Disease activity, lifestyle factors may predict methotrexate response in RA patients
medwireNews: A predictive model including baseline disease activity score, smoking status, and alcohol consumption may help to identify which patients with rheumatoid arthritis (RA) are likely to have a poor response to methotrexate-based treatment, researchers report.
“As early response to treatment strongly correlates with long-term clinical outcomes, starting combination therapy with a biological DMARD in patients less likely to achieve long-term response to [methotrexate] treatment […] could optimise the clinical outcome in these difficult-to-treat patients,” say Xavier Teitsma (University Medical Center Utrecht, the Netherlands).
As reported in the Annals of the Rheumatic Diseases, Teitsma and colleagues analyzed predictors of methotrexate response using data from the U-Act-Early trial, in which DMARD-naïve patients received 20 weeks of methotrexate treatment given at increasing doses (10–30 mg/week), followed by the addition of hydroxychloroquine if remission (Disease Activity Score at 28 joints [DAS28] <2.6 with ≤4 swollen joints for ≥24 weeks) was not achieved.
In all, 52% of 108 participants had an inadequate response (IR; defined as replacement of hydroxychloroquine with tocilizumab if remission was still not achieved, withdrawal due to adverse events, or inefficacy) to this step-up treatment regimen at the 1-year follow-up.
Higher DAS28 score and current smoking significantly predicted an increased risk for IR to the step-up methotrexate regimen on multivariable analysis, with odds ratios (ORs) of 2.09 and 3.02, respectively, while drinking at least 1 unit of alcohol per week was associated with a reduced risk, at an OR of 0.35.
When the researchers combined these variables into a model and categorized baseline DAS28 scores into low (2.6 to <3.2 points), moderate (3.2 to <5.1 points), and high (≥5.1 points), patients who did not smoke, consumed alcohol, and had low baseline disease activity had the lowest likelihood of having an IR, at 7%, whereas current smokers who did not consume alcohol and had high baseline disease activity had a 90% probability of IR.
The model was then validated using data from the Rotterdam Early Arthritis Cohort, and correctly distinguished between patients with and without an IR to the step-up methotrexate regimen on 68% of occasions.
These findings “confirmed the importance of disease activity and lifestyle related factors in the prediction of IR to treat-to-target step-up [methotrexate-based treatment] in patients with newly diagnosed early RA,” write the study authors.
However, they acknowledge that “it is premature to implement this treatment algorithm in clinical practice,” as further comparative studies are needed “to determine whether and to what degree a predictive model could improve decision-making in daily practice.”
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