Women, Alcohol Drinkers Are at Greater Risk of Methotrexate Side Effects

November 8, 2021
Kevin Kunzmann

Alopecia and nausea risk may be more easily identified in patients initiating methotrexate for rheumatoid arthritis.

Age, sex, and even alcohol consumption may define a patient’s risk for developing nausea or alopecia while receiving methotrexate for rheumatoid arthritis, according to a new study.

In new data presented at the American College of Rheumatology (ACR) 2021 Convergence this week, a team of UK investigators observed patient demographics and associated behaviors that could indicate risk of adverse effects with the common rheumatoid arthritis therapy.

Led by Ahmad Sherbini, MD, MS, of the University of Manchester, the research team sought to summarize the prevalence of nausea and alopecia over 1 year in patients initiating methotrexate for their rheumatoid arthritis. As they noted, the first-line treatment has been historically associated with significant efficacy.

“However, certain adverse events, such as nausea and alopecia, often create considerable concerns to patients starting the treatment, and could affect their quality of life,” investigators wrote. “This may result in non-adherence to methotrexate or permanent discontinuation of treatment in the early period following the start of methotrexate.”

Sherbini and colleagues used data from the Rheumatoid Arthritis Medication Study (RAMS), a multi-center, prospective cohort analysis of patients with rheumatoid arthritis initiating first-time methotrexate treatment. Their assessment included a collection of baseline patient demographic, clinical, and medical data, and adverse events were observed at 6- and 12-month follow-ups.

The team then conducted multivariable logistic regression analyses to observe associations between candidate baseline predictors and nausea or alopecia in methotrexate-treated patients.

Their cohort included 1069 patients with early-diagnosed rheumatoid arthritis; methotrexate was initiated at a mean 59.2 years in patients. Mean duration of symptom was 7.7 months. Approximately two-thirds (65.3%) of patients were women. Nausea was reported in 31.1% of treated patients, while alopecia was observed in just 7.8%.

Women were at a more than 2-fold risk of nausea than men (OR, 2.22; 95% CI, 1.59 – 3.11), and were almost 4 times as likely to report alopecia (OR, 3.93; 95% CI, 2.01 – 7.70).

Among observed lifestyle factors, alcohol consumption was linked to a 44% increased risk of methotrexate-related nausea (OR, 1.44; 95% CI, 1.04 – 1.97) and a 98% increased risk of alopecia (95% CI, 1.11 – 3.53) than in patients who did not drink alcohol. Concomitant use of disease-modifying antirheumatic drugs (DMARDs) was actually associated with reduced risk of nausea (OR, 0.72; 95% CI, 0.50 – 1.02) and alopecia (OR, 0.62; 95% CI, 0.34 – 1.16) than in patients not taking such mediation.

Patients above the average cohort age were actually slightly less likely to report nausea than younger patients (OR, 0.97; 95% CI, 0.96 – 0.99), as were former smokers versus never smokers.

The investigators concluded that a litany of demographic and clinical characteristics could be defined to interpret specific risk of methotrexate-associated adverse events in patients with rheumatoid arthritis.

“Identifying factors associated with adverse event occurrence could help alleviate patients’ concerns and improve adherence to methotrexate,” Sherbini and colleagues wrote. “Limiting alcohol consumption may influence the likelihood of developing methotrexate-related adverse events.”

The study, “Baseline Factors Associated with the Development of Nausea and Alopecia over One Year in Patients Starting Methotrexate for Rheumatoid Arthritis,” was presented at ACR 2021.


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