NEW YORK – Etanercept can help lower disease activity or even induce remission in patients with moderate rheumatoid arthritis. However, discontinuing the drug means that almost 60% of patients will experience a disease flare over the next year, beginning within a month of discontinuation, according to Dr. Michael E. Weinblatt.
These are the findings from the PRESERVE trial, presented at the 2011 annual meeting of the American College of Rheumatology. "These are exciting data. I think they demonstrate a cost-effective way to treat RA. I was surprised it did not receive more prominence at the ACR meeting," said Dr. Weinblatt, the John R. and Eileen K. Riedman Professor of Medicine at Harvard Medical School, Boston.
Dr. Michael E. Weinblatt
Funded by Pfizer, PRESERVE compared etanercept in combination with methotrexate in subjects with rheumatoid arthritis. The findings are as yet unpublished. The lead investigator was Dr. Joseph S. Smolen, who noted during an interview at the meeting that because of reimbursement and safety concerns, "there has been a growing interest in strategies involving treatment dose reduction or discontinuation once subjects achieve adequate response."
PRESERVE compared the efficacy and safety of continuing etanercept once weekly at a 50-mg dose in combination with methotrexate, reducing the etanercept dose from 50 mg to 25 mg once weekly plus methotrexate, and withdrawing etanercept and giving placebo once weekly plus methotrexate, according to Dr. Smolen, chairman of rheumatology at the University of Vienna and Hietzing Hospital, both in Vienna.
In reviewing the specifics of the trial’s design, Dr. Weinblatt noted that it was structured into two stages. In the first, subjects with moderately active RA (defined as disease activity scores in 28 joints [DAS28] between 3.2 and 5.1) were treated with etanercept at a dose of 50 mg once weekly plus methotrexate. At 36 weeks, those who achieved either low disease activity (defined as DAS28 less than or equal to 3.2) or remission (defined as DAS28 less than 2.6) were entered into the double-blind second stage. In this phase, 604 subjects were randomized to either continuing treatment (etanercept 50 mg once weekly plus methotrexate, n = 202), treatment with a reduced dose (etanercept 25 mg once weekly plus methotrexate, n = 202) or discontinuation (placebo plus methotrexate, n = 200) for 52 weeks. A total of 497 subjects completed the second stage, said Dr. Weinblatt, who was not an investigator with the PRESERVE trial.
Dr. Josef S. Smolen
Significantly more patients in the etanercept groups maintained low disease activity than in the placebo group (continuation group: 83%, reduction group 79% vs. placebo 43%, both P less than .0001 vs. placebo). Similar findings were found for disease remission, which was achieved by 67% in the continuation group and 60% in the reduced-dose group but only 29% of the placebo group (P less than .0001 for either etanercept group vs. placebo). Etanercept-treated patients also had higher scores on other efficacy end points such as the Simplified Disease Activity Index (SDAI) low disease activity, SDAI remission, the ACR 20/50/70 responses, and the Health Assessment Questionnaire (HAQ).
No significant differences in safety were seen among the groups. Serious adverse events were noted by 6% (n = 35). During the second period, there were two deaths (0.3%) in the etanercept 50-mg group due to pulmonary embolism and septicemia.
Plotting the data according to time, by about 30 days RA had flared in 30% of subjects in the placebo group and by 90 days 50% no longer were considered to have low disease activity or to be in remission. Over the 52 weeks, the percentage of patients in the placebo group whose RA was still under control gradually declined, until only 20% had low disease activity or remission. In contrast, etanercept at both doses remained effective for 90% at 30 days and for 80% at 90 days. After about 150 days, there was almost no change in the proportion of patients still benefiting from etanercept.
Dr. Weinblatt disclosed having financial relationships with a number of pharmaceutical companies. Dr. Smolen disclosed having a relevant financial relationship with Pfizer Inc.