Objective: To assess whether disease activity levels at treatment initiation or during the first 3 months of therapy predict disease activity at 1 year after treatment initiation.
Methods: Pooled patient data from early rheumatoid arthritis (RA) clinical trials (n = 1,342) of methotrexate (MTX), tumor necrosis factor (TNF) inhibitor monotherapy (adalimumab and etanercept), and the combination of the two (adalimumab or infliximab plus MTX) were used for the primary analyses. Pooled data from clinical trials of MTX and of TNF inhibitor plus MTX in late RA (n = 712) were used for validation of the results. Disease activity was primarily assessed using the Simplified Disease Activity Index (SDAI); in addition, we calculated the Disease Activity Score 28-joint assessment (DAS28) and the Clinical Disease Activity Index (CDAI). Associations of disease activity measures at baseline and at 1, 2, 3, and 6 months with disease activity values or disease activity states at 1 year were performed using Spearman's rank correlation, analysis of variance, and diagnostic testing procedures, including receiver operating characteristic (ROC) curve analyses, and probit analysis.
Results: Correlations with SDAI values at end point were significant (P < 0.0001) at baseline, and increased to r = approximately 0.6 at 3 months. The area under the ROC curve indicated a high diagnostic test yield with respect to the 1-year outcome (area under the ROC curve approximately 0.8). At all time points, including baseline, the group of patients who achieved remission at 1 year had lower average SDAI values than did those whose disease activity was high at 1 year. The groups achieving low or moderate disease activities at 1 year had SDAI values lying between. Baseline disease activity was less associated with disease activity at the end point for treatment with TNF inhibitor plus MTX, indicating its effectiveness over a broader range of baseline disease activity, but the association with end point disease activity was similar to that in the MTX treatment group at 1 month after treatment initiation. The data were similar when scores on the DAS28 and CDAI were used and were fully validated in the independent cohort of patients with late RA.
Conclusion: The level of disease activity at baseline and especially during the first 3 months of treatment is significantly related to the level of disease activity at 1 year. Patients who reach a moderate or low disease activity status after 3-6 months of therapy may require switching to alternative therapies. Our findings indicate that intensive and dynamic treatment strategies that include a closer look at disease activity at 3 months in patients with early and late RA is warranted.