A landmark study highlighted Sunday during a press conference at the 64th Annual American College of Rheumatology (ACR) Annual Meeting in Philadelphia showed that twice as many patients taking
leflunomide experienced significant benefit from the rheumatoid arthritis (RA)
therapy, compared to the control group. These results are of particular
importance because patients in this study were not responding to a traditional
treatment, methotrexate; yet received significant therapeutic benefit when
leflunomide, marketed under the tradename Arava(TM), was added.
"The addition of leflunomide demonstrated significant therapeutic benefit
for patients unresponsive to the standard RA therapy of methotrexate alone,"
commented Joel M. Kremer, current director of research at the Center for
Rheumatology in Albany, New York and former head of the Division of
Rheumatology at Albany Medical College. "This finding provides crucial
insight into how we as rheumatologists should be approaching the treatment of
rheumatoid arthritis, and should provide clinicians with evidence to
re-evaluate their standard treatment protocol for RA."
When introduced in 1998, leflunomide, an oral disease-modifying
antirheumatic drug (DMARD), was the first new treatment for RA in more than a
decade. It has been shown to retard structural damage and reduce signs and
symptoms in all stages and severities of RA. RA -- one of the most common
forms of arthritis -- is a potentially crippling autoimmune disease that
affects more than two million Americans, 70 percent of whom are women.
In a 24-week multicenter, randomized, placebo-controlled trial,
263 patients with active RA who were failing on methotrexate alone, were
randomized to receive 10 mg/day of leflunomide with methotrexate (n=130; mean
dose = 16.7 mg/wk) or placebo with methotrexate (n=133; mean dose =
16.2 mg/week). Dose adjustments were made based on tolerability and efficacy.
The primary efficacy endpoint was the ACR 20 response rate assessed at
24 weeks. ACR criteria for response include the following:
- 1) at least a
20 percent improvement in both tender and swollen joint count
- 2) at least
a 20 percent improvement in three of the following five criteria:
assessment of disease activity;
- investigator's assessment of disease activity;
- pain intensity;
- functional/disability measure;
- acute phase reactants.
More than twice as many patients in the leflunomide group (46 percent)
were responders compared to the control group (20 percent), demonstrating a
clear and significant therapeutic advantage for patients in the leflunomide
group. The combination therapy was well tolerated; adverse events observed
were minor and included diarrhea, nausea and dizziness.
"We are excited to present data that proves the significant benefit of
Arava when added to a traditional therapy like methotrexate," said Dr. Kremer.
"I encourage physicians to evaluate this treatment plan for their RA patients,
to provide clinically significant additional therapeutic benefit."