Background/Purpose: Clinical remission or low disease activity are the main goals of rheumatoid arthritis (RA) treatment and European League Against Rheumatism guidelines recommend switching treatment after 3-6 months in patients who do not achieve these targets.¹ Despite this, in Europe the majority of patients have moderate disease activity and many of them remain on methotrexate (MTX) which may lead to disease progression and functional deterioration. Several risk matrix models have been already developed but always include a patient population with mostly severe RA and never in subjects with a stable moderate disease state. The objective of this study was to identify (a combination of) factors contributing to the risk of radiographic progression (RP) among moderate RA subjects despite MTX treatment.

Methods: Subjects from the MTX arm of the TEMPO trial² with sustained moderate RA (defined as 3.2 ≤mean disease activity score in 28 joints ≤5.1 during the last 6 months of the first year) were analyzed for radiographic progression after 2 and 3 years. Univariate logistic regression was performed to identify baseline predictors of RP. Predictor variables with p<0.10 were selected for stepwise multivariate analysis. Receiver-Operating Characteristic (ROC) analysis was used to evaluate the performance of the final model to predict disease progression; the area under the ROC curve (AUC) was calculated as a measure of accuracy.

Results: During the last 6 months of the first year, 96 subjects had moderate RA, out of 187 patients that started MTX. Of these subjects, RP (change from baseline in modified Total Sharp Score [mTSS]  ≥0.5) occurred in 48 (50%) and 54 (56%) at 2 and 3 years, respectively, with a subgroup of 25 (26%) and 33 (34%) subjects who experienced a higher degree of RP (change from baseline in mTSS >3.0) at 2 and 3 years, respectively. Univariate analysis showed erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) positivity, and C-reactive protein (CRP) levels were significantly predictive of mTSS change >3.0 at both 2 and 3 years (p<0.05 for all; Table). Multivariate analysis of these variables showed ESR and RF positivity were predictive of mTSS change >3.0 after 2 and 3 years (p<0.05 for all). ROC analysis found the AUC = 0.73 for both models, indicating a fair test of prediction.

Conclusion: Subjects with sustained moderate RA despite treatment with MTX are at risk of disease progression. Both ESR and RF positivity at baseline were strongly predictive of radiographic progression in these subjects.

References

1. Smolen JS, et al. Ann Rheum Dis 2010;69:964-75.

2. van der Heijde D, et al. Arthritis Rheum 2007;56:3928-39.