Evaluating the effectiveness of asthma treatment in real-life practice.

Simnett S.

University Hospital Aintree, Liverpool, and The Royal College of Physicians of London, UK. Michaeal.pearson rcplondon.ac.uk

RATIONALE, AIMS AND OBJECTIVES: The randomized controlled trial (RCT) is considered the gold standard methodology for determining the efficacy and tolerability of new treatments. However, RCTs cannot provide information on the effectiveness of interventions as they are used in real life. This study was conducted to investigate the effectiveness of montelukast, a leukotriene receptor antagonist, in the real-world management of asthma, through a large-scale, retrospective, observational study: the National Montelukast Survey. METHODS: In order to ensure a robust methodology for the National Montelukast Survey we performed three pilot studies involving a total of almost 400 patients. During the pilots, the design of the study was extensively modified from a simple prescriber questionnaire used in the first pilot to the 'triangulated' methodology encompassing the perspectives of patient, prescriber and independent observer used in the National Montelukast Survey. Good levels of interobserver agreement confirmed the robustness of the final methodology. CONCLUSIONS: Achieving a robust methodology was dependent on the extensive piloting. It is possible to collect reliable observational data relating to treatment outcomes. We believe our methods are likely to have more widespread applicability and offer a potential improvement over postmarketing surveillance.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15189395&dopt=Abstract montelukast, Singulair




Asthma hospitalization risk and costs for patients treated with fluticasone propionate vs montelukast.

Kamal K.

Medstat Inc, Cambridge, Massachusetts 02140, USA. lucinda.orsini thomson.com

BACKGROUND: Inhaled corticosteroids have been shown to reduce rates of hospitalization and emergency department use compared with leukotriene receptor antagonists. OBJECTIVE: To examine differences in the probability of asthma-related hospitalizations, probability of switching or augmentin, with another therapy, and costs for patients treated with fluticasone propionate vs montelukast. METHODS: The study involved a 24-month retrospective analysis of patients with claims for asthma treatment (primary diagnosis International Classification of Disease, Ninth Revision code of 493.xx) between January 1, 1997, and June 30, 2000, and at least I outpatient pharmaceutical claim for fluticasone propionate (44 microg) or montelukast (5 or 10 mg). Univariate and multivariate analyses were used to determine the probability of asthma-related hospitalizations and switching or augmenting to another therapy, asthma costs, and total health care costs. Sensitivity analyses were conducted by replicating all of the analyses by age strata (ages 4-17 years and > or = 18 years) and varying lengths of follow-up. RESULTS: Patients receiving fluticasone propionate had a 62% lower risk of experiencing an asthma-related hospitalization within 1 year and a 44% lower risk of switching or augmenting to another asthma controller medication compared with montelukast. Asthma-related health care expenditures for montelukast patients were dollar 339 higher than for fluticasone propionate users (P < .001). Overall health care expenditures (asthma and nonasthma) were also dollar 1,197 higher in the montelukast group. CONCLUSIONS: Compared with montelukast-treated patients, patients treated with low-dose fluticasone propionate had a significantly lower risk of experiencing an asthma-related hospitalization, a lower risk of switching or augmenting with another controller, and significantly lower asthma and total health care costs.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15191020&dopt=Abstract montelukast, Singulair




[Urticaria paradoxically aggraved by H1 antihistamines]

[Article in French]

Nicolas JF.

Unite Immunologie Clinique et Allergologie, CHU Lyon-Sud, et INSERM U 503, IFR 128, 69495 Pierre-Benite Cedex, Lyon, France. amandine.lamy-catelain chu-lyon.fr

BACKGROUND: H1 antihistamines (anti-H1) are the treatment of choice in chronic urticaria. We report five cases of urticaria, induced or aggravated by H1 antihistamines. METHODS: The immunoallergological investigations included prick-tests and intradermal tests with the antihistamine responsible for acute urticaria. RESULTS: The skin tests confirmed the non-IgE dependent nature of the urticarial eruptions and anti-leukotrienes (montelukast, Singulair) were effective in controlling chronic urticaria in 3/4 patients. DISCUSSION: Two hypotheses are discussed to explain the paradoxical aggravating effect of H1 antihistamines on the urticaria: 1) the patients are sensitive to the toxic, pro-inflammatory effect of the drug, which is the source of nonspecific activation of mast cells; 2) the fact that the urticaria is sensitive to anti-leukotrienes suggests that histamine is not the principal mediator of urticaria in these patients.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15235532&dopt=Abstract montelukast, Singulair




Cost effectiveness of fluticasone propionate plus salmeterol versus fluticasone propionate plus montelukast in the treatment of persistent asthma.

Dorinsky P.

Department of Quality Management, Sharp Rees-Stealy Medical Group, San Diego, California 92101, USA. richard.oconnor sharp.com

BACKGROUND: Asthma is a chronic disease, the two main components of which are inflammation and bronchoconstriction. Fluticasone propionate (FP) and salmeterol, a strategy that treats both main components of asthma, has been recently compared with FP plus montelukast in a randomised clinical trial. The present study reports economic evaluation of these two strategies. OBJECTIVE: To determine the relative cost effectiveness when persistent asthma is treated with FP/salmeterol 100/50 microg twice daily administered via a single Diskus inhaler device versus treatment with FP 100 microg twice daily via a Diskus inhaler plus oral montelukast 10mg once daily. STUDY DESIGN: A cost-effectiveness analysis was performed by applying cost unit data to resource utilisation data collected prospectively during a US randomised, double-blind, 12-week trial of FP/salmeterol (n = 222) versus FP + montelukast (n = 225). Patients were > or =15 years of age and were symptomatic despite inhaled corticosteroid (ICS) therapy. PATIENTS AND METHODS: Efficacy measurements in this analysis included improvement in forced expiratory volume in 1 second (FEV(1)) and symptom-free days. Direct costs included those related to study drugs, emergency room department visits, unscheduled physician visits, treatment of drug-related adverse events (oral candidiasis), and rescue medication (salbutamol [albuterol]). The study assumed a US third-party payer's perspective with costs in 2001 US dollars. RESULTS: Treatment with FP/salmeterol resulted in a significantly higher proportion (p < 0.001) of patients who achieved a > or =12% increase in FEV(1) than treatment with FP + montelukast (54% [95% CI 47%, 61%] vs 32% [95% CI 26%, 38%]). Lower daily costs and greater efficacy of FP/salmeterol resulted in a cost-effectiveness ratio of US6.77 dollars (95% CI US5.99 dollars, US7.66 dollars) per successfully treated patient in the FP/salmeterol group compared with US14.59 dollars (95% CI US12.12 dollars, US17.77 dollars) for FP + montelukast. In addition, FP/salmeterol achieved similar efficacy in terms of symptom-free days compared with FP + montelukast (31% [95% CI 26%, 35%] vs 27% [95% CI 23%, 32%]), but at a significantly lower daily per-patient cost (US3.64 dollars [95% CI US3.60, US3.68 dollars] vs US4.64 dollars [95% CI US4.56 dollars, US4.73 dollars]). Sensitivity analyses demonstrated the stability of the results over a range of assumptions. CONCLUSION: From a US third-party payer's perspective, these findings suggest that treating the two main components of asthma (inflammation and bronchoconstriction) with FP/salmeterol may not only be a more cost-effective strategy but may actually lead to cost savings compared with the addition of montelukast to low-dose FP in patients with persistent asthma. The results were found to be robust over a range of assumptions.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15294013&dopt=Abstract montelukast, Singulair




Blockade of leukotriene B4 prevents articular incapacitation in rat zymosan-induced arthritis.

Cunha Fde Q.

Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceara, Rua Tiburcio Cavalcante, 2100/1201, Dionisio Torres, Fortaleza, Ceara Cep 60125-101, Brazil. arocha ufc.br

We investigated whether leukotrienes mediate cell influx and articular incapacitation in zymosan-induced arthritis. Rats received 1 mg zymosan intra-articularly (i.a.). The hyperalgesia was measured using the rat articular incapacitation test. Cell influx, leukotriene B(4) and prostaglandin E(2) levels were assessed in the joint exudate, at 6 h. Groups received either the leukotriene B(4) synthesis inhibitor MK 886 (3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl)]-2,2-dimethylpropanoic acid 30 min before or 2 h after the zymosan; 0.3-3 mg kg(-1) i.p.), the leukotrienes synthesis inhibitor BWA(4)C (N-(3-phenoxycinnamyl)-acetohydroxamic acid--2 h after the zymosan; 10 microg i.a.) or the peptido-leukotrienes antagonist sodium montelukast (30 min before and 2 h after the zymosan; 10 mg kg(-1) per os). MK 886 inhibited the articular incapacitation and cell influx, while reducing leukotriene B(4), but not prostaglandin E(2) levels. BWA(4)C inhibited the articular incapacitation. Sodium montelukast did not affect either of the parameters. The data suggest that leukotriene B(4) is involved in cell influx and articular incapacitation in zymosan arthritis.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15321738&dopt=Abstract montelukast, Singulair




Effects of antiasthmatic agents on the functions of peripheral blood monocyte-derived dendritic cells from atopic patients.

Kohno S.

Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.

BACKGROUND: Dendritic cells (DCs), the antigen-presenting cells in the airway, play a critical role in asthma. Nevertheless, there is little information on the effects of antiasthmatic agents on DCs. OBJECTIVES: The purpose of the present study was to determine the effects of representative antiasthmatic agents, including cysteinyl leukotriene (cysLT) 1 receptor antagonists, corticosteroid, and tacrolimus, on DCs in inducing allergy. METHODS: Human peripheral blood monocyte-derived DCs (MoDCs) generated from atopic and healthy subjects were pulsed with Dermatophagoides farinae allergen in the presence of medium alone, pranlukast, montelukast, dexamethasone, or tacrolimus. The mRNA expressions of cysLT receptor, cysLTs producing enzymes, and various surface markers on MoDCs, as well as the concentrations of cysLTs, IL-10, and IL-12 in cultured supernatants, were determined. MoDCs were also cocultured in vitro with autologous CD4(+) T cells, and IL-5 and IFN-gamma production was measured. RESULTS: MoDCs of atopic patients expressed mRNAs of cysLT1 receptor and cysLT-producing enzymes, and allergen pulsing significantly increased cysLT production. MoDCs of atopic patients showed a T(H)2-favoring phenotype and induced T(H)2-skewed cytokine production from autologous CD4(+) T cells. Dexamethasone and tacrolimus inhibited allergen-pulsed MoDC-induced cytokine production by autologous CD4(+) T cells without and with IL-10 inhibition, respectively. CysLT1 receptor antagonists had no effect on MoDC functions. CONCLUSION: Our results indicate that MoDCs of atopic patients induce a T(H)2 reaction. Corticosteroid and tacrolimus, but not cysLT1 receptor antagonists, inhibit T(H)2 reactions, and this effect is probably mediated through different pathways.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15356554&dopt=Abstract montelukast, Singulair




Effects of a cysteinyl leukotriene receptor antagonist on eosinophil recruitment in experimental allergic rhinitis.

Denburg JA.

Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

The cysteinyl leukotrienes (cysLTs) are potent lipid mediators in allergic disease, acting through a receptor (cysLT1-R) which can be targeted in rhinitis and asthma. We investigated the effects of cysLT1-R antagonism in experimental allergic rhinitis, focusing on bone marrow eosinophil progenitor responses. BALB/c mice were sensitized, then given daily intranasal ovalbumin for 2 weeks, with montelukast sodium (5 mg/kg or 2.5 mg/kg) or placebo by gavage. Bone marrow eosinophil/basophil colonies were enumerated, and colony cells were morphologically assessed as indices of eosinophil differentiation and maturation. Montelukast treatment resulted in a significant decrease of eosinophils in the nasal mucosa, and in either bone marrow interleukin (IL)-5-, but not IL-3-, or granulocyte-macrophage colony-stimulating factor-responsive eosinophil/basophil colony-forming units, and IL-5-stimulated eosinophil maturation. These results indicate that cysLT1-R antagonism in vivo limits both IL-5-responsive eosinophilopoiesis, acting at several stages of eosinophil differentiation and maturation. The anti-allergic effects of cysLT1-R antagonists are consistent with the concept that cysLTs and IL-5 act together in the recruitment of eosinophils and eosinophil progenitors from the marrow during upper airway allergic inflammation.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15379985&dopt=Abstract montelukast, Singulair