Inhaled corticosteroids plus salmeterol or montelukast: effects on resource utilization and costs.

Meyer JW.

Virginia Mason Clinic, Seattle, WA 98101, USA.

BACKGROUND: Experimental clinical studies have demonstrated that the addition of salmeterol to inhaled corticosteroids (ICSs) is superior to the addition of montelukast to ICSs. Observational research from real-world clinical practice is needed to confirm these results. OBJECTIVE: The present study was designed to assess, in clinical practice, the comparative impact on health care utilization and cost of 2 dual-controller therapies, ICS + salmeterol and ICS + montelukast. METHODS: This study involved the use of a 24-month pre/post retrospective design in patients continuously enrolled in any of 14 United HealthCare plans. Outcomes assessed were post-index pharmacy costs, rates of emergency department visits and hospitalizations, numbers of filled prescriptions for short-acting beta-agonists (SABAs), total asthma costs, and total health care costs. RESULTS: Subjects in the ICS + salmeterol group had 35% fewer post-index SABA claims than subjects in the montelukast add-on group (P <or=.05). Subjects using ICS + montelukast were 2.5 times more likely to have an asthma-related hospitalization than subjects using ICS + salmeterol (P <or=.065). Total adjusted asthma costs were 63% higher for the patients receiving ICS + montelukast than for the patients receiving ICS + salmeterol (P <or=.0001). In addition, total health care costs were 25% lower in the ICS + salmeterol group. (P <or=.0004). Additional reductions in hospitalization and emergency department visits were observed when the patients on FP + salmeterol were studied separately. CONCLUSION: In comparison with the use of montelukast and ICS, the use of salmeterol and ICS was associated with a significant reduction in SABA use, decreased hospital event rates, and significantly lower total asthma care costs.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11897987&dopt=Abstract montelukast, Singulair




Prevalence of serious eosinophilia and incidence of Churg-Strauss syndrome in a cohort of asthma patients.

Johnson ES.

Ingenix Epidemiology Division, Newton. Massachusetts 02466, USA.

BACKGROUND: Some leukotriene receptor antagonists, such as zafirlukast and montelukast, have been associated with systemic eosinophilia, with interest focused on Churg-Strauss syndrome (CSS). OBJECTIVE: To calculate the background incidence rate of CSS and prevalence of eosinophilia among people with asthma who have not used leukotriene receptor antagonists. METHODS: We conducted a cohort study in the setting of three geographically diverse UnitedHealthcare health plans. We identified 36,230 people who received a diagnosis of asthma during the period October 1994 through September 1997. We identified 241 potential cases from the claims data. Using a standardized hospital record abstract form, nurses abstracted relevant clinical data from the hospital charts of potential cases. We applied several a priori case definitions to the abstracted clinical data and computed incidence rates of CSS among patients with asthma. We additionally used these data to compute the prevalence of serious eosinophilia. RESULTS: Incidence rates of definite CSS among asthma patients ranged from zero (90% confidence interval 0.0 to 23.0) to 67 (90% confidence interval 22.5 to 160.6) cases per 1,000,000 person-years, depending on the definition used. All patients who met the criteria for CSS expressed symptoms consistent with mild asthma. CONCLUSIONS: This report is the first direct measurement of the incidence rate of CSS among asthma patients. We believe that the prevalence and incidence information that we report is a useful description of population rates in the United States for these conditions.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11926627&dopt=Abstract montelukast, Singulair




Leukotrienes mediate neurogenic inflammation in lungs of young rats infected with respiratory syncytial virus.

Piedimonte G.

Department of Pediatrics, University of Miami School of Medicine, Miami, Florida 33136, USA.

Respiratory syncytial virus (RSV) infection potentiates neurogenic inflammation in rat airways. Because some vascular effects of sensory nerves are mediated by cysteinyl leukotrienes (cysLTs), we studied whether the receptor antagonist montelukast inhibits neurogenic plasma extravasation in RSV-infected rats. Pathogen-free rats were inoculated at 2 wk (weanlings) or 12 wk (adults) of age with RSV or virus-free medium and treated with montelukast or its vehicle starting 1 day before inoculation. Five days postinoculation, we measured the extravasation of Evans blue-labeled albumin in the respiratory tract after stimulation of sensory nerves with capsaicin. Montelukast had no effect in the extrapulmonary airways but abolished albumin extravasation in the intrapulmonary airways of RSV-infected rats, with a larger effect in weanlings than in adults. Increased concentrations of 5-lipoxygenase-encoding mRNA and cysLTs, as well as numerous mast cells, were detected in the lung tissues of RSV-infected weanling rats. These observations suggest that the release of neuropeptides from capsaicin-sensitive sensory nerves and nonneuronal cells in the lungs of RSV-infected young rats increases vascular permeability by promoting the release of leukotrienes from mast cells.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11943681&dopt=Abstract montelukast, Singulair




[New horizons in the treatment of atopic dermatitis]

[Article in Spanish]

Ortiz De Frutos FJ.

Servicio de Dermatologia. Hospital 12 de Octubre. Madrid. Spain.

Nearly fifty years after their introduction, corticoids continue to be one of the main pillars of dermatological therapy in general and in atopic dermatitis in particular. However, their use is limited by local and systemic adverse effects.There is enormous demand for anti-inflammatory agents not belonging to the corticoid group that would be useful in the different inflammatory dermatoses.In the last few years the therapeutic arsenal for atopic dermatitis has increased with two distinct groups of drugs: topical immunomodulators and leukotriene inhibitors. Both groups of drugs are new and new compounds belonging to these types of drugs will probably appear in the next few years.Among the alternatives to corticoids are the immunomodulators and the most promising of these are macrolide antibiotics. Tacrolimus (FK 506) and pimecrolimus (ASM 981) belong to this group of substances with a high capacity to inhibit T lymphocyte activation. Although they also act on other cells playing a role in atopic dermatitis (mastocytes, Langerhans' cells, B lymphocytes) their action on T lymphocytes seems to be the most important. In T lymphocytes, these drugs act by inhibiting the action of calmodulin, a vital enzyme in the activation chain of these cells that ends in the production of interleukin 2 and other proinflammatory cytokines.The accumulated evidence of the various publications seems to indicate that tacrolimus is a safe and effective treatment of atopic dermatitis in patients aged 2 years or more. The drug was approved for clinical use 3 years ago in Japan and more than 1 year ago in the United States. The number of randomized clinical trials comparing this drug with placebo or various corticoids demonstrate that its action is overwhelming. Its anti-inflammatory action is similar to that of high-potency topical corticoids. Two doses daily are required and the drug has been tested in patients with moderate-to-severe atopic dermatitis. Published data from more than 10,000 patients guarantee its safety. The most frequent short-term adverse effect is a burning sensation in the site of application lasting a few minutes.Pimecrolimus has not yet been commercialized in any country and is currently undergoing phase III clinical investigations. It has been tested in three clinical trials in patients aged more than 3 months old with mild-moderate atopic dermatitis. Its safety profile is good and similar to that of tacrolimus.The number and quality of the data provided by studies of treatment with leukotriene inhibitors (zafirlukast, montelukast and zileuton) is much lower but these substances seem to warrant further investigation. Only five small series undergoing treatment with these products have been published.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11988144&dopt=Abstract montelukast, Singulair




Cysteinyl leukotrienes induce human eosinophil locomotion and adhesion molecule expression via a CysLT1 receptor-mediated mechanism.

Rossi GA.

Divisione di Pneumologia, G. Gaslini Institute, Genoa, Italy.

BACKGROUND: The mechanisms involved in eosinophil recruitment by cysteinyl-leukotrienes (CysLTs) remain to be defined. OBJECTIVE: We investigated whether CysLTs LTC4, LTD4 and LTE4 could directly stimulate in vitro adhesion molecule expression and cell locomotion of blood eosinophils from atopic asthmatic donors. METHODS: Mab staining and FACS analysis were used to evaluate Mac-1 and LFA-1 expression on eosinophils before and after CysLTs stimulation. Eosinophil locomotion was tested using a 48-well Boyden microchamber. RESULTS: CysLTs, at the concentrations of 1 and 10 nM, were able to significantly up-regulate Mac-1 expression (P < 0.05, each comparison) but not LFA-1 expression (P > 0.05, each comparison). A dose-dependent, eosinophil chemotaxis was also induced by LTC4, LTD4 and LTE4 (0.1-10 nM) (P < 0.01, each comparison). Montelukast (0.01 nM to 10 nM), a specific CysLT1 receptor antagonist, significantly down-regulated LTC4, LTD4 and LTE4-induced Mac-1 expression (P < 0.01, each comparison) and the CysLT-induced eosinophil migration (P < 0.01, each comparison). In contrast, montelukast did not affect Mac-1 expression or cell migration when eosinophils were stimulated by the 'non-specific activators', such as fMLP or C5a (P > 0.05, each comparison). CONCLUSION: These data demonstrate that CysLTs are active in vitro in directly up-regulating human eosinophil functions involved in eosinophil recruitment. The down-regulation of Mac-1 expression and eosinophil chemotaxis by the potent and selective CysLT1 receptor antagonist montelukast indicated the specificity of the LTC4-, LTD4- and LTE4-induced response.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11994100&dopt=Abstract montelukast, Singulair