番茄社区

ANAHEIM, Calif. -- A nasal spray combining a corticosteroid and an antihistamine was better than either drug alone for relieving allergic rhinitis in a comparison with "real-world" commercial products, a researcher said here.

Half of patients receiving the combination product -- 50 mcg of fluticasone propionate plus 137 mcg of azelastine per intranasal spray (Dymista) given twice daily -- achieved a 50% reduction in nasal symptom severity scores after 2 weeks, compared with about 38% of patients receiving commercial versions of either drug alone (P-value not reported), said Warner Carr, MD, of Allergy and Asthma Associates in Mission Viejo, Calif.

The study is important because the previously published registration trials underlying the combo drug's approval last May were required by the FDA to use formulations of the fluticasone and azelastine monotherapy comparators that differed from those actually used by ordinary patients, Carr said at the American College of Allergy, Asthma, and Immunology annual meeting.

He explained that, under FDA rules, the comparator drugs in the registration trials had to use the same delivery device and the same excipients as the combination product. The latter's sponsor, Meda Pharmaceuticals, had to produce them specially for the three phase III trials used to support the combination's marketing application.

But such formulations are not what patients use in everyday life. Consequently, to demonstrate that the combination is more effective than current single-drug products, Meda contracted with Carr and colleagues to perform a direct head-to-head trial involving branded versions of fluticasone propionate (Flonase) and azelastine (Astelin).

In a poster presentation here, Carr and colleagues reported results from all 1,006 patients treated with the fluticasone-azelastine combo spray in the "real-world" trial as well as the three registration studies, versus 153 patients taking Flonase and 153 taking Astelin.

Patients in the studies were all 12 years or older with at least a 2-year history of seasonal allergic rhinitis, positive skin-prick test results for a seasonal allergen, and total nasal symptoms scores of at least 8 on a 12-point scale.

Following a 5- to 7-day run-in period to confirm the presence of allergic rhinitis, patients began 2 weeks of treatment with the study drugs.

The report from Carr and colleagues also included results from 1,013 patients in the four studies randomized to placebo, and about 1,700 patients who had been randomized to the FDA-mandated noncommercial formulations of fluticasone and azelastine.

As it turned out, the noncommercial version of fluticasone may have been more effective than Flonase. Some 46% of patients receiving the noncommercial formulation achieved at least 50% reduction in symptom scores, compared with less than 40% in the patients receiving Flonase (P-value not reported).

On the other hand, responses to Astelin monotherapy were similar to those seen with the reformulated version of azelastine used in the registration trials.

But the bottom line, Carr said, was the combination was clearly better than monotherapy with the individual drugs, irrespective of formulation.

A separate 1-year, open-label study of the combination versus fluticasone (the reformulated version) showed that adverse event rates were similar and that no loss of effectiveness with either product was seen with extended use.

J. Allen Meadows, MD, an allergist in private practice in Montgomery, Ala., told 番茄社区 that the combination product represented a real advance in nasal allergy care. "For me it's a real breakthrough," said Meadows, who was not involved in the studies.

The main issue for allergists, Meadows said, is that they see patients who have failed treatment at the primary care level. Patients usually complain of persistent symptoms despite taking multiple drugs, which may include prescription and over-the-counter oral antihistamines, decongestants, and other agents.

With intranasal corticosteroids and antihistamines emerging as the most effective treatments, a single product that contains both types of drugs provides a big boost to patient convenience, he said, and therefore to adherence.

Meadows noted the principal downside of the fluticasone-azelastine combination was its cost, because the individual components are now available as generic products.

But, he added, generics versions "are nasty with a capital N" in terms of irritation and odor -- a further discouragement to adherence.