Background/Purpose:

Joint damage and functional disability can be reduced by intensive treatment of newly diagnosed rheumatoid arthritis (RA) patients during the “window of opportunity”. Although methotrexate (MTX) is considered the anchor disease-modifying anti-rheumatic drug (DMARD) for initial RA treatment, the majority of patients need additional treatment due to inefficacy or MTX-associated adverse events. Predictors of the need to add another treatment to MTX may identify patients who can benefit from intensive treatment. Starting combination treatment in such patients earlier can improve the likelihood of timely RA control.

Methods:

In U-ACT-EARLY, a double blind, placebo-controlled treatment strategy trial, 108 patients with newly diagnosed RA (1987 or 2010 criteria) were randomized to initiate MTX monotherapy according to treat-to-target principles. MTX was increased to 30 mg/week (or maximum tolerable dose) until remission (DAS28-ESR <2.6 with SJC < 4) was achieved. In the absence of remission at maximum MTX dose (~20 weeks), hydroxychloroquine (HCQ) 200 mg bid was added. If after 12 weeks, remission still was not reached, tocilizumab (TCZ) was added to MTX-HCQ. Baseline demographic, clinical, laboratory, and functional assessment data were evaluated; missing data were imputed using multiple imputation. Multivariate logistic regression with univariate preselection was used to identify factors predictive for patients requiring additional treatment.

Results:

Patients had mean disease duration ~4 weeks and high DAS28-ESR (Table 1). Fifty-six of 108 patients (51.9%) added TCZ to MTX-HCQ due to inefficacy (n=52) or adverse events (n=4) (fig.1). Multivariate logistic regression analysis identified higher DAS28-ESR (p<.001) and smoking (p=.067) as main baseline predictors for addition of TCZ. Model discrimination was reasonable with an area under the receiver operating characteristic (ROC) curve of 0.72 (95% CI: 0.63-0.82). Table 2 shows the observed probability of adding therapy for the 2 predictor categories.

Conclusion:

The majority of very early RA patients initiating MTX monotherapy in a treat-to-target strategy required addition of TCZ to achieve remission. Patients actively smoking with higher baseline DAS28-ESR scores were more likely to require additional treatment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/predicting-the-need-for-additional-treatment-in-early-rheumatoid-arthritis-patients-treated-to-target-on-methotrexate-monotherapy/