription with strong CYP3A4 or P-glycoprotein inhibitors was uncommon. These findings suggest partial adherence to recommendations and warrant further evaluation of colchicine safety in patients with severe chronic kidney disease.  

References: 

1. Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017;76(1):29-42. doi:10.1136/annrheumdis-2016-209707

2. Bürgisser N, Mongin D, Mehouachi S, et al. Development and validation of a self-updating gout register from electronic health records data. RMD Open. 2024;10(2):e004120. doi:10.1136/rmdopen-2024-004120

3. Bürgisser N, Mongin D, Buclin C, Courvoisier DS, Lauper K. ABS0991 GAPS IN CHRONIC AND ACUTE GOUT CARE: REAL-WORLD DATA FROM AN ELECTRONIC HEALTH RECORD-BASED REGISTER. Ann Rheum Dis. 2025;84:1588-1589. doi:10.1016/j.ard.2025.06.976