Familial Adenomatous Polyposis (FAP): Celebrex was evaluated to reduce the number of adenomatous colorectal polyps. A randomized double-blind placebo- controlled study was conducted in patients with FAP. The study population included 58 patients with a prior subtotal or total colectomy and 25 patients with an intact colon. Thirteen patients had the attenuated FAP phenotype.

One area in the rectum and up to four areas in the colon were identified at baseline for specific follow-up, and polyps were counted at baseline and following six months of treatment. The mean reduction in the number of colorectal polyps was 28% for Celebrex 400 mg BID, 12% for Celebrex 100 mg BID and 5% for placebo. The reduction in polyps observed with Celebrex 400 mg BID was statistically superior to placebo at the six-month timepoint (p=0.003). (See Figure 1.)

Figure 1: Percent Change from Baseline in Number of Colorectal Polyps (FAP Patients)

Special Studies

Celecoxib Long-Term Arthritis Safety Study (CLASS)

The Celecoxib Long-Term Arthritis Safety Study (CLASS) was a prospective long-term safety outcome study conducted postmarketing in approximately 5,800 OA patients and 2,200 RA patients. Patients received Celebrex 400 mg BID (4-fold and 2-fold the recommended OA and RA doses, respectively, and the approved dose for FAP), ibuprofen 800 mg TID or diclofenac 75 mg BID (common therapeutic doses). Median exposures for Celebrex (n = 3,987) and diclofenac (n = 1,996) were 9 months while ibuprofen (n = 1,985) was 6 months. The primary endpoint of this outcome study was the incidence of complicated ulcers (gastrointestinal bleeding, perforation or obstruction). Patients were allowed to take concomitant low-dose ( ≤ 325 mg/day) aspirin (ASA) for cardiovascular prophylaxis (ASA subgroups: Celebrex, n = 882; diclofenac, n = 445; ibuprofen, n = 412). Differences in the incidence of complicated ulcers between Celebrex and the combined group of ibuprofen and diclofenac were not statistically significant.

Those patients on Celebrex and concomitant low-dose ASA (N=882) experienced 4- fold higher rates of complicated ulcers compared to those not on ASA (N=3105). The Kaplan Meier rate for complicated ulcers at 9 months was 1.12% versus 0.32% for those on low dose ASA and those not on ASA, respectively (see WARNINGS – Gastrointestinal (GI) Effects – Risk of GI Ulceration, Bleeding and Perforation).

The estimated cumulative rates at 9 months of complicated and symptomatic ulcers for patients treated with Celebrex 400 mg BID are described in Table 2. Table 2 also displays results for patients less than or greater than 65 years of age. The difference in rates between Celebrex alone and Celebrex with ASA groups may be due to the higher risk for GI events in ASA users.

Table 2: Complicated and Symptomatic Ulcer Rates in Patients Taking Celebrex 400 mg BID (Kaplan-Meier Rates at 9 months [%]) Based on Risk Factors

In a small number of patients with a history of ulcer disease, the complicated and symptomatic ulcer rates in patients taking Celebrex alone or Celebrex with ASA were, respectively, 2.56% (n=243) and 6.85% (n=91) at 48 weeks. These results are to be expected in patients with a prior history of ulcer disease (see WARNINGS – Gastrointestinal (GI) Effects – Risk of GI Ulceration, Bleeding, and Perforation and ADVERSE REACTIONS – Safety Data from CLASS Study – Hematological Events).

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