Methotrexate intolerance common in patients with rheumatoid, psoriatic arthritis

Gastrointestinal symptoms are common in patients who are prescribed methotrexate for rheumatoid and psoriatic arthritis, in some cases even before they start taking the drug, according to a new study.

Researchers performed a cross-sectional descriptive study of patients with both types of arthritis who were treated at 4 hospitals in the Netherlands as outpatients between May 2011 and June 2012. All patients received methotrexate for at least 3 months, along with folic acid. Data were collected on disease activity, methotrexate dose, route of administration, other medications, and history of peptic ulcers and smoking.

Patients' gastrointestinal and behavioral symptoms were assessed by asking them to complete the Methotrexate Intolerance Severity Score (MISS), which evaluates adverse effects after taking methotrexate, before taking methotrexate (anticipatory symptoms), and while thinking of methotrexate (associative symptoms). Gastrointestinal symptoms included abdominal pain, nausea and vomiting; behavioral symptoms included restlessness, irritability and refusal to take the drug. A score of 0 (no symptoms), 1 (mild symptoms), 2 (moderate symptoms) or 3 (severe symptoms) was possible for each item, and methotrexate intolerance was defined as a score of 6 or higher including 1 or more anticipatory, associative or behavioral symptom. Results were published online Dec. 18 by Arthritis Research & Therapy.

A total of 291 patients were included in the study, 249 with rheumatoid arthritis and 42 with psoriatic arthritis. Most patients (62.2%) were women; the mean age was 59.4 years. Oral administration of methotrexate was the most common route (66.7%), and the median dose per week was 20 mg. Overall, 123 patients (43%) had at least 1 gastrointestinal symptom during methotrexate treatment, most commonly nausea (32.0%), followed by abdominal pain (11.3%) and vomiting (6.5%). Before treatment, 8.6% of patients had anticipatory nausea; 11.0% had associative nausea. A total of 16.5% of patients reported behavioral symptoms, most commonly restlessness (13.1%).

Methotrexate intolerance occurred in 32 patients (11.0%), with a median MISS score of 9, all of whom had nausea after treatment. Anticipatory and associative nausea were also common in this group (56.3% and 53.1%, respectively), as were behavioral symptoms (81.3%). Of those who had behavioral symptoms, 37.5% declined methotrexate. Prevalence of methotrexate intolerance was significantly higher in patients receiving the drug via the parenteral route compared with those taking an oral formulation (20.6% vs. 6.2%; P<0.001). Intolerance was less common in patients 65 years and older than in younger patients (odds ratio, 0.21; P=0.03).

The authors noted that the MISS was designed for assessing juvenile idiopathic arthritis and needs to be validated in adults with rheumatic disease. They also pointed out that their study did not identify variables that are associated with development of methotrexate intolerance or how frequently the drug is withdrawn or another drug is substituted as a result. However, they concluded that gastrointestinal and behavioral symptoms are common in patients taking methotrexate and can also occur before treatment and while thinking about treatment in some cases.

“As persisting [methotrexate] intolerance could have a negative impact on patients' quality of life and hamper the use of [methotrexate], [rheumatoid arthritis] and [psoriatic arthritis] patients on [methotrexate] should be monitored with the MISS for early detection of [methotrexate] intolerance,” the authors wrote. “This would create a window of opportunity to intervene … and avoid incompliance and discontinuation of an otherwise efficacious treatment.