SAN DIEGO — The use of leukotriene modifiers to treat patients with asthma was not associated with the development of Churg-Strauss syndrome in a population-based, nested, case-control study.
Shortly after leukotriene modifiers were introduced in the mid-1990s, there were reports of more cases of this rare vasculitis than would be expected, suggesting there might be a link, Dr. Leslie R. Harrold said at the annual meeting of the American College of Rheumatology.
Subsequently, an investigation of reports of the syndrome to the Adverse Event Reporting System (AERS) database, maintained by the Food and Drug Administration, found a strong association with zafirlukast and montelukast, though not with zileuton (Clin. Ther. 2004;26:1092–104).
Several possible explanations for leukotriene modifiers being related to Churg-Strauss syndrome have been suggested, such as an increased awareness of the condition, and reductions in corticosteroid doses resulting in the unmasking of an underlying eosinophilic syndrome (J. Rheumatol. 2005;32:1076–80). It also is possible that patients receiving leukotriene modifiers tend to have more severe asthma, which may predispose them to Churg-Strauss syndrome.
“To investigate this relationship, we assembled a cohort of 382,377 adults who received three or more dispensings of an asthma drug during any calendar year between Jan. 1, 1996, and Dec. 31, 2002,” said Dr. Harrold of the University of Massachusetts, Worcester. The cohort came from a national health plan and three managed care plans, with a combined patient population of 13.9 million.
Patient age, gender, drugs dispensed, diagnoses, and procedures information were obtained from automated databases, and cases of Churg-Strauss syndrome were identified through the databases and confirmed by chart reviews.
Each patient with Churg-Strauss syndrome was then matched with 100 controls for age, sex, health plan region, and year of cohort entry. Dispensing information for the patients before they were diagnosed with Churg-Strauss syndrome also was obtained.
A total of 47 possible, probable, or definite cases of Churg-Strauss syndrome and their 4,700 matched controls were identified and analyzed, Dr. Harrold said.
Compared with controls, patients were significantly more likely to have received a greater number of asthma drug classes overall, and to have been given prescriptions for oral steroids, inhaled steroids, and leukotriene modifiers.
On multivariate analysis, the number of asthma drug classes used within the previous 6 months and the use of leukotriene modifiers in the previous 2–6 months were not associated with Churg-Strauss syndrome. Only oral and inhaled steroids were associated with the syndrome, with odds ratios of 5.1 and 4.4, respectively.
The study was funded by GlaxoSmithKline.