FRI0215 LICOFELONE, AN INHIBITOR OF COX-1, COX-2 AND 5-LOX, IS AS EFFECTIVE AS CELECOXIB AND SHOWS IMPROVED TOLERABILITY DURING 12 WEEKS OF TREATMENT IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE
K Pavelka, P Bias, A Buchner, A Lammerich, U Schulz

The objective of this study was to compare the safety and efficacy of licofelone with the selective COX-2 inhibitor, celecoxib in patients with symptomatic knee osteoarthritis (OA).

Methods: After a washout period of up to 14 days for prior NSAID use, patients were randomized to receive either licofelone 200 mg bid (n=302) or celecoxib 200 mg qd (n=306) for 12 weeks in a multicenter, double-blind trial. The change in the Western Ontario and McMaster Universities (WOMAC) pain score between baseline and 12 weeks was considered the primary endpoint. To be included in the study, a baseline WOMAC score > 220 mm was needed. Responders were defined as a having a > 30% improvement from baseline in their WOMAC score at week 12.

Results: No differences in WOMAC pain scores were found between study groups when comparisons were made at baseline and week 12; respectively, 66.8+12.2 and 32.2+21.2 in the licofelone group and 67.1+12.3 and 30.7+20.4 in the celecoxib group. 77.2% of patients receiving licofelone and 77.8% of patients receiving celecoxib were considered responders.

Although lower in the patients receiving licofelone, the overall rate of adverse events was similar for both groups, 31.9 % in patients receiving licofelone and 36.4% in patients receiving celecoxib. Worsening of peripheral edema occurred less frequently in the licofelone group (2%) compared to the celecoxib group (5.9%), p=0.011.

Conclusion: These data suggest that licofelone provides an alternative to the selective COX-2 inhibitors for the treatment of osteoarthritis. There is a trend of improved tolerability of licofelone over celecoxib.

Editorial Comment: (see comment below)

FRI0217 LICOFELONE, AN INHIBITOR OF COX-1, COX-2 AND 5-LOX, IS AS EFFECTIVE AS NAPROXEN AND SHOWS IMPROVED SAFETY DURING 12 MONTHS OF TREATMENT IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE
F Blanco, A Buchner, P. Bias, A Lammerich, U Schulz

Licofelone (LIC) is an analgesic and anti-inflammatory that competitively inhibits three enzymes: cyclo-oxygenase (COX)-1, COX-2 and 5-lipoxygenase (5-LOX). This Phase III study, expands upon a 12-week trial reported at the 2002 Eular meeting (see highlights), and compares the long-term safety and efficacy of licofelone 100 and 200 mg bid with naproxen 500 mg bid.

Methods: After a washout period of up to 14 days for prior NSAID use, patients were randomized to receive either licofelone 100 mg bid (n=235), licofelone 200 mg (n=240), or naproxen 500 mg bid (n=229) for 12 months in a multicenter, double-blind trial. The change in the Western Ontario and McMaster Universities (WOMAC) pain score from baseline to weeks 4, 26, and 52 was considered the primary endpoint. To be included in the study, a baseline WOMAC score > 50 mm greater than at screening was needed.

Results: At week 52, the mean change in WOMAC pain scores from baseline were 27.1mm, 30.2mm, and 27.7mm for 100 mg licofelone, 200 mg licofelone, and naproxen, respectively. The mean changes in WOMAC total score from baseline to week 52 were 21.0mm, 24.9mm, and 22.6mm for 100 mg licofelone, 200 mg licofelone, and naproxen, respectively. By week 4, 200 mg licofelone was significantly more effective than 100 mg licofelone (p=0.01) and remained so throughout the study. The efficacy of 200 mg licofelone and naproxen were similar throughout the study.

Adverse events were similar in all three groups, with similar frequency; 59.2%, 56.3%, and 66.7% in patients treated with 100 mg licofelone, 200 mg licofelone, and naproxen, respectively. GI adverse evernt were reported by 20.6% (L-200), 22.5% (L-100), and 24.1% (Nap) of patients. Aggravated hypertension was reported more frequently in patients treated with naproxen (3.1%) compared with licofelone (0.4% for both doses; p<0.017).

Conclusions: The 12-month data shows that licofelone has comparable efficacy to naproxen but with less GI toxicity, thereby offering the possibility of an alternative treatment for patients with OA.

Editorial Comment: There are two major pathways of arachidonic acid metabolism, the cyclooxygenase pathways that results in the synthesis of prostaglandins, and the lipoxygenase pathway that results in the formation of leukotrienes. Although leukotriene inhibitors have been successful for the treatment of asthma, they have not been efficacious in the treatment of joint inflammation. Licofelone is a new class of antiinflammatories, the LOX/COX inhibitors. These two studies appear to confirm that leukotrienes may not have much of a role in joint inflammation given that liclofelone is similar to naproxen in efficacy. Although there is a theoretical reason that a LOX/COX inhibitor might have a safer GI profile, these studies are too small to determine this fully.

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