The safety benefit of Pfizer's COX-2 inhibitor Celebrex compared to non-selective nonsteroidal anti-inflammatory drugs is affirmed in a draft report from the Agency for Healthcare Research & Quality on osteoarthritis treatments.

Systematic reviews and meta-analyses of short-term trials and other unpublished data "would appear to suggest an overall net benefit for celecoxib compared with non-selective NSAIDs," AHRQ states in the draft document entitled "Comparative Effectiveness and Safety of Analgesics for Osteoarthritis."

The draft report's circumscribed conclusion regarding Celebrex accompanies its main finding that NSAIDs used in the treatment of osteoarthritis have unique safety profiles but no single product offers clear overall superiority in terms of safety or efficacy.

"Evidence regarding the benefits of oral NSAIDs from primarily short-term randomized controlled trials is abundant and demonstrates no clear, consistent differences for relieving pain or other osteoarthritis-related symptoms, or for superior tolerability," the draft states.

"On the other hand, much of the uncertainty and confusion regarding NSAIDs centers on their comparative safety," AHRQ says.

The draft report, which is based on research conducted by the Oregon Evidence-based Practice Center, reviewed publicly available literature on osteoarthritis treatments. After filtering out lower-quality studies, 320 publications were included for the review.

The authors also suggested that Celebrex has a safety advantage compared to Merck's withdrawn COX-2 inhibitor Vioxx (rofecoxib).

"Our re-analysis and additional modeling of results from three studies reporting myocardial infarctions, heart failure hospitalizations and gastrointestinal bleeding in the same elderly Canadian population suggests that celecoxib may confer net advantages in terms of the number of these events compared with rofecoxib and non-selective NSAIDs," the draft says.

The draft report qualified this statement, however, by stating that "additional studies on original data are needed to confirm this finding in other settings."

On the other hand, the Vioxx VIGOR trial was the first clear demonstration of the trade-off between reduced gastrointestinal risk and increased cardiovascular harms, the report says.

In discussing the possible reasons why the VIGOR trial was able to show a significantly reduced rate of ulcer complications while the Celebrex trials could not, the report states that "it is possible that rofecoxib, which has greater COX-2 selectivity, is truly more gastroprotective than celecoxib."

Merck elected to voluntarily withdraw Vioxx after results from the APPROVe trial demonstrated an increase in cardiovascular risk after 18 months (¹ Also see "Merck After Vioxx: No Merger, But No Big Near-Term Launches" - Pink Sheet, 4 October, 2004., p. 3).

The AHRQ draft report's suggestions for future research states that any new COX-2 inhibitor would necessitate larger and longer studies than those previously required for approval.

"Large, long-term trials with active and placebo-controlled arms would be needed to assess the safety and benefits of any new COX-2 selective analgesic," the report states.

FDA has supported a similar approach. The agency requested that GlaxoSmithKline perform a one- to two-year cardiovascular safety study of its pipeline COX-2 inhibitor (² Also see "GSK’s COX-2 Plans: Complete Cardio Safety Study, Test Efficacy Of Low Doses" - Pink Sheet, 2 May, 2005., p. 7).

AHRQ also identified the possible use of genetic biomarkers as a promising area of future research.

"Genetic testing could theoretically help predict patients who are at higher risk of cardiovascular complications from selective COX-2 inhibitors because of differences in the COX-2 gene promoter or other genes," the draft report states.

A study in the journal Gastroenterology found that genetic biomarkers could be used to assess which patients would have higher cardiovascular risk with the use of coxibs (³ Also see "COX-2s Patient Response Variability Could Lead To Diagnostic Tests" - Pink Sheet, 9 January, 2006., p. 11).

AHRQ's comparative effectiveness study received its funding authorization through the Medicare Modernization Act.

The deadline for peer review and comments is March 3. This is the second of several reports to be released by AHRQ. The agency published a final report on the comparative effectiveness of gastroesophageal reflux disease treatments in December (⁴ Also see "PPIs Get AHRQ Stamp Of Approval Vs. Surgery; Generics Could Be Big Winners" - Pink Sheet, 19 December, 2005., p. 17).

Celebrex Shows “Overall Net Benefit” Versus NSAIDs, AHRQ Draft Report Says

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