Wednesday, January 26, 2005

STUDIES REPORT MIXED RESULTS ABOUT COX-2 INHIBITOR EFFECTS

Three studies published in the Jan. 24 issue of the Archives of Internal Medicine show mixed results on the effects of COX-2 inhibitors, including Merck & Co. Inc.'s Vioxx (rofecoxib) and Pfizer Inc.'s Celebrex (celecoxib).

In one of the studies, 404 patients with osteoarthritis, type 2 diabetes and hypertension were randomized to receive Celebrex 200 mg/day, Vioxx 25 mg/d or naproxen 500 mg twice daily for 12 weeks.

Researchers found that reductions in pain, mobility and stiffness were similar in all treatment groups, but that Vioxx significantly increased the average 24-hour systolic blood pressure reading after six weeks of treatment.

"While further study is warranted, these results suggest the need for careful monitoring and control of BP when NSAIDs or COX-2 inhibitors are chosen for osteoarthritis management in patients with hypertension and type 2 diabetes and further suggest need for careful evaluation of currently available as well as future COX-2-specific inhibitors and nonspecific NSAIDs in this population," the authors wrote.

Another one of the studies involved 6,250 patients, predominately black females, who were enrolled in Maryland's Medicaid program and were considered at high risk for having a cardiovascular event.

Researchers analyzed medical and prescription claims for enrollees who received at least a 60-day supply of a COX-2 inhibitor or other prescription nonsteroidal anti-inflammatory pharmaceutical brand (NSAID) between June 2000 and July 2002, and who had not used these drugs in the previous six months. Naproxen users were not included.

Overall, 12 percent of the patients had at least one cardiovascular thrombotic event within one year of treatment, but researchers found no difference in the rate of incidence between the COX-2 inhibitor group and the NSAID group.

The third study involved 98,821 elderly patients in Canada who had been taking warfarin, a blood thinner, between 2000 and 2001. During the study, 361 of the patients were admitted to the hospital for upper gastrointestinal (GI) hemorrhage. Among these patients, researchers found that those who were also taking a nonselective NSAID, Celebrex or Vioxx were more likely to experience upper GI bleeding.

The authors of this study wrote "Given the observational nature of this study, our findings should be viewed as preliminary and require confirmation through well-designed clinical trials. Regardless, physicians and pharmacists who care for elderly patients taking warfarin should be aware of the potential risks of concomitant therapy with NSAIDs or COX-2 inhibitors, particularly because the latter are among the fastest-growing class of prescription medications and have rapidly gained acceptance in clinical practice."

In a separate early-release article posted on The Lancet's Web site, Dr. David Graham, from the Food and Drug Administration, and colleagues said that, based on a study using data from Kaiser Permanente in California, Vioxx may have caused up to 140,000 cases of serious heart disease in the United States.

Researchers of this study based their estimate on 1.4 million patients, aged 18 to 84 years, who were treated with an NSAID between Jan. 1, 1999, and Dec. 31, 2001. They found that Vioxx users had a 34 percent higher chance of developing coronary heart disease than other NSAID users.

Monday, January 24, 2005

IN BRIEF: PFIZER INC.

Pfizer Inc. has agreed to delay the release of its COX-2 inhibitor Onsenal (celecoxib) in the European Union until a European Medicines Agency committee completes its assessment of COX-2 inhibitors and cardiovascular safety. The committee has requested further clarifications and analyses of data from Pfizer for two trials involving Onsenal. The drug, which The Wall Street Journal said was originally planned for an early 2005 launch, received European approval in 2003 to treat adenomatous intestinal polyps in familial adenomatous polyposis. It has the same active ingredient as Pfizer's COX-2 inhibitor Celebrex, but an agency spokesman told Reuters that Onsenal would have been prescribed at a much higher dose.

Wednesday, December 22, 2004

PRELIMINARY DATA LINK NAPROXEN TO INCREASED RISK OF CARDIOVASCULAR EVENTS, FDA SAYS

The Food and Drug Administration issued a statement late Monday stating that preliminary results of a study being conducted by the National Institutes of Health demonstrated an increased risk of cardiovascular events among patients taking naproxen.

The painkiller is available over-the-counter as Bayer AG's pharmaceutical brand name Aleve and by prescription under various names, such as Roche Laboratories Inc.'s Naprosyn.

The NIH study was assessing whether naproxen and Pfizer Inc.'s Celebrex (celecoxib) have a preventive effect on the development of Alzheimer's disease. The trial included 2,500 patients who were given either naproxen, Celebrex or placebo. After a follow-up of approximately three years, the subjects taking naproxen had a 50 percent increased risk of cardiovascular events; patients taking Celebrex demonstrated no such increased risk in this particular study.

The NIH halted the clinical trial but will continue to monitor the patients.

The FDA statement urges patients who are taking OTC naproxen "to carefully follow the instructions on the label." The FDA also stated that the recommended dose of 220 mg twice daily should not be exceeded, and that the drug should not be used for more than 10 days unless otherwise directed by a physician.

"This illustrates the fundamental dynamic that all drugs have risks," said Dr. Steven Galson, acting director of the FDA's center for drug evaluation and research, The New York Times reported. "All should be taken carefully."

As reported previously, Celebrex also has been linked to an increased risk of cardiovascular events in one study.

However, the Times article suggested that the recent news about naproxen could prove beneficial to Pfizer, which, during the past several days, has been urging the public and health officials to place the possible Celebrex heart risk in the proper context, since similar drugs may be just as harmful to the heart and that other Celebrex studies so far have not shown an increased risk of cardiovascular events.

Tuesday, December 21, 2004

PFIZER TO SUSPEND CELEBREX DTC ADVERTISING

Pfizer Inc. said it will suspend its direct-to-consumer advertising of Celebrex (celecoxib) in light of last week's news that the painkiller has been linked in one study to an increased risk of cardiovascular events and after discussions with the Food and Drug Administration.

The move covers radio, newspaper and magazine advertising, although the company plans to continue marketing Celebrex to physicians, The Associated Press reported.

The FDA called the commitment open-ended, according to The Wall Street Journal. The agency also asked Pfizer to temper the tone of its marketing to physicians to ensure that they are aware of the new findings as well as the FDA's recommendations about the drug's use.

Specifically, while the agency recognized the preliminary nature of the new information about the potential cardiovascular problems associated with higher doses of Celebrex, it nonetheless recommended that physicians evaluate alternative therapies for their patients currently using Celebrex.

"At this time, if physicians determine that continued use is appropriate for individual patients, FDA advises the use of the lowest effective dose of Celebrex," the regulatory body said in a statement.

The FDA is in the process of obtaining all available data from other ongoing Celebrex trials and will determine the appropriate regulatory action as soon as possible, it added.

During the first nine months of this year, Pfizer spent more than $70 million advertising Celebrex to U.S. consumers, according to AP.

Pfizer shares closed at $24.29, down $1.46, or 5.7 percent, in heavy trading on the New York Stock Exchange.

Friday, December 17, 2004

STUDY SHOWS INCREASED CARDIOVASCULAR RISK WITH CELEBREX USE, PFIZER REPORTS

Pfizer Inc. announced it received new information Thursday night that revealed patients taking Celebrex (celecoxib) in one of two long-term cancer trials demonstrated an increased cardiovascular risk over those taking placebo, but no increased risk was found in the second trial.

An independent safety review board reported this preliminary information to Pfizer based on additional reviews and analyses conducted by a panel of cardiovascular experts. The two studies, which are designed to follow patients for five years, have enrolled a total of nearly 3,600 patients.

During the Adenoma Prevention with Celecoxib (APC) study, patients who were treated with 400 mg and 800 mg of Celebrex daily showed an approximately 2.5-fold increase in the risk of experiencing a major fatal or non-fatal cardiovascular event as compared with patients who received placebo. The National Cancer Institute, which sponsored the trial, has suspended Celebrex dosing in the study due to this statistically significant result.

However, in the Prevention of Spontaneous Adenomatopus Polyps (PreSAP) study, subjects who received 400 mg of Celebrex daily rather than placebo have shown no increased cardiovascular risk.

"In placing this new information in context, it is important to understand that the APC trial results differ from both the PreSAP cardiovascular results as well as the large body of data that we and others have accumulated over time, in which an increased risk of serious cardiovascular events in arthritis patients, even at higher-than-recommended doses, had not been seen," said Dr. Joseph Feczko, president of Pfizer worldwide development.

In September and October, the Data Safety and Monitoring Boards of both trials conducted a preliminary review of the available data and allowed the studies to proceed. They also convened a panel of cardiovascular experts to further evaluate the data, leading to these "new" and "unexpected" results, said Pfizer Chief Executive Officer Hank McKinnell.

Another long-term trial is currently studying Celebrex in patients at high-risk for Alzheimer's disease. Approximately 750 of the 2,000 subjects are receiving 400 mg of Celebrex per day. A Dec. 10 review of adverse events conducted by a safety board did not result in any recommendations to make any changes in the study.

McKinnell said the company is working to fully understand the results and to quickly communicate any new information. It also plans to continue working with the FDA regarding the company's plan to sponsor a major study for further assessing Celebrex in patients with osteoarthritis and who are at high risk for cardiovascular disease.

Celebrex, a COX-2 inhibitor, is currently approved in the United States for relieving the signs and symptoms of osteoarthritis (at recommended daily doses of 100 mg to 200 mg) and rheumatoid arthritis (at recommended daily doses of 200 mg and 400 mg). At daily does of up to 800 mg, it is approved as an adjunct to usual care for reducing the number of adenomatous colorectal polyps from the rare familial adenomatous polyposis condition.

Pfizer shares were at $25.01, down $3.97, or 13.7 percent, in heavy midday Wall Street trading.

Wednesday, December 8, 2004

VIOXX PATIENTS MORE LIKELY TO HAVE NONFATAL MYOCARDIAL INFARCTION THAN CELEBREX PATIENTS, NEW STUDY SHOWS

Patients using Merck & Co. Inc.'s pharmaceutical brand Vioxx (rofecoxib) have a higher rate of myocardial infarction than patients using Pfizer Inc.'s Celebrex (celecoxib), according to a new study.

The case-control study included 1,718 patients with a first-time, non-fatal MI and 6,800 control subjects from 36 hospitals between May 1998 and December 2002. All patients were between 40 to 75 years of age.

There was no association between COX-2 inhibitor use and nonfatal MI. However, Celebrex users showed statistically significantly lower odds of nonfatal MI than Vioxx users. Celebrex patients were 57 percent less likely to have a nonfatal MI than control patients while Vioxx patients were 16 percent more likely to have a nonfatal MI than control patients.

Comparing Vioxx to Celebrex directly, Vioxx was 2.7 times more likely to result in a nonfatal MI than Celebrex. Vioxx was 3.4 times more likely to result in a nonfatal MI compared with naproxen. Celebrex was 23 percent less likely to result in a nonfatal MI compared with ibuprofen or diclofenac.

"Cardiovascular effects among the COX-2 inhibitors seem different, but further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors and potential differences among them," the study authors concluded.

The study findings appear on the Annals of Internal Medicine Web site and will be published in the Feb. 5 print edition.

Thursday, October 21, 2004

PFIZER REPORTS INCREASED THIRD-QUARTER INCOME, REVENUE

Pfizer Inc. Wednesday reported third-quarter earnings that slightly exceeded Wall Street expectations and revenue that fell slightly short of expectations.

The firm's net income, including special items, totaled $3.34 billion, or $0.44 per diluted share, up approximately 50 percent from $2.24 billion, or $0.29 per share, in the same period of last year. Excluding non-recurring items, Pfizer earned $4.16 billion, or $0.55 per share, compared with $3.68 billion, or $0.48 per share, last year. Analysts surveyed by Thomson First Call had anticipated earnings of $0.54 per share this year, excluding special items, CBS MarketWatch reported.

Overall revenue in the quarter reached $12.83 billion, up 4 percent from $12.35 billion in the year-ago quarter. The company had been expected to generate approximately $13.23 billion in revenue, according to Thomson First Call. The firm's human pharmaceutical operations generated $11.29 billion in revenue, representing a 3 percent improvement from last year.

The company's top-selling products in the quarter included the statin Lipitor (atorvastatin), with $2.74 billion (up 11 percent year-over-year); calcium-channel blocker Norvasc (amlodipine besylate), with $1.04 billion (down 6 percent); anxiety drug Zoloft (sertraline) and epilepsy drug Neurontin (gabapentin), with $802 million (down 3 percent) and $764 million (up 10 percent), respectively; COX-2 inhibitor Celebrex (celecoxib), with $797 million (up 14 percent); antibiotic Zithromax (azithromycin), with $339 million (down 4 percent); erectile dysfunction drug Viagra (sildenafil citrate), with $403 million (down 15 percent); and allergy drug Zyrtec (cetirizine), with $333 million (down 4 percent).

Pfizer shares closed at $28.30, down $0.70, or 2.4 percent, in moderate trading on Wall Street.

Tuesday, October 19, 2004

TRIAL OF CELEBREX IN PATIENTS WITH RECENT HEART ATTACK, HISTORY OF OSTEOARTHRITIS PLANNED FOR 2005

Pfizer Inc. will sponsor a study to assess the effects of Celebrex (celecoxib) on inflammation and cardiovascular events among patients with osteoarthritis and among patients at high-risk for cardiovascular disease, according to a company press release.

Following the recent recall of Merck & Co. Inc.'s Vioxx (rofecoxib), the cardiovascular safety of COX-2 inhibitors, such as Celebrex, has come under scrutiny. Part of the problem is that most past trials of COX-2 inhibitors have omitted patients at high-risk for cardiovascular disease, the Wall Street Journal reported.

Pfizer's trial is expected to begin in early 2005 and will involve more than 4,000 patients who have had a recent heart attack and have a history of osteoarthritis.

Although Vioxx and Celebrex are in the same class of drugs, they may function differently. Drugs in a class "do some things the same and some things differently. . . . It is perfectly reasonable to expect that one may have different actions than the other," Dr. Jeffrey Borer, professor of cardiovascular medicine at Cornell University, told the Journal.

"Small mechanistic studies suggest that Celebrex's anti-inflammatory properties, as well as additional unique Celebrex-specific characteristics, may improve vascular function in patients with established coronary artery disease," said Dr. Joseph Feczko, Pfizer's president of worldwide development.

The randomized, placebo-controlled study will be conducted for a two-year period.

Tuesday, October 19, 2004

TRIAL OF CELEBREX IN PATIENTS WITH RECENT HEART ATTACK, HISTORY OF OSTEOARTHRITIS PLANNED FOR 2005

Pfizer Inc. will sponsor a study to assess the effects of Celebrex (celecoxib) on inflammation and cardiovascular events among patients with osteoarthritis and among patients at high-risk for cardiovascular disease, according to a company press release.

Following the recent recall of Merck & Co. Inc.'s Vioxx (rofecoxib), the cardiovascular safety of COX-2 inhibitors, such as Celebrex, has come under scrutiny. Part of the problem is that most past trials of COX-2 inhibitors have omitted patients at high-risk for cardiovascular disease, the Wall Street Journal reported.

Pfizer's trial is expected to begin in early 2005 and will involve more than 4,000 patients who have had a recent heart attack and have a history of osteoarthritis.

Although Vioxx and Celebrex are in the same class of drugs, they may function differently. Drugs in a class "do some things the same and some things differently. . . . It is perfectly reasonable to expect that one may have different actions than the other," Dr. Jeffrey Borer, professor of cardiovascular medicine at Cornell University, told the Journal.

"Small mechanistic studies suggest that Celebrex's anti-inflammatory properties, as well as additional unique Celebrex-specific characteristics, may improve vascular function in patients with established coronary artery disease," said Dr. Joseph Feczko, Pfizer's president of worldwide development.

The randomized, placebo-controlled study will be conducted for a two-year period.

Thursday, August 26, 2004

RESULTS FROM FDA-SPONSORED STUDY INDICATE PATIENTS RECEIVING VIOXX 25 MG/DAY HAVE THREE-FOLD INCREASED RISK OF AMI, SUDDEN CARDIAC DEATH COMPARED WITH REMOTE NSAID USE

New data from a trial sponsored by the Food and Drug Administration indicate patients administered Vioxx (rofecoxib) 25 mg or more per day have a risk of experiencing an acute myocardial infarction (AMI) or sudden cardiac death that is more than three times that of remote non-steroidal anti-inflammatory drug users.

Researchers analyzed data from a subset of Kaiser Permanente patients, aged 18 to 84 years, who were treated with a COX-2-selective or non-selective NSAID between Jan. 1, 1999, and Dec. 31, 2001. Patients were enrolled in the study beginning with their first prescription and followed until the end of the study period, disenrollment, AMI or death.

In the trial, approximately 1.4 million patients contributed 2.3 million person-years of observation time. The study population included 40,405 patients administered Celebrex and 26,748 Vioxx recipients. Overall, there were 8,199 acute cardiac events, including 6,675 AMI cases and 1,524 cases of sudden cardiac death observed during the trial.

Results showed that treatment with Vioxx 25 mg/day or more conferred a 3.15-fold greater risk of AMI or sudden cardiac death compared with "remote use of any NSAID." Such a risk was also observed with lower doses of Vioxx (less than 25 mg/d), but did not achieve statistical significance.

Even at lower doses, the risk of AMI or sudden cardiac death was increased among patients treated with Vioxx compared to patients treated with Pfizer Inc.'s Celebrex (celecoxib).

"Based upon the evidence in this study, I do not think doctors should prescribe high-dosage Vioxx and patients should not take it," said study investigator Dr. David Graham of the office of drug safety at the FDA.

However, Mary Elizabeth Blake, spokeswoman for Merck, said the company "disagrees with the conclusion" of the trial, according to The Wall Street Journal. She noted past randomized trials comparing Vioxx with placebo that showed no significant difference in the incidence of serious cardiac events in Vioxx-treated patients.

She added such randomized trials are "more authoritative" than the current trial and similar studies that draw conclusions based on observations of a population after treatment with a variety of therapies, according to The Wall Street Journal.

These data were presented in Bordeaux, France, at the annual meeting of The International Society for Pharmacoepidemiology. Although the FDA funded the trial under contract with Kaiser Permanente, the researchers' materials do not necessarily reflect the views of the FDA, according to a Society press release.

Friday, August 20, 2004

NSAID-ASSOCIATED GASTROPATHY HAS DECLINED MARKEDLY DURING PAST DECADE

The risk of serious nonsteroidal anti-inflammatory drug (NSAID)-associated gastropathy decreased 67 percent in patients with rheumatoid arthritis between 1992 and 2000, researchers reported in the August edition of Arthritis & Rheumatism.

The finding is based on a study of 5,598 patients with RA representing 31,262 patient-years of observation between 1981 and 2000. The primary outcomes were the number and incidence of serious gastrointestinal events that required hospitalization; secondary endpoints included the percentages of patients receiving NSAIDs and gastroprotective agents, patient risk factors and other variables.

The rate of GI-related hospitalization increased from 0.6 percent per year in 1981 to a peak of 1.5 percent in 1992, and then decreased to 0.5 percent in 2000, indicating a 67 percent decrease between 1992 and 2000. Trends in the rate of GI-related hospitalization during the periods of rise (1981-1992) and decline (1993-2000) were statistically significant.

GI-related hospitalizations as a percentage of all hospitalizations decreased from 7.3 percent in 1981 to 5.7 percent in 1992 and 4.8 percent in 2000. Among those patients who were exposed to NSAIDs, the percentage of GI-related hospitalizations was 0.5 percent in 1981, 2.1 percent in 1992, and 0.5 percent in 2000.

The average age of the study patients increased from 56.7 years in 1981 to 62.1 years in 1992 and remained relatively constant thereafter. The percentage of patients receiving NSAIDs decreased from 87 percent in 1981 to 76 percent in 1992 and remained relatively constant thereafter.

The mean Health Assessment Questionnaire disability index score increased from 1.17 in 1981 to 1.31 in 1992, and then declined to 1.07 in 2000. Average pain scores and patient global health assessment scores similarly rose and then decreased.

Dosages of ibuprofen and non-cardiac aspirin decreased approximately 40 percent between 1993 and 2000, while dosages of other NSAIDs did not change appreciably. The proportion of patients taking low-dose aspirin increased from 3 percent in 1992 to 8 percent in 2000.

The proportion of patients receiving NSAIDs considered "less toxic," such as ibuprofen, Pfizer Inc.'s Celebrex (celecoxib) and Merck & Co. Inc.'s Vioxx (rofecoxib), increased from 19 percent in 1993 to 48 percent in 2000. The proportion of patients receiving NSAIDs considered "more toxic," such as aspirin, naproxen and diclofenac, decreased from 52 percent in 1993 to 42 percent in 2000.

The use of H2 receptor antagonists increased rapidly from 1981 to 1992 and the use of proton-pump inhibitors increased from none in 1992 to 16 percent in 2000.

"As long as trends continue toward the use of safer NSAIDs, more frequent use of proton-pump inhibitors and de-escalation of dosages, particularly in high-risk patients, the trend toward reduction in the incidence of NSAID gastropathy is likely to continue," the researchers said.

Thursday, July 1, 2004

VIOXX, BUT NOT CELEBREX, ASSOCIATED WITH INCREASED RISK OF NEW-ONSET HYPERTENSION AMONG ELDERLY PATIENTS DURING RECENT TRIAL

In a group of senior patients, use of Merck & Co. Inc.'s Vioxx (rofecoxib) was associated with an increased risk of new-onset hypertension compared with use of Pfizer Inc.'s Celebrex (celecoxib), a non-specific nonsteroidal anti-inflammatory drug (NSAID) or no NSAID, according to data published June 28 on the Web site of the journal Hypertension.

Researchers studied 17,844 patients aged 65 years or older who received prescription drugs through the Pennsylvania Pharmaceutical Assistance Contract for the Elderly or the New Jersey Pharmaceutical Assistance Program for the Aged and Disabled between 1998 and 2000. During the study period from 1999 to 2000, 3,915 of these patients began treatment for hypertension. For each patient with hypertension, four control patients who had not yet become cases were selected from the eligible patients.

Multivariable logistic models were used to assess the relative risk of new-onset hypertension that required treatment among patients using the COX-2-specific inhibitors--Vioxx or Celebrex--as compared with those taking a non-specific NSAID or no NSAID.

Patients treated with Vioxx demonstrated a significant increased risk (60 percent) of new-onset hypertension relative to patients who received Celebrex or no NSAID. Similarly, use of Vioxx was associated with a significant increase (40 percent) in the relative risk compared with patients treated with a non-specific NSAID. Celebrex was not linked to an increased risk in these models.

There was no evident dose relationship or duration relationship between either COX-2-specific inhibitor and new-onset hypertension.

Additionally, patients with a history of chronic renal disease, liver disease or congestive heart failure showed a two-fold higher relative risk of new-onset hypertension if they received Vioxx rather than Celebrex.

"Although this study cannot prove causality, it adds significant new information about the risk of hypertension requiring treatment for patients taking [Vioxx] seen in typical practice," the investigators concluded.

Monday, June 21, 2004

ASPIRIN MAY RESULT IN MORE QALYS, LESS COST THAN COX-2 INHIBITORS IN COLORECTAL CANCER CHEMOPREVENTION, NEW FINDINGS REVEAL

According to new model estimates, healthy men using aspirin for colorectal carcinoma chemoprevention may gain more quality-adjusted life years (QALY) and pay less as compared with those using COX-2 inhibitors.

The Markov decision model was structured to simulate a hypothetical cohort of healthy men aged 50 years who took either 325 mg of aspirin daily or Pfizer Inc.'s Celebrex (celecoxib) 400 mg twice daily. Researchers measured QALYs, costs, relative complications and death monthly during 10 years of follow-up. Aspirin and Celebrex were assumed to be equally effective in treating cancer.

In the base-case analysis, aspirin resulted in 0.03 more QALYs (or 11 quality-adjusted days) and cost $23,222 less per patient than COX-2 inhibitors during the 10-year period. Furthermore, the COX-2 group had 3.877 percent more complications and 0.17 percent more deaths compared with the aspirin group.

In a number-needed-to-treat format, the findings showed that for every 26 healthy men taking COX-2 inhibitors, one individual would have an excess complication during the 10 years. In addition, one individual would die from a complication-related death for every 588 patients taking COX-2 therapy.

"The results of our model suggest that aspirin is the clear choice if a healthy individual is choosing between the aspirin and [COX-2 inhibitors] for chemoprevention, assuming equal efficacy in cancer prevention," the study authors wrote. "Additional studies determining both aspirin and [COX-2 inhibitors] efficacy in preventing tumors need to confirm the equivalency assumption made for this analysis."

The study was published online ahead of print on the Web site of Cancer.

Tuesday, June 1, 2004

SENIOR PATIENTS RECEIVING VIOXX RATHER THAN CELEBREX HAVE 80 PERCENT HIGHER RISK OF HOSPITAL ADMISSION FOR HEART FAILURE

New data indicate that elderly patients taking Merck & Co. Inc.'s Vioxx (rofecoxib) or non-selective, non-steroidal anti-inflammatory drugs, but not Pfizer Inc.'s Celebrex (celecoxib), have a greater risk of hospital admission for congestive heart failure within one year of therapy initiation.

Investigators conducted a population-based, retrospective cohort study by linking administrative health care databases that included medical information on more than 1.3 million patients from Ontario, Canada, who were aged 65 years or older. Overall, they identified 11,606 new non-selective NSAID users, 18,908 Celebrex users, 14,583 Vioxx users and 100,000 non-NSAID users.

The investigators said there were 654 hospital admissions for congestive heart failure during 55,000 person-years of follow-up.

Pairwise comparisons showed that relative to Celebrex-treated patients, Vioxx users had an 80 percent increased risk of admission for congestive heart failure and non-selective NSAID users had a 40 percent higher risk.

Furthermore, the Vioxx-treated patients had a 50 percent increased risk of admission compared with non-selective NSAID users.

Among the patients with no admission during the previous three years, only those who received Vioxx showed an increased risk--80 percent--of subsequent admission relative to non-NSAID users.

These results were published in the May 29 issue of The Lancet.

However, Merck cautioned that the results had scientific drawbacks, The Wall Street Journal reported.

Merck spokeswoman Mary Elizabeth Blake said, "Because of the inherent limitations, it precludes being able to establish cause and effect." She added that Merck is currently evaluating cardiovascular risk with Vioxx in three prospective studies.

These results were published in the May 29 issue of The Lancet.

Monday, June 23, 2003

EFFICACY OF COX-2 INHIBITORS PREXIGE, CELEBREX SIMILAR IN NEW STUDY

Novartis AG's COX-2 inhibitor Prexige (lumiracoxib) was as effective as Pfizer Inc.'s Celebrex (celecoxib) in reducing osteoarthritis pain intensity and improving functional status, new data reveal.

The Phase III study, which was presented in Lisbon, Portugal at the European League Against Rheumatism annual meeting, included 1,600 patients with primary knee OA.

A total of 462 patients received 200 mg Prexige, 463 patients received 400 mg Prexige, 444 patients were administered 200 mg Celebrex and 231 patients were given placebo. The treatments were given once daily for 13 weeks.

Prexige was significantly more effective in reducing OA pain according to a visual analogue scale and improving functional status as compared with placebo.

The 200-mg dose of Prexige was as effective as Celebrex in terms of improved overall pain intensity and functional status.

At weeks two and four, the 400-mg dose of Prexige demonstrated significantly superior efficacy in terms of OA pain intensity. At weeks eight and 13, the 400-mg dose of Prexige demonstrated similar efficacy as compared with Celebrex.

The overall incidence of adverse events was similar among all four groups.

According to Reuters, if successful, Prexige will be the fifth entrant into the COX-2 inhibitor market.

Wednesday, May 21, 2003

COX-2 INHIBITORS NOT AS COST-EFFECTIVE AS GENERIC PAIN KILLERS FOR ARTHRITIS TREATMENT, STUDY SHOWS

The use of COX-2 inhibitors to treat chronic arthritis is not as cost-effective as treatment with non-selective non-steroidal anti-inflammatory drugs, according to a recent study.

Researchers determined that the new anti-inflammatory drugs, designed to reduce the risk of deadly side effects while controlling pain in arthritis patients, were "vastly" more expensive than the NSAID naproxen, according to Reuters.

In the study, cost-effectiveness of COX-2 inhibitors was measured in quality-adjusted life-years for a hypothetical group of 60-year-old patients with moderate to severe arthritis who were not taking aspirin and required long-term NSAID treatment.

Patients who entered the hypothetical lifetime treatment were administered either a 500 mg dose of naproxen twice daily, a 200 mg dose of Pfizer Inc.'s Celebrex (celecoxib) once daily or a 25 mg dose of Merck & Co. Inc.'s Vioxx (rofecoxib) twice daily.

Results showed that using a COX-2 inhibitor instead of naproxen cost $275,809 more per year to gain one additional quality-adjusted life-year.

Furthermore, COX-2 inhibitors were found to be cost-effective only when the price-per-tablet was reduced by 90 percent of the current average wholesale price.

Researchers said the risk reduction for complications by COX-2 inhibitor treatment is unlikely to "offset their increased cost versus non-selective NSAIDs in the management of average-risk patients with chronic arthritis."

They did note that the drugs may provide an acceptable incremental cost-effectiveness ratio in the subgroup of patients with a history of bleeding ulcers.

The study can be found in the May 20 edition of Annals of Internal Medicine.