Incorporating biologics into treatment early in the course of rheumatoid arthritis may keep symptoms at bay for years or even indefinitely, researchers found.
The addition of etanercept (Enbrel) to methotrexate for newly symptomatic patients doubled the remission rate a year later even when etanercept was discontinued (P<0.05), Claire Sheehy, M.B., of Connolly Hospital in Dublin, Ireland, and colleagues reported at the American College of Rheumatology meeting here.
Follow-up of some patients beyond the small 48-week randomized trial showed sustained remission three years after etanercept withdrawal, which Dr. Sheehy said her group hopes would continue indefinitely.
These findings supported the idea of a window of opportunity early in rheumatoid arthritis when the burden of disease is lower and the potential of remission is greater, Dr. Sheehy said.
Biologics may not be the only way to take advantage of this window, she said.
"However you can, get the inflammation down," Dr. Sheehy said. "But the biologics seem to work more quickly."
Treatment with tumor necrosis factor (TNF) inhibitors for established rheumatoid arthritis is given indefinitely because most patients have flares when the drug is stopped, she said.
But long-term use of these expensive drugs has raised concerns about infection and malignancy, although another study presented at the meeting suggested cancer fears were unfounded. (See: ACR: No Cancer Risk with TNF-Inhibitors for Rheumatoid Arthritis)
Several trials have explored early treatment with biologics, but the only two to try withdrawal after remission used infliximab (Remicade).
So, the researchers compared 48 weeks of treatment with methotrexate alone (20 mg weekly) to a regimen of methotrexate plus etanercept (50 mg per week) with discontinuation of etanercept for patients in remission at 24 weeks.
All 40 participants had a confirmed diagnosis using ACR criteria but were in the early stages of the disease with symptoms of no more than one year before entry into the study (average 6.2 months) and no prior use of disease-modifying antirheumatic drugs (DMARDs).
After the first 24 weeks, 85% of etanercept-treated patients achieved remission defined by a Disease Activity Score in 28 joints (DAS28) of 2.6 or less compared with 35% in the methotrexate-only group (P<0.05).
At 48 weeks, twice as many etanercept-treated patients were in remission overall compared with those on methotrexate alone regardless of etanercept withdrawal (60% versus 30%).
Patients who stopped etanercept at 24 weeks actually had the highest remission rate (70%) at 48 weeks.
Improvement in symptoms at 24 weeks was greater among etanercept-treated patients as well with 95% versus 65% achieving an ACR 20 response and 75% versus 25% achieving an ACR 70 response.
Patients who had discontinued etanercept maintained better response rates through 48 weeks than those who got methotrexate alone (ACR 50 60% versus 35%, ACR 70 50% versus 30%, both P<0.05).
Both a biomarker of inflammation -- C-reactive protein -- and DAS28 scores showed a more rapid improvement with etanercept that remained through 48 weeks.
Because patients who did well and stayed in remission off etanercept tended to be those who responded quickly to the drug, gradually tapering etanercept rather than simply discontinuing it may not have made a difference, Dr. Sheehy said.
Rheumatoid factor, corticosteroid dose, and anti-cyclic citrullinated peptide antibodies did not predict patient outcomes in the study, Dr. Sheehy said, though she cautioned that the small sample size might have obscured any effect.
A larger randomized trial is now needed to replicate the results, she said.
Although the study did not include a formal cost effectiveness analysis, Sheehy's group noted that their intervention strategy cost ,750 per patient to increase the likelihood of remission 30%. Primary source: American College of Rheumatology Meeting
Source reference:
Sheehy C, et al "Remission Induction With Etanercept and Methotrexate In Very Early Rheumatoid Arthritis with Sustained Remission after Etanercept Withdrawal" ACR 2008; Abstract 2042.