Association of asthma therapy and churg-strauss syndrome: An analysis of postmarketing surveillance data

• Published in: Clinical therapeutics 2004-07, Vol.26 (7), p.1092-1104
• Main Authors: DuMouchel, William, Smith, Eric T., Beasley, Richard, Nelson, Harold, Yang, Xionghu, Fram, David, Almenoff, June S.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adrenal Cortex Hormones - administration & dosage; Adrenal Cortex Hormones - adverse effects; Adrenergic beta-Agonists - adverse effects; Adverse Drug Reaction Reporting Systems - statistics & numerical data; Allergies; Anti-Asthmatic Agents - administration & dosage; Anti-Asthmatic Agents - adverse effects; Anti-Asthmatic Agents - classification; Asthma; Asthma - complications; Asthma - drug therapy; Biological and medical sciences; Churg-Strauss; Churg-Strauss Syndrome - chemically induced; Churg-Strauss Syndrome - etiology; Data mining; Drug withdrawal; Humans; inhaled steroids; Leukotriene Antagonists - adverse effects; leukotriene receptor antagonists; Medical sciences; Pharmacology. Drug treatments; Pharmacovigilance; Polypharmacy; Product Surveillance, Postmarketing - methods; Product Surveillance, Postmarketing - statistics & numerical data; Steroids
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(04)90181-6

Background: Churg-Strauss syndrome (CSS), also known as allergic granulomatous angiitis (AGA), is a rare vasculitis that occurs in patients with bronchial asthma. The nature of the association of CSS with various asthma therapies is unclear. Objective: This study investigated the associations of different multidrug asthma therapy regimens and the reporting of AGA (the preferred code for CSS in the coding dictionary for the Adverse Event Reporting System [AERS]) by applying an iterative method of disproportionally analysis to th AERS database maintained by the US Food and Drug Administration. Methods: The public-release version of the AERS database was used to identify reports of AGA in patients receiving asthma therapy. Reporting of AGA was examined using iterative disproportionality methods in patients receiving ≥1 of the following drug classes: inhaled corticosteroid (ICS), leukotriene receptor antagonist (LTRA), short-acting β2-agonist (SABA), or long-acting β2-agonist (LABA). The Bayesian data-mining algorithm known as the multi-item gamma poisson shrinker was used to determine the relative reporting rates by calculation of the empirical Bayes geometric mean (EBGM) and its 90% CI (EB05 = lower limit and EB95 = upper limit) for each drug. Subset analyses were performed for each drug with different medication combinations to differentiate the relative reporting of AGA for each. Results: A strong association was found between LTRA use and AGA (EBGM = 104.0, EB05 = 95.0, EB95 = 113.8) that persisted with all combinations of therapy studied. AGA was also associated with the ICS, SABA and LABA classes (EBGM values of 27.8, 14.6 and 40.4, respectively). However, the latter associations were mostly dependent on the presence of concurrent LTRA and, to a lesser extemt, oral corticosteroid therapy and became negligible (ie, EB05 < 2) for patients who were not receiving these concurrent treatments. Conclusions: Differences based on relative reporting were observed in the patterns of association of AGA with LTRA, ICS, and β2-agonist therapies. A strong association between LTRA use and AGA was present regardless of the use of other asthma drugs.