Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new cutivate research articles will be listed here shortly after becoming available to us.
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Corticosteroids Suppress In vitro Tonsillar Proliferation in Children with Obstructive Sleep apnoea.
Eur Respir J. 2008 Dec 1;
Kheirandish-Gozal L, Serpero LD, Dayyat E, Kim J, Goldman JL, Snow A, Bhattacharjee R, Gozal D
Intranasal corticosteroids (CS) are potentially useful interventions for children with OSA, and may reduce lymphadenoid tissue size in the upper airway. We hypothesized that CS would reduce cellular proliferation and production of pro-inflammatory cytokines in a tonsil/adenoid mixed-cell culture system.Dissociated tonsils or adenoids harvested intra-operatively from children with polysomnographically-diagnosed OSA were cultured in control medium (CO) or after stimulation with LPS and concanavalin A (STIM), and incubated with dexamethasone (DEXA; 10(-5-)-10(-7)M), fluticasone (FLU; 10(-5)-10(-14)M), and budesonide (BUD; 10(-4)-10(-14) M). Proliferation and apoptosis were assessed, and supernatants were assayed for cytokines TNF-alpha, IL-6, and IL-8.STIM increased tonsillar and adenoidal proliferation compared to CO (1976+/-133 cpm vs. 404+/-69 cpm; pBUD>DEX (p
Inhaled corticosteroids in COPD: systemic effects of a local therapy?
Expert Opin Pharmacother. 2008 Dec; 9(18): 3271-3
Antoniu SA
Background: There are few data on the effects of inhaled corticosteroids on systemic inflammation in chronic obstructive pulmonary disease (COPD). Objective: Evaluation of the systemic anti-inflammatory effects of inhaled corticosteroids alone or in combination with long acting beta2-agonists. Methods: Analysis of the results of a randomized study assessing the short-term effects of inhaled fluticasone propionate, inhaled fluticasone + salmeterol and placebo on three inflammation biomarkers represented by C-reactive protein, IL-6 and surfactant protein-D. Results/conclusions: Inhaled corticosteroids alone or in combination exhibited partial systemic anti-inflammatory effects, reducing significantly only SP-D serum levels. Further evaluation of effects of inhaled corticosteroids on various biomarkers of systemic inflammation is required in more severe stable COPD.
Curr Med Res Opin. 2008 Dec; 24(12): 3571-82
Jung KS, Uh ST, Lee YC, Shim JJ, Park SK, Williams AE, Chan R
ABSTRACT Objectives: In the Asia-Pacific region there is a general preference for prescribing oral over inhaled medications for the treatment of asthma. This study compared inhaled salmeterol/fluticasone propionate therapy (SFC) with physician-determined current care (CC) in the management of persistent asthma in Korea. Methods: Adult patients with a documented history of reversibility in FEV(1) (>/= 12%) or PEF (>/= 15%), were randomised in a 2:1 ratio to unblinded treatment with SFC (50/250 mug bd or 50/500 mug bd) via Diskus (N = 284) or CC (N = 140) for 52 weeks. Morning peak expiratory flow (PEF) (primary endpoint), exacerbations, asthma symptoms and patient-reported outcome measures were recorded. Trial registration: GSK study number:100614. Results: At baseline, mean morning PEF in the SFC and CC group was 374 and 401 L/min respectively. The adjusted mean morning PEF at 52 weeks was 423 +/- 3 and 396 +/- 4 L/min for SFC and CC respectively (treatment difference of 27 +/- 5 in favour of SFC; 95% CI 17, 37; p < 0.0001). The mean rate of exacerbations over 52 weeks was significantly lower in the SFC group (SFC/CC odds ratio 0.57; 95% CI 0.44, 0.74; p < 0.0001). Treatment with SFC also resulted in a significantly greater improvement in asthma symptoms, in the number of patients assessed to have well controlled asthma (Asthma Control Test score >/= 20), and in a clinically significant improvement in overall Quality of Life. The incidence of adverse events was low and similar between the two groups and events were of the type expected in this population. Conclusions: The results of this open-label, randomised study showed that SFC provided greater asthma control than CC in the management of persistent asthma.
Curr Med Res Opin. 2008 Dec; 24(12): 3453-61
Tamminen K, Laine J, Soini E, Martikainen J, Kankaanranta H
ABSTRACT Background: Budesonide/formoterol maintenance and reliever therapy has shown its effectiveness as a treatment for moderate-to-severe asthma. Objective: To explore the cost-effectiveness of budesonide/formoterol maintenance and reliever therapy as compared to fixed combination therapies (budesonide/formoterol and salmeterol/fluticasone) with terbutaline as needed in the treatment of asthma in Finland. Methods: Patients without asthma exacerbations during a 6-month period were used as the effectiveness variable in the within-trial economic analysis. Finnish unit costs were applied to pooled resource use data, and multinomial cost-effectiveness plane and acceptability curves were formed based on bootstrapping. Results: Use of budesonide/formoterol maintenance and reliever therapy significantly reduced the rate of severe asthma exacerbations as compared with a fixed dose of budesonide/formoterol or salmeterol/fluticasone and terbutaline as needed. Total costs over 6 months were euro496 per patient for those who used the budesonide/formoterol maintenance and reliever therapy treatment model, which was euro78-101 lower than the cost of fixed combinations of salmeterol/fluticasone or budesonide/formoterol with terbutaline as needed. The results indicate that the budesonide/formoterol maintenance and reliever therapy achieves a high probability (> 93%) of cost effectiveness irrespective of willingness to pay level. Conclusions: Budesonide/formoterol maintenance and reliever therapy may be considered in the treatment of moderate-to-severe asthma instead of conventional treatment with combination products in view of its good clinical efficacy and a high probability of cost-effectiveness in the Finnish setting. However, a cost-effectiveness analysis with a longer time horizon, more Finnish-specific data, and ICS + short/long-acting inhaled beta(2)-agonist as an additional comparator is still warranted.
Curr Med Res Opin. 2008 Dec; 24(12): 3435-42
Delea TE, Stanford RH, Hagiwara M, Stempel DA
ABSTRACT Objective: To assess the association between adherence with fluticasone propionate/salmeterol combination (FSC) product in a single inhaler and asthma care utilization and costs in asthma patients in typical US clinical practice. Methods: Retrospective longitudinal analysis using linked medical and pharmacy claims from a managed care database representing >70 US health plans. Subjects included those with two prescriptions for FSC after January 1, 2000 (first prescription = 'index date') and diagnosis of asthma. Follow-up was defined as time from index date to disenrollment or discontinuation of FSC (180 days without supply), receipt of different controller, or 24 months post-index. Patients were excluded if:
Curr Med Res Opin. 2008 Dec; 24(12): 3393-403
Okubo K, Nakashima M, Miyake N, Uchida J, Okuda M
ABSTRACT Background: This study was designed to evaluate the efficacy and safety of fluticasone furoate nasal spray (FFNS), a novel enhanced-affinity intranasal corticosteroid, in Japanese patients with perennial allergic rhinitis (PAR), and to determine the optimal dose. Methods: In this phase II, multicenter, double-blind, randomized, placebo-controlled, parallel-group, dose-ranging study, 240 patients (aged >/= 16 years) received once-daily (od) treatment for 2 weeks with either FFNS 110 mug (n = 80), 220 mug (n = 81) or placebo (n = 79). Patients evaluated 3 nasal symptoms using a 4-point scale. Efficacy was assessed as the mean change from baseline in total nasal symptom score (TNSS). Results: Treatment with FFNS resulted in a significantly greater decrease over the treatment period in the mean 3TNSS (sneezing, rhinorrhea, and nasal congestion; p < 0.001 each dose vs. placebo), compared with placebo. More patients receiving FFNS had a markedly or moderately improved impression of treatment than placebo recipients (48% and 49% for FFNS 110 mug and 220 mug, respectively, vs. 18% for placebo; p < 0.001). Nasal rhinoscopy findings revealed significant improvements in mucosal swelling of the inferior turbinate (110 mug: p = 0.004; 220 mug: p = 0.011) and amount of watery rhinorrhea (110 mug: p = 0.003; 220 mug: p < 0.001), compared with placebo. Both doses of FFNS were well tolerated. Conclusions: Both FFNS 110 microg and 220 microg od were effective in alleviating nasal symptoms in Japanese patients with PAR over the 2-week duration of this study. FFNS 110 microg od was selected as the optimal dose for further evaluation in phase III clinical trials.
Respir Res. 2008 Nov 24; 9(1): 75
Hochhaus G
ABSTRACT: BACKGROUND: Pharmacokinetic properties, dosing regimen, and potency at the site of action are among the factors that influence activity of a corticosteroid. The potency of a corticosteroid at the site of action is determined significantly by its affinity to the glucocorticoid receptor. Recent literature on topical corticosteroids reveals an increasing emphasis on comparative relative receptor affinity values as a key method of differentiating among various corticosteroid compounds, particularly with regard to clinical efficacy. METHODS: A response was formulated to: Valotis A, Hogger P: Human receptor kinetics and lung tissue retention of the enhanced-affinity glucocorticoid fluticasone furoate. Respir Res 2007, 8:54. RESULTS: Relative receptor binding affinities, while often showing significant variability across different laboratories, are a valid parameter when a comparison of the pharmacological activity of various glucocorticoids at the site of action is desired. Unfortunately within this context, scientific literature including the article from Valotis and Hogger, confuse differences in potency (concentration or dose necessary to achieve a certain effect) with differences in efficacy (a quantitative difference in the overall maximum effect, even if all the receptors are occupied). All glucocorticoids will show the same efficacy as long as the selected dose will occupy the same number of receptors. CONCLUSIONS: While relative receptor affinities are useful for comparing in vitro potencies of corticosteroids, these data are not representative of physiologic conditions and should not be used as a basis for comparing the presumed effectiveness of compounds in a clinical situation.
Pharm Res. 2008 Oct 31;
Hoe S, Young PM, Chan HK, Traini D
PURPOSE: To introduce the design of the electrical Next Generation Impactor (eNGI), and validate its proposed function as a method of electrostatic characterization for pressurized metered dose inhaler (pMDI) formulations. METHODS: Flixotide(R) (fluticasone propionate), Ventolin(R) (salbutamol sulphate), and QVAR(R) (beclomethasone dipropionate) were used as model pMDIs in this study. At an airflow rate of 30 l/min, five individual actuations of each pMDI were introduced into the electrical low-pressure impactor (ELPI), Next Generation Impactor (NGI), and the eNGI. Charge profiles for each actuation were measured by the ELPI and eNGI, while mass profiles were recorded by the all three impactors. RESULTS: The difference in estimated mass median aerodynamic diameters and geometric standard deviations for all pMDIs using the NGI and eNGI were not found to be statistically significant (p < 0.05). The mean charge profiles from the ELPI and eNGI overlap well between 0.54 and 6.61 mum (Flixotide(R) and Ventolin(R)), and between 0.615 and 11.72 mum (QVAR(R)), where the majority of the impacted doses were collected. Conclusion: For the analysis of pMDIs, the eNGI is comparable to the NGI in measuring particle size distribution, while still being comparable to the ELPI in measuring charge distribution.
Clin Ther. 2008 Oct; 30(10): 1908-17
Friedman H, Wilcox T, Reardon G, Crespi S, Yawn BP
BACKGROUND: Asthma management guidelines state that a low-dose inhaled corticosteroid (ICS) is the preferred treatment for mild persistent asthma and that coadministration of a long-acting beta(2)-agonist (LABA) should be reserved for patients whose asthma is uncontrolled by single-entity ICS. However, it appears that many patients in the United States with mild persistent asthma are initially treated with combinations of fluticasone propionate/salmeterol (FPS). OBJECTIVE: The aim of this study was to examine whether use of FPS was consistent with asthma management guidelines. METHODS: A commercial insurance database was analyzed retrospectively to identify patients aged 12 to 62 years who had >or=1 pharmacy claim for FPS between October 1, 2004, and September 30, 2006. An index date corresponding to the date of the first FPS pharmacy claim was assigned to each patient. Medical and pharmacy claims data were analyzed for the 365-day period before the index date (preindex period). The severity of patients' asthma was inferred from their history of claims. Patients were identified as having more severe asthma if, during the preindex period, they either received >365 doses of short-acting beta(2)-agonists (SABAs), an oral corticosteroid (OCS), or an emergency department (ED) asthma visit with an OCS prescription, or were hospitalized for their asthma. RESULTS: Among 87,459 patients with new FPS claims, 60.8% were female, and the mean age was 37.3 years. Of these patients, 60,453 (69.1%) had no preindex ICS pharmacy claim or claims that would indicate moderate or severe asthma. In the preindex period, only 6.3% had received an ICS, 7.4% had >365 SABA doses, 22.7% had used an OCS, 1.1% had an ED visit with an OCS prescription, and 1.5% had been hospitalized. CONCLUSION: More than two thirds of the patients who initiated FPS treatment had neither received an ICS prescription before their first FPS pharmacy claim nor had evidence of asthma severity that would appear to warrant the use of an ICS/LABA combination.
J Allergy Clin Immunol. 2008 Oct; 122(4): 741-747.e4
Covar RA, Szefler SJ, Zeiger RS, Sorkness CA, Moss M, Mauger DT, Boehmer SJ, Strunk RC, Martinez FD, Taussig LM
BACKGROUND: Asthma exacerbations are a common cause of critical illness in children. OBJECTIVE: To determine factors associated with exacerbations in children with persistent asthma. METHODS: Regression modeling was used to identify historical, phenotypic, treatment, and time-dependent factors associated with the occurrence of exacerbations, defined by need for oral corticosteroids or emergency or hospital care in the 48-week Pediatric Asthma Controller Trial study. Children age 6 to 14 years with mild-to-moderate persistent asthma were randomized to receive either fluticasone propionate 100 microg twice daily (FP monotherapy), combination fluticasone 100 microg AM and salmeterol twice daily, or montelukast 5 mg once daily. RESULTS: Of the 285 participants randomized, 48% had 231 exacerbations. Using a multivariate analysis, which included numerous demographic, pulmonary, and inflammatory parameters, only a history of an asthma exacerbation requiring a systemic corticosteroid in the past year (odds ratio [OR], 2.10; P < .001) was associated with a subsequent exacerbation during the trial. During the trial, treatment with montelukast versus FP monotherapy (OR, 2.00; P = .005), season (spring, fall, or winter vs summer; P < or = .001), and average seasonal 5% reduction in AM peak expiratory flow (OR, 1.21; P = .01) were each associated with exacerbations. Changes in worsening of symptoms, beta-agonist use, and low peak expiratory flow track together before an exacerbation, but have poor positive predictive value of exacerbation. CONCLUSION: Children with mild-to-moderate persistent asthma with previous exacerbations are more likely to have a repeat exacerbation despite controller treatment. Inhaled corticosteroids are superior to montelukast at modifying the exacerbation risk. Available physiologic measures and biomarkers and diary card tracking are not reliable predictors of asthma exacerbations.