Valdecoxib: CLINICAL TRIALS

9 Jul
2010

CLINICAL TRIALS

Gastrointestinal Ulceration

Despite the COX-1-sparing property of the coxibs, concern remains as to whether they have the same potential to cause gastrointestinal (GI) ulcers as conventional week, randomized, placebo-controlled study, Kivitz et al. compared the risk of GI ulceration with valdecoxib 5, 10, and 20 mg four times a day (QD); BID; and placebo in approximately 1,000 patients with OA. Patients underwent an endoscopy at pre- and post-treatment to assess the presence of an ulcer. Results showed that patients taking naproxen 10% (P< 0.05) developed significantly more GI ulcers than those taking placebo (4%) or valdecoxib 5 mg or 10 mg (3°% (P< 0.05) vs. 3°% (P<0.01), respectively). Overall, valde-coxib had a safer profile with respect to GI safety and tolerability.

As in the previously mentioned study, Agrawal et al. studied the incidence of GI ulcers in both OA and RA patients comparing valdecoxib to naproxen. The study used high-dose valdecoxib (20 mg BID and 40 mg BID) and naproxen 500 mg BID for a period of 14 weeks in approximately 1,100 patients. Prior to treatment and at week 14, endoscopies were performed to assess the development of ulcers. Inclusion criteria were patients with fewer than 10 gastroduodenal erosions and no ulcers at pretreatment. Overall, at 14 weeks, the risk of developing a GI ulcer was significantly higher in the naproxen group than in the valdecoxib 20- and 40-mg groups (18% vs. 4% vs. 8%, P<0.05, respectively). The study further evaluated the difference in ulcer rates among the OA and RA groups. There was a trend toward a higher incidence of ulcers in the OA subset and naproxen treatment group (20% [OA] and 16% [RA]). Valdecoxib 40 mg BID showed a significantly higher rate of ulcer formation than the 20 mg BID in the OA group (9% vs. 3%, P<0.05), however, these rates are still significantly lower when the results are compared to naproxen therapy (20%, P<0.05).

Anti-inflammatory Effects

Several small studies evaluated the efficacy of valdecoxib in treating conditions associated with pain and inflammation. Bensen et al. compared the efficacy of varying doses of valdecoxib (10, 20, and 40 mg QD) with naproxen (500 mg BID) and placebo in patients with RA.

Efficacy was assessed using the American College of Rheumatology-rating scale (ACR20) at two, six, and 12 weeks. The ACR20 is defined as an improvement of 20% in the number of tender and swollen joints and a 20% improvement in 3 of 5 measures, including patient pain, patient function assessment, erythrocyte sedimentation rate, patient global assessment, and physician global assessment. At week 12, the largest percentage of responders fell into the valdecoxib 10- and 20-mg dosing range; however, there seemed to be no additional benefit to increasing the dose to 20 or 40 mg (49% [10 mg] vs. 48% [20 mg] vs. 46% [40 mg], P<0.001). Overall, valdecoxib was shown to be superior to placebo and naproxen in the treatment of signs and symptoms of RA.

In addition to assessing the incidence of GI ulceration, Kivitz et al. also assessed the effectiveness of valdecoxib as compared to naproxen therapy in the treatment of OA. Valdecoxib was shown to be superior to placebo and as effective as naproxen. Kivitz et al. used the Patient’s and Physician’s Global Assessment of Arthritis to evaluate the effectiveness of all treatment groups from baseline. Overall, valde-coxib 10 mg (-1.53, P<0.01) and valdecoxib 20 mg (-1.55, P<0.01) were superior to placebo with respect to patient’s global assessment. Naproxen did show an improvement from baseline (i.e., -1.41); however, these results were not statistically significant. When compared to valdecoxib 20 mg (-1.45, P<0.05) and naproxen 500 mg (-1.43, P<0.05), the valdecoxib 10-mg treatment group (-1.52, P<0.01 compared to placebo) was shown to provide the most improvement when evaluated by the physician’s global assessment.

Makarowski et al. assessed the signs and symptoms of OA of the hip with the use of valdecoxib versus naprox-en. The Patient’s and Physician’s Global Assessment of Arthritis was used at weeks two, six, and 12 in approximately 500 patients. Similar results were seen in this study as compared to the previously mentioned trials. Valdecoxib 5 and 10 mg were superior to placebo and comparable to naproxen 500 mg BID when the patient’s global assessment was mea­sured (-0.87 (placebo) vs. -1.20 (5 mg, P<0.05) vs. -1.29 (10 mg, P<0.01), vs. -1.18 (naproxen, P<0.05)). canadian cialis online

Valdecoxib has been shown to be effective in the treatment of primary dys-menorrhea in several small studies. When compared to naproxen sodium 550 mg, the onset and duration of analgesic effects of valdecoxib 20 mg were comparable. Pain relief was achieved within one hour and lasted over 24 hours with just one dose in 72% to 85% of the patients in the valdecoxib treatment group.

Although it is new to the coxib family, valdecoxib has shown promising results in limited studies when compared to placebo and naproxen in the development of ulcers as well as in pain relief. Future trials comparing the COX-2 inhibitors will be necessary to determine any significant differences among the three drugs in the treatment of OA, RA, and primary dysmenorrhea.

Until larger studies with valdecoxib are conducted, health care providers might need to theorize some of the drug interactions as well as the adverse effects based on data from well-established studies with and rofecoxib. Most recently, the Vioxx Gastrointestinal Outcomes Research (VIGOR) Study showed high-dose rofecox-ib to have a statistically significant (P<0.002) increased incidence of cardiovascular and thrombotic events as compared to naproxen. Until additional studies are performed, theoretically, caution should be taken when administering any of the COX-2 inhibitors to patients with pre-existing cardiovascular and renal con-ditions. Overall, valdecoxib is comparable in cost to the others in its class; however, further data are needed to establish the long-term safety and drug interaction profiles of valdecoxib.

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