A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early, aggressive rheumatoid arthritis
Arthritis & Rheumatism, 04/27/2012
Moreland LW et al. – There were no differences in the mean DAS28–ESR during weeks 48–102 between participants randomized to methotrexate plus etanercept or triple therapy, regardless of whether they received immediate combination treatment or step–up from methotrexate monotherapy. At 102 weeks, immediate combination treatment with either strategy was more effective than methotrexate monotherapy prior to step–up. Initial use of methotrexate monotherapy with the addition of sulfasalazine plus hydroxychloroquine – or etanercept, if necessary, after 6 months – is a reasonable therapeutic strategy for early RA. The combination of etanercept plus methotrexate resulted in a statistically significant radiographic benefit over oral triple therapy.Methods
- The TEAR study is a 2–year, randomized, double–blind trial.
- Using a 2x2 factorial design, participants were randomized to one of four treatment arms: immediate combination therapy of methotrexate plus etanercept; or oral triple therapy (methotrexate plus sulfasalazine plus hydroxychloroquine); or initial methotrexate monotherapy with a step–up to one of the combination therapies at week 24 if DAS28–ESR ≥ 3.2 (all arms included matching placebos).
- The primary outcome was an observed–group analysis of DAS28–ESR scores from weeks 48 to 102.
- At the week 24 step–up period, those receiving immediate combination therapy (etanercept plus methotrexate or triple therapy) demonstrated greater reduction in DAS28–ESR compared to those on initial methotrexate monotherapy (DAS28–ESR: 3.6 vs. 4.6, p<0.0001), with no differences between regimens of combination therapy.
- For weeks 48 through 102, participants randomized to step–up arms had a DAS28–ESR clinical response that was not different than those who received initial combination therapy, regardless of the treatment arm (3.2 vs. 3.2, p=0.75).
- There was no significant difference in DAS28–ESR between participants randomized to oral triple therapy versus combination methotrexate plus etanercept (3.1 vs. 3.2, p=0.42).
- By week 102, there was a statistically significant difference in change in radiographic measurements from baseline between methotrexate plus etanercept compared to oral triple therapy (0.64 vs. 1.69, p= 0.047).