"Lumiracoxib 400 mg Once Daily Comparable With Indomethacin 50 Mg 3 Times Daily for Treatment of Acute Gout Flares: Presented at EULAR"
By Chris Berrie
AMSTERDAM, THE NETHERLANDS -- June 30, 2006 -- The selective cyclooxygenase-2 (COX-2) inhibitor lumiracoxib shows noninferior efficacy to the nonsteroidal anti-inflammatory drug (NSAID) indomethacin in patients with acute gout as well as being well tolerated and showing fewer adverse events.
These findings were presented by principal investigator Roland Willburger, MD, head, department of orthopedic rheumatology, Orthopaedic University Clinic, Bochum, Germany, here on June 24[th at the Annual European Congress of Rheumatology (EULAR).
Gout is a common disease, especially among men older than 40 years, and it is the most common inflammatory joint disease in this population. "It is very painful, and so there is a strong need for analgesic and anti-inflammatory drugs," Dr. Willburger said.
The multicenter, randomized, double-blind, double-dummy, active-controlled, parallel-group study included ambulatory male and female patients 18 years and older who had an acute attack of gout in 4 joints or less, as diagnosed according to the 1977 American College of Rheumatology (ACR) classification criteria. Onset had to have been within 48 hours prior to evaluation.
Patients had to experience at least moderate pain intensity (3 or more on the 5-point Likert scale) in the target joint at baseline, with pain intensity assessed after the effects of any previous analgesic therapy had abated.
The main exclusion criteria were as follows: acute attack of gout before the last 48 hours prior to evaluation; rheumatoid arthritis; infectious arthritis; pseudo-gout or other acute forms of inflammatory arthritis; use of specific NSAIDs in the previous 4 weeks; and previous or active peptic ulceration or clinically significant gastrointestinal bleeding.
Subjects were randomized to either indomethacin 50 mg 3 times daily (n = 117; mean age, 56.1 years; female, 37%) or lumiracoxib 400 mg once daily (n = 118; mean age, 56.8 years; female, 37%). Paracetamol was provided as rescue medication at a minimum dose of 3 mg/day.
The primary objective was to demonstrate that this lumiracoxib regimen was noninferior to the indomethacin regimen, according to mean change from baseline of pain intensity of the study joint over days 2 to 5. This was assessed approximately 4 hours after the first daily dose of study medication on each day.
The secondary objectives were to assess the safety and tolerability profile of these medications, and to explore secondary efficacy assessments, such as patient global assessment of response to therapy.
The patient baseline characteristics were similar across both treatment groups, with acute monoarticular gout seen in 79.5% of the indomethacin group and 79.7% of the lumiracoxib group; the remaining patients in each group had acute polyarticular gout.
For the primary endpoint of noninferiority of lumiracoxib to indomethacin, in the per-protocol population this was shown as the estimated difference between treatments for the change from baseline in pain intensity over days 2 to 5 (-0.004; 95% confidence interval, -0.207, 0.199), which satisfied the prespecification that the lower limit of the confidence interval had to be > -0.5. Here, both treatment groups showed a mean reduction in pain intensity from baseline of 1.29 on the Likert scale for days 2 to 5.
Both of these regimens also showed clinically relevant improvements by the first pain assessment (4 hours postmedication; day 1). For pain reported by the patients as severe or extreme, lumiracoxib produced a reduction from baseline of 52.7% to 26.8%; indomethacin resulted in a 50.0% to 29.1% reduction. All further secondary efficacy assessments were found to be comparable between the 2 treatment regimens.
For safety and tolerability, 1.7% of patients on the lumiracoxib regimen discontinued the study drug compared with 8.5% of the indomethacin group. Similarly, while adverse events were reported in 10.2% of patients on lumiracoxib, the indomethacin group reported 22.6% adverse events. One serious adverse event of abdominal pain 2 days after discontinuation of study drug was seen in the indomethacin group, which resolved spontaneously upon hospitalization.
Dr. Willburger indicated that while the noninferiority of the lumiracoxib regimen was proven in comparison with the indomethacin regimen for efficacy in the treatment of patients with gout, lumiracoxib was well tolerated, with fewer adverse events than seen with indomethacin. Thus, lumiracoxib may provide an alternative option for the treatment of patients with acute gout, he said.
This study was sponsored by Novartis Pharma AG.
[Presentation title: Lumiracoxib 400 mg Once Daily Is Comparable to Indomethacin 50 Mg Three Times Daily for the Treatment of Acute Flares of Gout. Abstract SAT0383]
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