Results from the PACES trials provides further good news for Pfizer’s Celebrex (celecoxib)

DailyUpdates 10^th May: Last week European regulators affirmed the safety of Celebrex; good news for Pfizer continues with the emergence of data from the PACES trials reporting that, compared to acetaminophen, Celebrex is both preferred by patients and is of greater efficacy.

Osteoarthritis is characterized by the degeneration of the articular cartilage and is the most prevalent form of arthritis, affecting 10% of the population, equating to a patient population of over 73 million people in the seven major pharmaceutical markets.

Current pharmacotherapy of osteoarthritis is sub-optimal. Acetaminophen (paracetamol) is recommended as initial pharmacologic therapy for knee or hip osteoarthritis, however, survey and clinical trial data indicate greater efficacy for non-steroidal anti-inflammatory drugs.  Although NSAIDs do not alter the course of disease, and disease modification is currently the ‘holy grail’ in the treatment of osteoarthritis (for an analysis of DMOARDs click here), improving the therapeutic margin of NSAIDs remains a more pressing priority in the near term.

Conventional NSAIDs are effective in treating osteoarthritis due to their ability to inhibit cyclooxygenase (COX)-1, but have a high risk of adverse gastrointestinal events. More recently developed selective COX-2-inhibitors have fewer gastrointestinal side effects and are now used in 34% of the total osteoarthritis population (for an evaluation of COX-2 R&D click here).

In 1999, the US Food and Drug Administration (FDA) approved Merck & Co’s Vioxx (rofecoxib) for the relief of the signs and symptoms of osteoarthritis, management of acute pain in adults, and the treatment of menstrual pain, or primary dysmenorrhea. It became the second COX-2, inhibitor on the market, following Searle’s launch of Celebrex (celecoxib), in the in the same year.  The COX-2 inhibitors were the biggest single innovation in the treatment of arthritis symptoms since the introduction of non-steroidal anti-inflammatory drugs (NSAIDs) and at 15 weeks post launch, total Celebrex prescriptions dispensed in the had reached $3.2 million. Celebrex is now the most widely prescribed COX-2 inhibitor in the world with over 42 million patients treated since its introduction.

Uptake of COX-2 inhibitors does however vary considerably over the seven major pharmaceutical markets with 40% of severe patients currently prescribed them in the and only 26% of severe patients receiving them in the . This variation is due to pricing and concern over side effects. Although the consensus is that COX-2 inhibitors do reduce gastrointestinal events, possible cardiovascular effects remain a concern.  Current thinking is that although the use of COX-2 inhibitors does not present a cardiovascular risk, possible cardiovascular benefits associated with non-selective COX inhibitors, primarily naproxen, may be lost.

The issue of cardiovascular safety has however recently been evaluated in detail and last week (May 3rd, 2004), Pfizer reported that European regulators had completed their safety assessment of the COX-2 class and have reaffirmed the use of Celebrex (as well as Pfizer’s other COX-2 inhibitors, Bextra and Dynastat) in a broad range of patients.

European regulators affirmed that Celebrex can be appropriately used in patients with cardiovascular disease based on the large body of data submitted by Pfizer. One of these studies, which included more than 22,000 patients, confirmed that those who received Celebrex were not at increased risk of serious coronary heart disease compared to patients who received placebo or other pain medicines (rofecoxib, naproxen and ibuprofen).

Positive news on Celebrex has now been further underlined by the recently published results of two randomized placebo-controlled cross-over clinical trials in patients with osteoarthritis of the knee or hip in which the patient preference for and efficacy of placebo, acetaminophen or  Celebrex were compared. 

In their upcoming article due to be published in the journal Annals of the Rheumatic Diseases, Pincus et all report on the PACES trials.  These trials compared the effects of treatment for 6 weeks with Celebrex 200 mg/day, acetaminophen 1,000 mg 4 times/day, or placebo.  The data demonstrate that Celebrex was more efficacious than acetaminophen while patient preferences were approximately 53% Celebrex versus approximately 26% acetaminophen. No clinically or statistically significant differences were seen in adverse events or tolerability among the 3 treatment groups. 

These data affirm that Celebrex is as well tolerated and as free of side effects as acetaminophen and, when taken in conjunction with the findings of the European regulators, suggest that fears of prescribers will be somewhat allayed.  Continuing erosion of fears over safety along with the patients’ preference for, and the improved efficacy of Celebrex compared to acetaminophen further suggest that the take up of this COX-2 will increase, and potentially that prescribing practices in and the will come closer to parity.

Source DailyUpdates 22nd April; for a full abstract of the original papers see   Ann Rheum Dis. 2004 Apr 13 [Epub ahead of print].

Recommended further reading:

• Disease Modifying Osteoarthritis Drugs - The Search for the 'Holy Grail' Continues
• Osteoarthritis - COX-2s wear down traditional NSAID use

In this edition of DailyUpdates, LeadDiscovery also highlights data from a trial comparing the efficacy and safety of rofecoxib versus nabumetone in patients with osteoarthritis of the knee...the efficacy of tacrolimus ointment compared with oral cyclosporine in adult patients affected by atopic dermatitis...novel GSK3 inhibitors...and much more.