What are the risk factors for relapse after methotrexate dose reduction?

For patients with rheumatoid arthritis (RA), a history of cardiovascular disease, gastrointestinal disease, or liver disease, as well as prior use of nonsteroidal anti-inflammatory drugs (NSAIDs) can contribute to an increased risk of relapse after methotrexate (MTX) dose reduction, as suggested in a study.

The analysis included 304 RA patients at least 20 years old who had been receiving MTX in combination with golimumab 50 mg for ≥6 months. MTX dose reduction was defined as a reduction of at least 12 mg from the total dose within 12 weeks of the maximum dose (average ≥1 mg/wk).

Relapse occurred in 16.8 percent of the 125 patients with MTX dose reduction. Relapse was defined as Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) score of ≥3.2 or sustained (≥ twice) increase of ≥0.6 from baseline.

Factors such as age, duration from diagnosis to the initiation of golimumab, baseline MTX dose, and DAS28-CRP did not significantly differ between the relapse and no-relapse groups.

In multivariable logistic regression analysis, relapse after MTX dose reduction was highly likely among patients with prior use of NSAIDs (adjusted odds ratio [aOR], 4.37, 95 percent confidence interval [CI], 1.16–16.38; p=0.03), those with a history of cardiovascular disease (CVD; aOR, 2.36), those with a history of gastrointestinal disease (aOR, 2.28), and those with a history of liver disease (aOR, 3.03).

Patients with vs without MTX reduction group were more likely to have CVD (17.6 percent vs 7.3 percent; p=0.02) and less likely to have previous exposure to biologic disease-modifying antirheumatic drugs (11.2 percent vs 24.0 percent; p=0.0076).

In light of the present data, attention should be given to RA patients with a history of CVD, gastrointestinal disease, liver disease, or prior NSAID use when considering MTX dose reduction to make sure that the benefits outweigh the risk of relapse.