Tiotropium Respimat ® Versus HandiHaler ® : Comparison of Bronchodilator Efficacy of Various Doses in Clinical Trials

Abstract

Introduction

The long-acting muscarinic antagonist tiotropium bromide is approved in many countries as maintenance therapy for chronic obstructive pulmonary disease (COPD). Tiotropium is available as a dry-powder formulation delivered via HandiHaler^® (18 μg once daily) and is now also approved as an aqueous solution delivered via the Respimat^® Soft Mist™ Inhaler (5 μg once daily, 2 puffs of 2.5 µg). Several studies have compared the efficacy of tiotropium HandiHaler (18 μg once daily) with different doses of Respimat. We aimed to compare available bronchodilator efficacy data of once-daily Respimat 1.25, 2.5, 5, 10, 20 µg, and HandiHaler 18 µg to investigate which dose of tiotropium delivered by Respimat is the closest match to tiotropium HandiHaler.

Methods

Evaluation of six clinical trials (duration from 3 weeks to 2–3 years) that included lung function measures (trough forced expiratory volume in 1 s and trough forced vital capacity) as key outcomes.

Results

In the six trials, bronchodilator efficacy of Respimat 5 μg and HandiHaler 18 μg was similar; however, reduced bronchodilator efficacy was observed with lower doses of Respimat (1.25 and 2.5 μg).

Conclusion

These findings support the use of the marketed once-daily dose of Respimat 5 μg for the maintenance treatment of patients with COPD.

Funding

Boehringer Ingelheim.

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FP/FORM Versus FP/SAL Within Clinical Practice: An Updated Budget Impact Analysis in Asthma

Abstract

Introduction

Pressurized metered-dose inhalers (pMDI) such as fluticasone propionate and salmeterol (FP/SAL) are commonly used for the treatment of asthma in the UK. Previously, a budget impact analysis demonstrated that use of FP and formoterol fumarate (FP/FORM) pMDI as an alternative to FP/SAL pMDI, would be a cost-saving option for the UK National Health Service (NHS). This budget impact analysis aimed to update the existing analysis with prescription volume data and real-world evidence since the introduction of FP/FORM to the UK market.

Methods

Patient Data (IMS Information Solutions UK Ltd) moving annual total (MAT) August 2015 were used to ascertain the number of units of pMDI prescribed. Annual costs to the NHS in terms of drug, administration, monitoring and adverse event costs, were used to estimate the potential budget impact for FP/FORM and FP/SAL. Costs were calculated for current prescription volumes (12% FP/FORM, 88% FP/SAL), and for different prescription volume scenarios (FP/FORM at 0%, 25%, 50% and 100%). Real-world evidence and budget impact at a clinical commissioning group (CCG) level were also considered.

Results

Total annual costs per person year were less with FP/FORM (£625) than with FP/SAL (£734). Annual costs to the NHS based on the current prescription volumes and clinical trial data were estimated at £210.0M, however, based on real-world evidence, costs were estimated at £179.8M. For all scenarios with increased FP/FORM prescription volumes, the annual total costs to the NHS decreased. This was reflected at a CCG level.

Conclusion

The use of FP/FORM as an alternative to FP/SAL can result in cost savings for the NHS when assessing drug, administration, monitoring and adverse events costs. The inclusion of data released since the launch of FP/FORM within the budget impact analysis demonstrates that the potential cost savings to the NHS that were previously published are being translated to clinical practice.

Funding

Mundipharma, UK.

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Laparoscopic Sleeve Gastrectomy Improves Excessive Daytime Sleepiness and Sleep Quality 6 Months Following Surgery: A Prospective Cohort Study

Abstract

Introduction

Obstructive sleep apnea (OSA) is one of the most important co-morbid conditions related with morbid obesity. Bariatric procedures are associated with significant improvement in OSA. The aim of the current study was to evaluate the effect of bariatric surgery on daytime sleepiness and quality of sleep in patients that had undergone laparoscopic sleeve gastrectomy.

Methods

Fifty-nine patients were prospectively enrolled in the study. Pre-operative and post-operative (6 months) demographics, medical history, weight, and height of the patients were recorded, and patients were asked to complete Pittsburg Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaires. OSA screenings were performed using the STOP-Bang questionnaire.

Results

The mean age of the patients was 37.1 ± 1.2 years and 76% were female. Pre-operative and post-operative median (range) BMIs were 47 kg/m² (39–67 kg/m²) and 35 kg/m² (25–44 kg/m²), respectively (P < 0.001). The mean ± standard deviation excess weight loss was 51.6 ± 13.2%. In univariate analysis, total PSQI, STOP-Bang, and ESS scores were found to significantly improve 6 months after surgery (all P < 0.001). Multivariate mixed-model analysis showed a high correlation between the decrease in BMI and all key predictors. Mixed-model analysis revealed that every 1 kg/m² decrease in BMI was associated with a 0.32, 0.13, and 0.26 improvements in PSQI, STOP-Bang, and ESS scores, respectively (all P < 0.001).

Conclusion

Laparoscopic sleeve gastrectomy is associated with rapid weight loss and improvements in sleep quality, daytime sleepiness, and the risk of OSA 6 months after surgery.

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Prognostic significance of DSG3 in rectal adenocarcinoma treated with preoperative chemoradiotherapy

Future Oncology Ahead of Print.


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Age at Primary Malignancy Determines Survival in Adolescent and Young Adults That Develop a Secondary Thyroid Cancer

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Psychometric Analysis of the Three-Factor Eating Questionnaire-R18V2 in Adolescent and Young Adult-Aged Central Nervous System Tumor Survivors

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Inactivation of CYLD in intestinal epithelial cells exacerbates colitis-associated colorectal carcinogenesis - a short report

Abstract

Purpose

CYLD is a tumor suppressor that has been linked to the development of various human malignancies, including colon cancer. The tumor-suppressing function of CYLD is associated with its deubiquitinating activity, which maps to the carboxyl-terminal region of the protein. In the present study we evaluated the role of intestinal epithelial CYLD in colitis-associated cancer using a conditional mouse CYLD inactivation model.

Methods

In order to evaluate the role of CYLD in intestinal epithelial carcinogenesis, mice (IEC-Cyld ^Δ9 mice) that carry a mutation that eliminates the deubiquitinating domain of CYLD in intestinal epithelial cells (IEC) were generated by crossing Villin-Cre transgenic mice to previously generated mice carrying a loxP-flanked Cyld exon 9 (Cyld ^flx9 mice).

Results

We found that IEC-Cyld ^Δ9 mice did not present spontaneous intestinal abnormalities up to one year of age. However, upon challenge with a combination of genotoxic (AOM) and pro-inflammatory (DSS) agents we found that the number of adenomas in the IEC-Cyld ^Δ9 mice was dramatically increased compared to the control mice. Inactivation of CYLD in intestinal epithelial cells did not affect the classical nuclear factor-kappaB (NF-κB) and c-Jun kinase (JNK) activation pathways under physiological conditions, suggesting that these pathways do not predispose CYLD-deficient intestinal epithelia to colorectal cancer development before the onset of genotoxic and/or pro-inflammatory stress.

Conclusions

Our findings underscore a critical tumor-suppressing role for functional intestinal epithelial CYLD in colitis-associated carcinogenesis. CYLD expression and its associated pathways in intestinal tumors may be exploited for future prognostic and therapeutic purposes.

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