Colchicine & Statins: A significant interaction? Save

The use of colchicine in rheumatologic practice is frequent. Current ACR guidelines for the management of gout support anti-inflammatory prophylaxis, including colchicine, during urate lowering therapy initiation and uptitration.1 Aside from diarrhea, colchicine use is generally well tolerated, but its metabolism via the CYP3A4 cytochrome P450 enzyme pathway poses a potential risk of medication interaction. Statins are one of the most widely prescribed medication classes also metabolized by this pathway thus positing question of additive risk when colchicine and a statin are prescribed concurrently. 

In order to further understand this relationship, Meidan et al. conducted a retrospective review of a national database.2 Their study included adults with a diagnosis of gout and/or familial mediterranean fever (FMF) and excluded those with preexisting myopathy or liver disease or recent elevations in liver enzymes or creatine kinase (CK). Patients were categorized into 4 cohorts: those without statin or colchicine treatment, statin only treatment, cochicine only treatment, or combined statin and colchicine treatment. Patients were then followed using a time-varying exposure model so that patients could contribute person-time to various categories as their medication use changed. 

The primary outcome of the study was CK elevation tiered by severity above the upper limit of normal. Tiered ALT elevation and various clinical events were secondary outcomes. The authors noted that while colchicine has now been studied in large-scale cardiology clinical trials, in which many patients are on a concurrent statin, muscle and liver enzyme elevations are often not endpoints of interest. In this study, patients were propensity estimated using multivariable logistic regression of variables such as age, ethnicity, BMI, smoking status, comorbidities, and concomitant chronic medication use and then were matched in a 1:1 ratio.

Ultimately, 104,066 patients were available after exclusion, of which 31,839 were able to be propensity scored and matched across the four treatment groups. After propensity matching, baseline characteristics were balanced. 

CK Outcomes:
Compared to no treatment exposure, patients in the statin and statin & colchicine groups had elevated hazard ratios for CK elevations >3x ULN of 1.64 (1.39-1.93, 95%) and 1.74 (1.44-1.99, 95%) respectively. The hazard ratio for colchicine use alone was 1.08 (95% CI 0.89-1.31). In a sub-group analysis of those with renal disease, any treatment group showed risk for CK elevation, compared to no treatment, highest in the combination statin & colchicine group. When stratified by statin type, both statin monotherapy and combination statin & colchicine use were associated with CK elevations >3x ULN regardless of statin type. 

ALT Outcomes:
All treatment groups were associated with an increase risk of >5x ULN ALT elevations compared to no treatment, including colchicine alone HR 1.65 (1.35-2.01), statins alone HR 1.73 (1.44-2.09) and colchicine & statins HR 2.12 (1.72-2.61). 

Clinical Outcomes:
New-onset myopathy risk characterized by development of unspecified myopathy, myositis, rhabdomyolysis, or drug-induced myopathy, was not significantly increased in colchicine only use (HR 1.12, 0.99-1.28) but was higher and significant in the statin only group (HR 1.30, 1.16-1.46) and the statin & colchicine group (HR 1.50, 1.31-1.72), with a low absolute event rate. The risk of hospitalization due to liver disease was comparable in the statin only and statin and colchicine combination groups (HR 1.68 vs. 1.66). 

This study adds helpful context about the usage and risk of dual statin and colchicine therapy in rheumatologic disease. While risk of muscle and liver enzyme elevations is most elevated in the dual usage group, this risk is largely driven by statin use on its own and only incrementally increased when colchicine is added, translating to a significant but clinically questionable risk of muscle and liver disease. It is important to note that this study excluded folks who might have been highest risk – those with preexisting muscle or liver enzyme elevations or clinical muscle/liver disease and combination use in these patients likely poses a further increased risk. The authors note a possible limitation of surveillance bias: those being treated with a statin or colchicine were more likely to have CK and LFTs measured. 

The study reinforces my personal practice in patients on statins who require colchicine therapy for gout or FMF – the concurrent use of a statin does not preclude my use of colchicine, but I monitor patients clinically for the presence of new muscle symptoms and biochemically for LFT elevations. I dose-reduce or defer colchicine use in those with kidney or liver disease, depending on the degree of impairment. 

References

1.  FitzGerald, J. D., Dalbeth, N., Mikuls, T., et al. American College of Rheumatology. (2020). 2020 American College of Rheumatology Guideline for the Management of Gout. In Arthritis Care & Research (Vol. 72, Issue 6, pp. 744–760). https://doi.org/10.1002/acr.24180

2.  Meidan, R., Loutati, R., Caspi, D., Elkayam, O., Abuhasira, R., & Eviatar, T. (2026). Real‐world safety of concomitant colchicine and statin therapy. Arthritis Care & Research. https://doi.org/10.1002/acr.80172