The leukotriene-receptor antagonist montelukast and the risk of Churg-Strauss syndrome: a case-crossover study

¹ Hôpital Cochin, Université Paris 5, Paris, France
² Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
³ Hôpital Cochin, UniversitéParis 5, Paris, France
⁴ University Hospital Zurich, Switzerland

^* To whom correspondence should be addressed. E-mail: amahr{at}bu.edu.

Accepted 27 January 2008

	Abstract

Background: There has been some concern that leukotriene-receptor antagonists might precipitate the onset of Churg-Strauss syndrome (CSS). Objective: To investigate the relationship between the leukotriene-receptor antagonist montelukast and CSS onset.

Methods: Medication histories of 78 CSS patients from France and Germany were retraced by questioning the patients, treating physicians and dispensing pharmacists, and from medical records. Using a case-crossover research design, we compared exposures to montelukast and other asthma medications during the 3-month 'index' period immediately preceding CSS onset with those of 4 previous 3-month 'control' periods. Odds ratios (OR) were computed by conditional logistic regression.

Results: OR (95% CI) for CSS onset were 4.5 (1.5-13.9) for montelukast, 3.0 (0.8-10.5) for inhaled long-acting ₂-agonists, 1.7 (0.5-5.4) for inhaled corticosteroids and 4.0 (1.3–12.5) for oral corticosteroids. Montelukast exposure during control periods increased temporally over 3 consecutive calendar periods of CSS onset from 1999 to 2003 (P_trend <.0001).

Conclusion: Montelukast use was associated with a 4.5-fold higher risk of CSS onset within 3 months. However, the positive estimates obtained for other long-term asthma-control medications suggest that this link is confounded by a general escalation of asthma therapy before CSS onset. The montelukast-CSS association observed herein is likely also explained by the increasing use of this medication over time.

Keywords: Churg�Strauss syndrome, asthma, leukotriene-receptor antagonists, montelukast, pharmacoepidemiology