TEMPO Trial
BeSt Trial

The TEMPO trial was designed to compare the safety and efficacy of etanercept and methotrexate (MTX) therapy alone and in combination in patients with active rheumatoid arthritis (RA), who had failed prior DMARD therapy. Additionally, the progression of structural damage was assessed. Radiographic results after one year are presented here. Results on efficacy are presented in abstract OP0003.

Methods: Patients with active RA were treated with either etanercept 25 mg twice weekly (n= 233), MTX up to 20 mg/weekly, or a combination of etanercept and MTX (n=231). The progression of structural damage was assessed by comparing changes in van der Heijde-modified total Sharp scores (TSS - defined by change in TSS of <0.5 or <3.0) and smallest detectable difference (SDD; <6.2).

Results: A total of 642 patients were analyzed. Combination therapy with etanercept and MTX was statistically more effective in inhibiting radiographic progression than either drug alone. Additionally, etanercept alone showed greater benefit than MTX alone. The table below showed the percentage of patients with no progression at one year by TSS <0.5, <3.0, or <SDD.

Conclusion: Combination therapy with etanercept and MTX inhibits structural joint damage significantly more than monotherapy with either drug alone. Etanercept monotherapy shows additional benefit over MTX monotherapy at minimizing radiographic progression.

Editorial Comments: These results are encouraging although not surprising. That the combination of etanercept and MTX is more effective than the respective monotherapies is consistent with the recent ASPIRE trial data in early RA comparing infliximab and MTX to MTX alone. The TEMPO study is unique, however, in also having a control group with TNF inhibitor monotherapy. Indeed, the combination is more effective than etanercept alone is in suppressing progression of joint damage.

(top of page)

De Vries-Bouwstr, et al presented one-year radiographic and health assessment questionnaire (HAQ) results from the BeSt trial, a multicenter, single blind, randomized study comparing multiple treatment regimens in patients with early RA. (see OP0103 for results from the BeSt trial examining patient treatment preferences)

Methods: 508 patients with RA < 2years and no prior DMARD therapy were randomized to one of four treatment groups: Group 1 (n=125): Sequential monotherapy starting with methotrexate (MTX) up to 25 mg/week, next treatment step sulphasalazinr (SSA), followed by leflunomide; Group 2 (n=122): Step-up therapy from MTX, next step add SSA, then add hydroxychloroquine; Group 3 (n=133): Step-down therapy from MTX + SSA + prednisone 60 mg tapered to 7.5 mg; and Group 4 (n=128): Treatment with MTX (7.5 mg/wk for 2 weeks, then 15 mg/wk) and infliximab (3 mg/kg at week 0, 2, and 6, then every 8 weeks, doses increased or reduced to zero depending on disease activity score (DAS44)). DAS44, health assessment questionnaires (HAQ), and Sharp/van der Heijde radiological scores (SHS) were measured. The goal of treatment adjustments (allowed at 3 month intervals) was to attain a DAS 44 <2.4.

Results: A more rapid reduction in HAQ scores was observed in Groups 3 & 4 at 3 months compared to Groups 1 & 2, but reductions were similar in all four groups by one year. Median SHS progression was significantly less in Groups 3 and 4.

In Group 1, 27% of patients did not show any radiographic progression (values for groups 2-4 were 29%, 37%, and 46%, respectively [p=0.007]). The incidence of adverse events was similar among all groups.

Conclusion: Initial treatment with combination therapy results in significantly less radiographic progress than sequential monotherapy or step-up therapy, as well a more rapid reduction in HAQ scores.

Editorial Comments: The design of this study is complicated but based on what clinicians might realistically do in clinical practice. The results affirm and extend more conventionally designed clinical trials which have also shown greater efficacy for combination therapy initiated early compared to monotherapy (e.g., ASPIRE and TEMPO).

All information contained within the Johns Hopkins Arthritis Center website is intended for educational purposes only. Physicians and other health care professionals are encouraged to consult other sources and confirm the information contained within this site. Consumers should never disregard medical advice or delay in seeking it because of something they may have read on this website.