Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature

Adverse events triggered by non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drug-related intolerance reactions in medicine; they are possibly related to inhibition of cyclooxygenase-1. Coxibs, preferentially inhibiting cyclooxygenase-2, may therefore represent safe alternatives in patients with NSAID intolerance. We reviewed the literature in a systematic and structured manner to identify and evaluate studies on the tolerance of coxibs in patients with NSAID intolerance. We searched MEDLINE (1966–2006), the COCHRANE LIBRARY (4th Issue 2006) and EMBASE (1966–2006) up to December 9, 2006, and analysed all publications included using a predefined evaluation sheet. Symptoms and severity of adverse events to coxibs were analysed based on all articles comprising such information. Subsequently, the probability for adverse events triggered by coxibs was determined on analyses of double-blind prospective trials only. Among 3,304 patients with NSAID intolerance, 119 adverse events occurred under coxib medication. All adverse events, except two, have been allergic/urticarial in nature; none was lethal, but two were graded as life-threatening (grade 4). The two non-allergic adverse events were described as a grade 1 upper respiratory tract haemorrhage, and a grade 1 gastrointestinal symptom, respectively. In 13 double-blind prospective studies comprising a total of 591 patients with NSAID intolerance, only 13 adverse reactions to coxib provocations were observed. The triggering coxibs were rofecoxib (2/286), celecoxib (6/208), etoricoxib (4/56), and valdecoxib (1/41). This review documents the good tolerability of coxibs in patients with NSAID intolerance, for whom access to this class of drugs for short-term treatment of pain and inflammation is advantageous

Relation between bronchial responsiveness to inhaled leukotriene D(4) and markers of leukotriene biosynthesis

Background: While clinical trials with antileukotrienes have shown overall beneficial effects in asthma, the factors that determine leukotriene dependent asthma are still unclear. A study was undertaken to determine whether or not leukotriene responsiveness in the airways correlates with endogenous leukotriene biosynthesis. Methods: Bronchial responsiveness to leukotriene (LT) D(4) was assessed as PD(20)FEV(1) in 20 subjects with mild asthma and 10 healthy controls, and compared with bronchial responsiveness to methacholine and two global measures of leukotriene production—urinary LTE(4) and ex vivo production of LTB(4) in whole blood. Results: In patients with asthma the bronchoconstrictor activity of LTD(4) was about 1300 times greater than methacholine (geometric mean PD(20) 0.69 nmol v 887 nmol). Those who were most responsive to LTD(4) were relatively less responsive to methacholine (p<0.01). There was, however, no correlation between bronchial responsiveness to LTD(4) and urinary LTE(4) or blood ex vivo LTB(4) levels in asthmatic subjects or healthy controls. Subjects with asthma treated with inhaled corticosteroids produced higher levels of LTB(4) (p<0.05). Conclusions: General measures of leukotriene production cannot predict bronchial responsiveness to LTD(4). The unique bronchoconstrictive potency of LTD(4) on human airways may relate to the locally regulated expression of the cysteinyl LT(1) receptor