Frailty Predicts Risk for Methotrexate Discontinuation in Rheumatoid Arthritis

Methotrexate use must be carefully monitored in patients with RA with frailty.

In patients with rheumatoid arthritis (RA), frailty is a significant contributor to discontinuation of methotrexate (MTX) treatment, according to study results published in Clinical Rheumatology.

Patients with RA with frailty are at increased risk for adverse events (AEs) that may lead to treatment discontinuation.

A study was designed to evaluate whether frailty status was associated with MTX discontinuation risk among patients with RA.

Patients with RA receiving methotrexate who visited 1 of 3 hospitals in Japan between June and August 2020 were followed up through 2022 to assess for MTX discontinuation due to AEs.

Frailty was evaluated using the Kihon Checklist (KCL), in which “frailty” was defined as a score of 8 points or greater; “prefrailty” as a score of 4 to 7 points; and “normal” as a score of 0 to 3 points.

Patients (N=323) had a mean age of 64.8 (SD, 13.7) years; 77.7% were women. Participants were diagnosed with RA an average of 11.6 years previously, were receiving 8.0 mg of MTX, had a KCL score of 6.1 points, and 33.8% had frailty.

Our findings highlight the importance of evaluating frailty in RA patients.

Overall, 24 patients (7.4%) discontinued MTX during a mean follow-up of 20.9 months. Patients who discontinued vs did not discontinue treatment had higher rates of diabetes mellitus (29.2% vs 5.7%; P =.001), interstitial pneumonia (20.8% vs 5.7%; P =.016), hypertension (37.5% vs 16.4%; P =.022), used other conventional synthetic disease-modifying antirheumatic drugs (DMARDs) more frequently (58.3% vs 36.8%; P =.049), had higher KCL scores (mean, 9.0 vs 5.9 points; P <.001), and had frailty more commonly (58.3% vs 31.8%; P =.012).

Risk for MTX discontinuation associated with diabetes mellitus (adjusted hazard ratio [aHR], 4.16; 95% CI, 1.68-10.28; P =.002) and frailty (aHR, 2.34; 95% CI, 1.02-5.37; P =.046).

Best predictors for methotrexate discontinuation included the activities of daily living (aHR, 1.43; 95% CI, 1.12-1.84; P =.005) and physical strength (aHR, 1.41; 95% CI, 1.08-1.83; P =.011).

The study may have been limited by lack of data on the duration of MTX use at baseline.

Researchers found, in addition to diabetes status, frailty status was an important predictor for methotrexate discontinuation due to AEs among patients with RA, which led them to conclude, “Frailty (KCL) may serve as a comprehensive index with a high predictive power for MTX discontinuation due to AEs. Our findings highlight the importance of evaluating frailty in patients [with RA].”