Glaxo Wellcome Advair Compliance To Be Studied Following Approval

Glaxo Wellcome plans to look for improved patient compliance with Advair Diskus compared to other asthma treatments in post-marketing studies.

FDA Pulmonary Allergy Drugs Advisory Committee consultant William Vollmer, MD, Kaiser Permanente, suggested Glaxo conduct trails on compliance during the committee's Nov. 23 review of Advair.

"I would take a look at what happens with compliance...and patient acceptance and provider acceptance," Vollmer said. Trials could examine long-term utilization patterns and enroll patients not well controlled by inhaled corticosteroids.

Patient adherence is being studied in the U.K., where the product has been available since March. "Real-time data should be available sometime next year," Glaxo Wellcome U.K. representative Rick Fuller, MD, said.

Glaxo consultant Homer Boushey, MD, University of California-San Francisco, said that Advair could improve compliance because it combines 50 mcg salmeterol with three different doses of fluticasone - 100 mcg, 250 mcg and 500 mcg - in a single device.

Advair could also reduce confusion about medications and selective discontinuation of ICS, both of which are current compliance problems, Boushey suggested.

Glaxo Wellcome Chief Medical Officer Richard Kent, MD, quoted a survey which estimated that 61% of patients with moderate persistent asthma mistakenly consider their asthma well or completely controlled, while 32% of those with severe persistent asthma mistakenly consider their asthma well controlled.

Committee guest Jean Ford, MD, Harlem Hospital Center, agreed that Advair had the potential to improve compliance, although there was no data on the subject.

Committee consultant Andrea Apter, MD, University of Pennsylvania, asked about the cost of Advair, noting that price is an important factor in compliance. Advair pricing in the U.K. is equal to or slightly less than the two components purchased separately, Fuller said.

Committee consultant Michael Niederman, MD, Winthrop University Hospital, was skeptical that Advair's cost would improve compliance in some patients. "It still may be a lot cheaper to take one than a cheaper combination....Taking fluticasone alone is going to be cheaper than taking Advair."

Advair was studied in 1,824 patients in several different clinical trials. In trial 3002, Advair 100 mcg was superior to salmeterol, fluticasone and placebo arms for both of the primary endpoints. The first primary endpoint was the number of patients discontinuing the trial because of predefined asthma symptoms. Seventy-nine Advair patients remained in the 12-week trial, compared to 70 patients on fluticasone, 57 on salmeterol and 30 on placebo.

The trial's other primary endpoint was forced expiratory volume levels measured over one second in the morning. Patients treated with Advair 100 mcg had a significantly better FEV1 than those treated with salmeterol, fluticasone or placebo.

In trial 3003, Advair 250 mcg was also superior to fluticasone, salmeterol and placebo for both of the primary endpoints. Advair 500 mcg led to a peak expiratory flow rate that was superior to fluticasone in trial 3019. Advair proved to be as efficacious as concurrent therapy with the two separate components of the drug in three other trials.

The committee voted unanimously in favor of recommending Advair for two of the populations FDA raised for consideration - patients already well-controlled on ICS and salmeterol and patients inadequately controlled on corticosteroids alone.

Seven committee members agreed that Advair should be indicated for patients inadequately controlled on short and long-acting beta agonists. Niederman and two other committee members said they would recommend Advair be indicated for patients who had not yet tried ICS monotherapy as long as they had moderate to severe persistent asthma.

Regarding the use of Advair for patients who were inadequately controlled on short-acting beta agonists alone, Committee Chair Curtis Sessler, MD, Medical College of Virginia, said "I would feel uncomfortable proposing the combination drug for mild persistent patients, but I would not feel uncomfortable with it for moderate persistent." The committee voted 9-1 against an indication for the treatment of patients inadequately controlled on short-acting beta agonists alone.