VIENNA, Austria - The benefits of continuous treatment with etanercept and methotrexate (MTX) persist for 3 years, according to new results from the TEMPO trial (Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes) presented in Vienna at the Annual European Congress of Rheumatology of the European League Against Rheumatism (EULAR).1
Of 682 rheumatoid arthritis (RA) patients randomly assigned to receive 25 mg of etanercept twice weekly, MTX up to 20 mg/week or a combination of both agents, patients receiving the combination of drugs achieved better responses 3 years into the study as measured by ACR20, 50, and 70, disease activity scores in 28 joints (DAS28), mean improvement in health assessment questionnaire (HAQ) assessments, and C-reactive protein (CRP) levels.
Specifically, 84.8% of patients in the combination group achieved ACR20, compared with 68.4% in the MTX alone group and 71.7% of those receiving etanercept monotherapy. Moreover, 66.7% of patients in the combination group showed an ACR50 response, compared with 43% of patients in the MTX group and 46.2% of those taking etanercept. Approximately 50% of patients taking both drugs achieved ACR70, compared with 21.5% of patients in the MTX-only arm and 24.2% of those taking etanercept alone, TEMPO showed.
Remission rates also higher
More than 40% of those patients receiving combination therapy achieved remission according to the DAS28 measure (<2.6). By contrast 20.6% of patients in the etanercept group and 18.9% in the MTX group achieved remission according to these criteria, the study showed.
Patients in the combination group were less likely to discontinue due to lack of efficacy compared with counterparts receiving either monotherapy regimen. Rates of discontinuation due to adverse events were similar across all three groups, however, and no new safety signals occurred during the 3 years of follow-up.
"These data demonstrate sustained efficacy of combination etanercept and MTX therapy through 3 years," concludes lead researcher Lars Klareskog, MD, professor and chairman in the department of rheumatology at the Karolinska Hospital in Stockholm, Sweden. "Combination therapy resulted in achieving remission in a significant number of patients."
These 3-year results "show persistence of this response," comments Ferdinand C. Breedveld, MD, professor of rheumatology at Leiden University Medical Center in Leiden, The Netherlands. "The difference obtained in the beginning is maintained at 3 years."
This finding holds in another study presented at EULAR.2 Researchers compared ACR70 response rates from TEMPO and from the Early Rheumatoid Arthritis (ERA) trial. The treatment arms in ERA included etanercept 25 mg twice weekly, etanercept 10 mg twice weekly, and oral MTX with a mean dose of 19 mg per week. In both studies, the combination of etanercept plus MTX was more effective than either monotherapy regimen in inducing a major clinical response at 1 or 2 years, the study found.
When do we consider stopping therapy?
Now that research suggests that benefits persist, there should be an effort to determine whether patients can safely discontinue therapy, Dr. Breedveld asserts. "If you believe the efficacy of TNF antagonists, that is nice, but to stay on them without a proven decision scheme about when you should stop [is not a good strategy]," he says. "We need discontinuation studies."
Indeed, an analysis of the BeSt trial presented at EULAR suggests that clinical remission induced by treatment with infliximab and MTX may be durable in the absence of drug in a significant number of patients.3 After a mean of 12.6 months of therapy, 67 patients who had achieved a DAS44 score of <e;2.4 for at least 6 months discontinued infliximab, and had their MTX dose tapered to 10 mg per week. Of these patients, only 10 were required to reinitiate infliximab due to an increase in disease activity (after a median of 2.1 months) during follow-up through the end of year 2.
References:
- Klareskog L, Van der Heijde D, Wadulta J, et al. Sustained efficacy and safety of etanercept and methotrexate, combined and alone, in RA patients: year 3 TEMPO Trial results. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract OP0009.
- Fleischmann RM, Van der Heijde D, Klareskog L, et al. Enbrel plus MTX induces a superior major clinical response in patients with RA versus MTX or Enbrel alone: persistence of the ACR70 response. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract AB0177.
- Van der Bijl AE, Goekoop-Ruiterman YP, Breedveld FC, et al. Many early RA patients with good clinical responses to infliximab can discontinue anti-TNF alpha therapy without relapse. Presented at: Annual European Congress of Rheumatology of EULAR; June 8-11, 2005; Vienna, Austria. Abstract OP0010.