scholarly journals Down-titration from high-dose combination therapy in asthma: Removal of long-acting β2-agonist

2010 ◽  
Vol 104 (8) ◽  
pp. 1110-1120 ◽  
Author(s):  
Helen K. Reddel ◽  
Peter G. Gibson ◽  
Matthew J. Peters ◽  
Peter A.B. Wark ◽  
Ingrid B. Sand ◽  
...  
Keyword(s):  
Combination Therapy ◽  
High Dose ◽  
Dose Combination ◽  
Long Acting ◽  
Β2 Agonist

scholarly journals Cost-effectiveness of the fixed-dose combination tiotropium/olodaterol versus tiotropium monotherapy or a fixed-dose combination of long-acting β2-agonist/inhaled corticosteroid for COPD in Finland, Sweden and the Netherlands: a model-based study

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e049675
Author(s):  
Martine Hoogendoorn ◽  
Isaac Corro Ramos ◽  
Stéphane Soulard ◽  
Jennifer Cook ◽  
Erkki Soini ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
The Netherlands ◽  
Cost Effective ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Inhaled Corticosteroid ◽  
Dose Combination ◽  
Long Acting ◽  
Β2 Agonist ◽  
Country Specific

ObjectivesChronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-utility of the fixed dose combination of the bronchodilators tiotropium and olodaterol versus two comparators, tiotropium monotherapy and long-acting β2 agonist/inhaled corticosteroid (LABA/ICS) combinations, in three European countries: Finland, Sweden and the Netherlands.MethodsA previously published COPD patient-level discrete event simulation model was updated with most recent evidence to estimate lifetime quality-adjusted life years (QALYs) and costs for COPD patients receiving either tiotropium/olodaterol, tiotropium monotherapy or LABA/ICS. Treatment efficacy covered impact on trough forced expiratory volume in 1 s (FEV1), total and severe exacerbations and pneumonias. The unit costs of medication, maintenance treatment, exacerbations and pneumonias were obtained for each country. The country-specific analyses adhered to the Finnish, Swedish and Dutch pharmacoeconomic guidelines, respectively.ResultsTreatment with tiotropium/olodaterol gained QALYs ranging from 0.09 (Finland and Sweden) to 0.11 (the Netherlands) versus tiotropium and 0.23 (Finland and Sweden) to 0.28 (the Netherlands) versus LABA/ICS. The Finnish payer’s incremental cost-effectiveness ratio (ICER) of tiotropium/olodaterol was €11 000/QALY versus tiotropium and dominant versus LABA/ICS. The Swedish ICERs were €6200/QALY and dominant, respectively (societal perspective). The Dutch ICERs were €14 400 and €9200, respectively (societal perspective). The probability that tiotropium/olodaterol was cost-effective compared with tiotropium at the country-specific (unofficial) threshold values for the maximum willingness to pay for a QALY was 84% for Finland, 98% for Sweden and 99% for the Netherlands. Compared with LABA/ICS, this probability was 100% for all three countries.ConclusionsBased on the simulations, tiotropium/olodaterol is a cost-effective treatment option versus tiotropium or LABA/ICS in all three countries. In both Finland and Sweden, tiotropium/olodaterol is more effective and cost saving (ie, dominant) in comparison with LABA/ICS.

scholarly journals Combination Therapy with an SGLT2 Inhibitor as Initial Treatment for Type 2 Diabetes: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 8 (1) ◽  
pp. 45 ◽  
Author(s):  
Tamara Y. Milder ◽  
Sophie L. Stocker ◽  
Christina Abdel Shaheed ◽  
Lucy McGrath-Cadell ◽  
Dorit Samocha-Bonet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Combination Therapy ◽  
Low Dose ◽  
Meta Analysis ◽  
Sglt2 Inhibitor ◽  
Cochrane Library ◽  
High Dose ◽  
Dose Combination ◽  
Inhibitor Combination

Background: Guidelines differ with regard to indications for initial combination pharmacotherapy for type 2 diabetes. Aims: To compare the efficacy and safety of (i) sodium-glucose cotransporter 2 (SGLT2) inhibitor combination therapy in treatment-naïve type 2 diabetes adults; (ii) initial high and low dose SGLT2 inhibitor combination therapy. Methods: PubMed, Embase and Cochrane Library were searched for randomised controlled trials (RCTs) of initial SGLT2 combination therapy. Mean difference (MD) for changes from baseline (HbA1c, weight, blood pressure) after 24–26 weeks of treatment and relative risks (RR, safety) were calculated using a random-effects model. Risk of bias and quality of evidence was assessed. Results: In 4 RCTs (n = 3749) there was moderate quality evidence that SGLT2 inhibitor/metformin combination therapy resulted in a greater reduction in HbA1c (MD (95% CI); −0.55% (−0.67, −0.43)) and weight (−2.00 kg (−2.34, −1.66)) compared with metformin monotherapy, and a greater reduction in HbA1c (−0.59% (−0.72, −0.46)) and weight (−0.57 kg (−0.89, −0.25)) compared with SGLT2 inhibitor monotherapy. The high dose SGLT2 inhibitor/metformin combination resulted in a similar HbA1c but greater weight reduction; −0.47 kg (−0.88, −0.06) than the low dose combination therapy. The RR of genital infection with combination therapy was 2.22 (95% CI 1.33, 3.72) and 0.69 (95% CI 0.50, 0.96) compared with metformin and SGLT2 inhibitor monotherapy, respectively. The RR of diarrhoea was 2.23 (95% CI 1.46, 3.40) with combination therapy compared with SGLT2 inhibitor monotherapy. Conclusions: Initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.

scholarly journals Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2337-2346 ◽  
Author(s):  
MV Ragni ◽  
DA Amato ◽  
ML LoFaro ◽  
V DeGruttola ◽  
C Van Der Horst ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Combination Therapy ◽  
Cd4 Count ◽  
High Dose ◽  
Immunodeficiency Virus ◽  
Dose Combination ◽  
Hiv 1 ◽  
Asymptomatic Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus 1 ◽  
Asymptomatic Hiv

To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three different combinations of zidovudine (ZDV) and ddl in asymptomatic human immunodeficiency virus-1 (HIV-1) infection, we conducted an open-label, phase I/II study in 126 asymptomatic HIV-1-infected hemophilic and nonhemophilic subjects with a CD4 count of 200 to 500/mm3 stratified for prior zidovudine treatment and baseline CD4 count. Study arms included arm A, low-dose combination (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate-dose combination (ZDV 300 mg and ddI 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg, daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were no differences in toxicity between treatment arms (P = .51), nor were there any differences in the rate of development of clinical endpoints by treatment (P = .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A and D, 44/mm3 and 42/mm3, than arms B and C, 105/mm3 and 114/mm3, respectively, (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044) independently predicted weaker CD4 responses during the first 12 weeks of treatment. Using a regression model and adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative viral load from baseline by week 12 for all treatment arms combined (P = .0001), with significantly lower median percent reduction for arm A (56.3%) than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects, didanosine monotherapy and combination therapy with zidovudine are safe and effective in asymptomatic HIV-1-infected patients.

Effects of Dexamethasone and Oxymetazoline on “Postintubation Croup”: A ferret model

1987 ◽  
Vol 96 (6) ◽  
pp. 554-558 ◽  
Author(s):  
Charles I. Woods ◽  
Duncan S. Postma ◽  
Jiri Prazma ◽  
James Sidman
Keyword(s):  
Animal Model ◽  
Combination Therapy ◽  
Effective Treatment ◽  
High Dose ◽  
Laboratory Studies ◽  
Mucosal Ulceration ◽  
High Dose Dexamethasone ◽  
Reversible Lesion ◽  
Preliminary Study ◽  
Long Acting

Several studies recommend the use of steroids and racemic epinephrine for treatment of postintubation croup. Few controlled clinical or laboratory studies, however, support their effectiveness, and many questions remain about their use. The present study was undertaken to develop a reproducible animal model for postintubation croup and to perform initial controlled studies of the effects of dexamethasone (4 mg/kg) and the long-acting vasoconstrictor oxymetazoline (0.01 solution). An animal model for intubation trauma was developed with ten 10-week-old ferrets. Two models were created to reflect the spectrum of trauma—from simple mucosal contusion to mucosal ulceration. The first was to surgically strip mucosa in a circumferential manner at the level of the cricoid ring; the second was intubation trauma to the glottic and subglottic regions by use of a circular brush. Neither dexamethasone nor oxymetazoline had any statistically significant effect on subglottic edema in the mucosal stripping model. In the brush intubation model, oxymetazoline decreased subglottic edema at 2, 4, and 8 hours ( P < 0.05), while dexamethasone and combination therapy decreased edema at 2,4, 8, and 24 hours ( P < 0.05). At 24 hours, combination therapy was demonstrated to be the most effective in reducing subglottic edema. Oxymetazoline was as effective as dexamethasone and combination therapy at 2, 4, and 8 hours ( P < 0.05). In this preliminary study, we have established the potential usefulness of the brush intubation model for the study of this disorder. This model was shown to have a reproducible and reversible lesion. The mucosal stripping model was not shown to have reversible lesion and—while further study needs to be performed—may only be useful as a model for very severe cases of this disorder. These initial studies also demonstrated high-dose dexamethasone and oxymetazoline to be effective in treatment of subglottic edema secondary to mucosal trauma. They also indicate that combination therapy is a more effective treatment than either agent alone.

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