Risk of serious adverse events and death with low-dose methotrexate versus hydroxychloroquine in adults receiving dialysis

Background — Several case reports have linked low-dose methotrexate to serious adverse events, including death, in dialysis patients. We compared the risk of serious adverse events in dialysis patients initiating low-dose methotrexate versus hydroxychloroquine.

Methods — Using linked healthcare databases in Ontario, Canada (1997–2020), we identified 55 new users of low-dose methotrexate and 407 new users of hydroxychloroquine.

The primary outcome was the 90-day risk of death or hospitalization with myelosuppression, sepsis, pneumotoxicity, or hepatotoxicity. Adjusting for age, sex, and a proxy for polypharmacy, a modified Poisson regression was used to estimate adjusted risk ratios (aRR), and a binomial regression was used to estimate adjusted risk differences (aRD).

Results — The median prescribed dose was 10 mg/week (IQR, 10–17.5) for methotrexate and 300 mg/day (IQR, 200–400) for hydroxychloroquine. The primary outcome occurred in 16/55 low-dose methotrexate users (29.1%) and in 29/407 hydroxychloroquine users (7.1%); aRR: 3.14 (95% CI, 1.75 to 5.63); aRD: 19.5% (95% CI, 7.5% to 31.4%). Findings were consistent across sensitivity analyses.

Conclusion — Low-dose methotrexate should be avoided in dialysis patients whenever possible, and alternative DMARDs should be considered.