Older patients with chronic kidney disease (CKD) starting low-dose methotrexate rather than hydroxychloroquine have increased risks for serious adverse events, such as myelosuppression and pneumotoxic effects, a study finds.

These drugs are commonly prescribed to treat rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, atopic dermatitis or eczema, systemic sclerosis, and psoriasis.

Flory T. Muanda, MD, PhD, of Western University in London, Ontario, Canada, and colleagues compared the risk for a hospital visit involving myelosuppression, sepsis, pneumotoxic effects, or hepatotoxic effects within 90 days of a new prescription of these oral drugs (the primary composite outcome). They propensity-score matched 2309 new users of methotrexate at a dose of 5-35 mg/wk and 2309 new users of hydroxychloroquine at a dose of 200-400 mg/d. Patients were aged 66 years or older and had an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m² but were not on dialysis.

The low-dose methotrexate group had a significant 2.1-fold increased risk for the primary composite outcome compared with the hydroxychloroquine group, Dr Muanda’s team reported in JAMA Network Open. The primary composite outcome occurred in 3.55% of the methotrexate group vs 1.73% of the hydroxychloroquine group.

In secondary analyses, low-dose methotrexate was significantly associated with a 4.4- and 2.3-fold increased risk for a hospital visit specifically for myelosuppression or pneumotoxic effects, respectively.

Methotrexate users receiving a dose of 15 to 35 mg/wk had a higher risk of the primary outcome. Risks also increased at lower eGFRs. Methotrexate is primarily eliminated by the kidneys. Patients with an eGFR less than 45 mL/min/1.73 m² taking methotrexate had a significant 2.8-fold increased risk of the primary composite outcome compared with the hydroxychloroquine group.

For every 28 older adults with an eGFR less than 45mL/min/1.73 m² starting low-dose methotrexate vs hydroxychloroquine, 1 patient was hospitalized with a serious adverse event, the investigators reported.

“The study did not assess whether low-dose methotrexate had more benefits than risks,” Dr Muanda’s team pointed out. “Whether the potential benefits outweigh the risks will need to be evaluated individually.”

The authors concluded that “patients with CKD starting low-dose methotrexate should have active surveillance, including blood tests and chest radiographs performed regularly to monitor for signs of myelosuppression, infection, hepatotoxic effects, and pneumotoxic effects.”

Reference

Muanda FT, Blake PG, Weir MA, et al. Low-dose methotrexate and serious adverse events among older adults with chronic kidney disease. JAMA Netw Open. Published online November 27, 2023. doi:10.1001/jamanetworkopen.2023.45132