The excellent results achieved in those with a good initial response to therapy suggest that, in some patients, 6 months of combination treatment can be safely followed by 6 months of etanercept monotherapy.

TUESDAY, August 27, 2013 (MedPage Todaty) — Patients with rheumatoid arthritis (RA) receiving monotherapy with etanercept (Enbrel) didn't fare as well overall as those also taking methotrexate, a non-inferiority trial found.

Among 205 patients randomized to the combination or monotherapy for an additional 6 months after an initial 6 months of combination treatment, the difference in disease activity scores was 0.4, but the non-inferiority margin was 0.6, according to Janet E. Pope, MD, of the University of Western Ontario in London, Canada, and colleagues.

However, in patients who had achieved a state of low disease activity during the first 6 months, changes on disease activity scores were similar at 12 months for the combination and monotherapy groups, at 0.57 and 0.7, the researchers reported online in the Annals of the Rheumatic Diseases.

"This is the first study that demonstrates the need to achieve a specific disease state in order to effectively discontinue [methotrexate] in [methotrexate inadequate responders] on combination therapy," Pope and colleagues observed.

Combination therapy with a biologic agent such as etanercept plus methotrexate generally has been considered the preferable approach to treatment for RA since the advent of the tumor necrosis factor inhibitors and other biologics.

However, many patients are unwilling to take methotrexate, and rates of discontinuation because of adverse events have ranged from 10% to almost 40%.

Studies comparing combination therapy with monotherapy have had conflicting results and were limited in design and duration.

They pointed out that questions remain, such as whether combination therapy provides longer-term relief than monotherapy and if outcomes would improve further if patients were in clinical remission before stopping or reducing their methotrexate.

The study also had limitations, such as its open-label design and a high withdrawal rate before randomization.

Nonetheless, the results suggested that patients who reach a state of low disease activity with 6 months of combination and wish to stop taking methotrexate, "[etanercept] monotherapy provides an effective alternative to combination therapy for the next 6 months," they concluded.

Further analyses of CAMEO data will examine 2-year responses, radiographic changes, and genetic factors relating to treatment response.