Etanercept-MTX Combo Slightly Better in RA Than Etanercept Alone

Pope JE, Haraoui B, Thorne JC, et al, The Canadian Methotrexate and Etanercept Outcome Study: a randomised trial of discontinuing versus continuing methotrexate after 6 months of etanercept and methotrexate therapy in rheumatoid arthritis. Ann Rheum Dis doi:10.1136/annrheumdis-2013-203684 [Epub Aug 26].

Rheumatoid arthritis patients taking a combination of etanercept (Enbrel) and methotrexate do better, but only slightly, than those on monotherapy with the tumor necrosis factor-α inhibitor, according to a Canadian multicenter clinical trial.

The open-label Phase IV trial is a noninferiority trial, designed to see if withdrawing methotrexate after a period of combined therapy with etanercept would be better or worse for patients than continuing both drugs-the same switch sometimes done in real-world clinical practice if patients do not tolerate methotrexate well or choose to discontinue it.

A total of 205 tumor necrosis factor inhibitor–nave rheumatoid arthritis patients with a disease activity score 28 (DAS28) of ≥3.2 and >3 swollen joints despite stable methotrexate doses received treatment with combination therapy for 6 months, then were randomly assigned to continue on 50 mg/wk of etanercept plus methotrexate (at least 15–10 mg/wk, adjusted for intolerance) or to switch to etanercept alone at the same dose for an additional 18 months.

Almost three-fourths of the patients were women, and nearly all were Caucasian. They had a mean age of 54, with a disease duration of 9 years. The DAS28 scores of the 2 groups were identical (5.4).

During the initial 6 months, mean DAS28 scores among the cohort improved from 5.4 at baseline to 3.5.

After randomization, DAS28 was stable among the etanercept/methotrexate group (n=107) and disease activity increased slightly in patients on etanercept alone (n=98).

However, stratifying the patients according to their disease activity level revealed very little difference in DAS28, regardless of therapy, at 12 months in those with low disease activity after 6 months of receiving both drugs, showing that etanercept alone was no less effective (“non-inferior”) than combination therapy for these patients. Patients who did not reach low disease activity by 6 months of combination treatment and switched to etanercept monotherapy did have a slight increase in disease activity, while those who remained on combination therapy had a continuing decrease in DAS28.
At the same time, patients with medium to high disease activity at 6 months did better on combination therapy, making this the first study to pinpoint a specific disease state in which discontinuation of methotrexate and continued use of etanercept provide an effective alternative, the researchers say.