ABSTRACT
BACKGROUND: The extrafine single inhaler triple therapy (efSITT) containing beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 µg has proved to be efficacious in patients with chronic obstructive pulmonary disease (COPD) in randomized control trials. OBJECTIVE: TRIWIN study evaluated the effectiveness of efSITT delivering beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 µg in COPD patients previously treated with multiple-inhaler triple therapy (MITT) in a real-world study in Greece. DESIGN: Prospective, multicenter, observational, non-interventional study was conducted over 24 weeks. METHODS: A total of 475 eligible patients had moderate-to-severe COPD, an indication for treatment with efSITT, and were symptomatic despite receiving MITT. COPD Assessment Test (CAT) score, pulmonary function parameters, use of rescue medication, and adherence to inhaler use were recorded at baseline (Visit 1), 3 (Visit 2), and 6 months (Visit 3) after treatment. RESULTS: Mean CAT score decreased from 21.4 points at Visit 1, to 16.6 at Visit 2 and 15.1 at Visit 3 (p < 0.001 for all pair comparisons). At Visit 3, 79.8% of patients reached a CAT improvement exceeding minimal clinically important difference (⩾2), compared to baseline. Mean forced expiratory volume in 1 s (%pred.) increased from 55.4% at Visit 1 to 63.5% at the end of study period (p < 0.001), while mean forced vital capacity (%pred.) increased from 71.1% at Visit 1, to 76.7% at Visit 3 (p < 0.001). The mean Test of Adherence to Inhalers score increased from 42.5 to 45.3 and 46.3 points, for the three visits, respectively (p < 0.001 comparing Visits 1/2 and Visits 1/3; p = 0.006 comparing Visits 2/3). The percentage of patients showing good adherence rose from 33.7% at baseline to 58.3% at Visit 3. The percentage of patients using rescue medication during the last month dropped from 16.2% to 7.4% at the end of study period (p < 0.001). Pulmonary function parameters also improved. CONCLUSION: The TRIWIN results suggest that extrafine beclomethasone dipropionate/formoterol fumarate/glycopyrronium is effective in improving health status, pulmonary function, and adherence and in reducing rescue medication use in COPD patients previously treated with MITT, in a real-world setting in Greece.
Subject(s)
Beclomethasone , Bronchodilator Agents , Drug Combinations , Formoterol Fumarate , Glycopyrrolate , Nebulizers and Vaporizers , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Male , Female , Aged , Prospective Studies , Middle Aged , Beclomethasone/administration & dosage , Beclomethasone/adverse effects , Administration, Inhalation , Formoterol Fumarate/administration & dosage , Treatment Outcome , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Glycopyrrolate/administration & dosage , Glycopyrrolate/adverse effects , Greece , Lung/physiopathology , Lung/drug effects , Severity of Illness Index , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/adverse effects , Time Factors , Forced Expiratory Volume , Medication Adherence , Glucocorticoids/administration & dosage , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/adverse effectsABSTRACT
Purpose: Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data. Patients and Methods: Patients with a recorded diagnostic COPD code who started BGF with ≥2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥70% (defined a priori). Results: Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV1: 54.5%), were highly symptomatic (mMRC ≥2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting ß2-agonist (SABA) over-use (≥3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period. Conclusion: The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days.
Subject(s)
Adrenergic beta-2 Receptor Agonists , Bronchodilator Agents , Databases, Factual , Glycopyrrolate , Primary Health Care , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Male , Female , Aged , Treatment Outcome , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Middle Aged , Time Factors , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/adverse effects , United Kingdom , Glycopyrrolate/administration & dosage , Glycopyrrolate/adverse effects , Budesonide, Formoterol Fumarate Drug Combination/administration & dosage , Budesonide, Formoterol Fumarate Drug Combination/adverse effects , Budesonide, Formoterol Fumarate Drug Combination/therapeutic use , Lung/physiopathology , Lung/drug effects , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/adverse effects , Drug Combinations , Retrospective Studies , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Aged, 80 and overABSTRACT
Purpose: To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany. Patients and Methods: Retrospective cohort study of patients with COPD and ≥1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015-31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting ß2-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-month pre-index period. Results: In total, 18,630 patients were identified as prevalent triple therapy users (MITT: 17,945; FF/UMEC/VI: 700; BDP/GLY/FOR: 908; non-mutually exclusive) and 2932 patients were identified as incident triple therapy initiators (MITT: 2246; FF/UMEC/VI: 311; BDP/GLY/FOR: 395; non-mutually exclusive). For both the prevalent and incident cohorts, more than two-thirds of patients experienced ≥1 moderate/severe exacerbation in the preceding 24 months; in both cohorts more BDP/GLY/FOR users experienced ≥1 moderate/severe exacerbation, compared with FF/UMEC/VI and MITT users. Overall, 97.9% of prevalent triple therapy users and 86.4% of incident triple therapy initiators received maintenance treatment in the 24-month pre-index period. Conclusion: In a real-world setting in Germany, triple therapy was most frequently used after maintenance therapy in patients with recent exacerbations, in line with current treatment recommendations.
Triple therapy (a combination of three different respiratory inhaled medications) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience repeated short-term symptom flare-ups when taking dual therapy (a combination of two different respiratory medications). Previously, patients had to take triple therapy using two or three separate inhalers. More recently, single-inhaler triple therapies have been developed, meaning patients can take all three different medications at the same time via one single inhaler. This study assessed the characteristics of patients who were already receiving triple therapy, or who started triple therapy (either via multiple inhalers or a single inhaler), in Germany between January 2015 and December 2019. In total, 18,630 patients who were already receiving triple therapy during the study period, and 2932 patients who newly started using triple therapy were included. The study reported that more than two-thirds of included patients had experienced at least one flare-up of COPD symptoms in the 2 years before starting triple therapy. Most patients had also received another therapy for COPD before starting triple therapy. A small proportion of patients started taking triple therapy after receiving no other therapy for COPD in the previous 2 years. The results of the study suggest that triple therapy for COPD in Germany is most often used in accordance with recommendations (patients already receiving therapy and experiencing repeated symptom flare-ups).
Subject(s)
Adrenergic beta-2 Receptor Agonists , Bronchodilator Agents , Drug Combinations , Glycopyrrolate , Muscarinic Antagonists , Nebulizers and Vaporizers , Pulmonary Disease, Chronic Obstructive , Humans , Male , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Female , Retrospective Studies , Germany , Aged , Administration, Inhalation , Middle Aged , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/adverse effects , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/adverse effects , Glycopyrrolate/administration & dosage , Glycopyrrolate/adverse effects , Chlorobenzenes/administration & dosage , Chlorobenzenes/adverse effects , Quinuclidines/administration & dosage , Quinuclidines/adverse effects , Treatment Outcome , Benzyl Alcohols/administration & dosage , Benzyl Alcohols/adverse effects , Beclomethasone/administration & dosage , Beclomethasone/adverse effects , Formoterol Fumarate/administration & dosage , Drug Therapy, Combination , Time Factors , Aged, 80 and overABSTRACT
Purpose: The TRITRIAL study assessed the effects of beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) fixed combination in patients with chronic obstructive pulmonary disease (COPD) in a real-world setting, focusing on patient's experience and perspective through the use of patients reported outcomes. Patients and Methods: TRITRIAL was a multicenter, prospective, observational study conducted on patients with moderate-severe COPD treated with BDP/FF/G fixed therapy for 12 months. The main objective was to evaluate the impact of BDP/FF/G on health status through the COPD Assessment Test (CAT) score. Additional assessments included adherence and satisfaction, measured by the TAI-10/12 questionnaire and a specifically designed eight-item questionnaire, quality of life through the EQ-5D-5L test, sleep quality through the COPD and Asthma Sleep Impact Scale (CASIS), as well as safety and disease-related outcomes. Results: Data from 655 patients were analyzed in the study. The mean total CAT score significantly improved (from 22.8 at baseline to 18.1 at 6 months and 16.5 at 12 months; p < 0.0001), as well as all the eight CAT sub-items, which decreased on average by 0.5-0.9 points during the study. Adherence and usability of the inhaler also improved during the study, with a decrease in poor compliance (from 30.1% to 18.3%) and an increase in good compliance (from 51.8% to 58.3%) according to the TAI score. Patients also benefited from significantly improved quality of life (EQ Index from 0.70 to 0.80; EQ-5D VAS score from 55.1 to 63.1) and sleep quality (CASIS score from 41.1 to 31.8). Finally, patients reported a significant reduction in exacerbation during the study. Conclusion: TRITRIAL showed that the BDP/FF/G fixed combination is effective and safe in patients with moderate-severe COPD and poorly controlled disease, improving patients' HRQoL, sleep quality, adherence and inhaler usability and reducing COPD symptoms and the risk of exacerbation in a real-life setting.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Quality of Life , Humans , Beclomethasone/adverse effects , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Glycopyrrolate/adverse effects , Prospective Studies , Health Status , Formoterol Fumarate/adverse effects , Fumarates , ItalyABSTRACT
PURPOSE: This study aimed to examine reports of cardiovascular adverse events (CV AEs) observed in the real-world during treatment with aclidinium, tiotropium, glycopyrronium, and umeclidinium alone or in combination with a LABA and, in the context of triple therapy, with the addition of an ICS, and submitted to the food and drug administration adverse event reporting system (FAERS). METHODS: A retrospective disproportionality analysis was conducted utilizing CV AE reports submitted to the FAERS from January 2020 to 30 September 2023. Disproportionality was measured by calculating the reporting odds ratio. RESULTS: Compared with ipratropium, tiotropium was associated with fewer reports of CV AEs. Compared with tiotropium, other LAMAs were more likely to be associated with reports of CV AEs. Combinations of glycopyrronium with indacaterol or formoterol and umeclidinium with vilanterol significantly reduced reports of CV AEs compared with the respective LAMA. The addition of an ICS to these combinations further reduced the risk of CV AE reports. CONCLUSION: Our study suggests that inhaled LAMAs are not free from cardiac AE risks. This risk may be more evident when the newer LAMAs are used, but it is generally significantly reduced when COPD patients are treated with dual bronchodilators or triple therapy. However, these results do not prove that LAMAs cause CV AEs, as FAERS data alone are not indicative of a drug's safety profile. Given the frequency with which COPD and cardiovascular disease co-exist, a large study in the general population could shed light on this very important issue.
Subject(s)
Cardiovascular Diseases , Pulmonary Disease, Chronic Obstructive , United States/epidemiology , Humans , Tiotropium Bromide/adverse effects , Glycopyrrolate/adverse effects , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/chemically induced , Retrospective Studies , United States Food and Drug Administration , Adrenergic beta-2 Receptor Agonists , Drug Combinations , Muscarinic Antagonists/therapeutic use , Bronchodilator Agents , Cardiovascular Diseases/chemically induced , Cardiovascular Diseases/epidemiology , Receptors, Muscarinic/therapeutic use , Administration, InhalationABSTRACT
Purpose: Triple therapy to prevent exacerbations from chronic obstructive pulmonary disease (COPD) is associated with improved health compared to single and dual-agent therapy in some populations. This study assessed the benefits of prompt administration of budesonide/glycopyrrolate/formoterol fumarate (BGF) following a COPD exacerbation. Patients and methods: EROS was a retrospective analysis of people with COPD using the MORE2 Registry®. Inclusion required ≥1 severe, ≥2 moderate, or ≥1 moderate exacerbation while on other maintenance treatment. Within 12 months following the index exacerbation, ≥1 pharmacy claim for BGF was required. Primary outcomes were the rate of COPD exacerbations and healthcare costs for those that received BGF promptly (within 30 days of index exacerbation) versus delayed (31-180 days) and very delayed (181-365 days). The effect of each 30-day delay in initiation of BGF was estimated using a multivariable negative binomial regression model. Results: 2409 patients were identified: 434 prompt, 1187 delayed, and 788 very delayed. The rate (95% CI) of total exacerbations post-index increased as time to BGF initiation increased: prompt 1.52 (1.39-1.66); delayed 2.00 (1.92-2.09); and very delayed 2.30 (2.20-2.40). Adjusting for patient characteristics, each 30-day delay in receiving BGF was associated with a 5% increase in the average number of subsequent exacerbations (rate ratio, 95% CI: 1.05, 1.01-1.08; p<0.05). Prompt initiation of BGF was also associated with lower post-index annualized COPD-related costs ($5002 for prompt vs $7639 and $8724 for the delayed and very delayed groups, respectively). Conclusion: Following a COPD exacerbation, promptly initiating BGF was associated with a reduction in subsequent exacerbations and reduced healthcare utilization and costs.
Subject(s)
Bronchodilator Agents , Pulmonary Disease, Chronic Obstructive , Humans , Bronchodilator Agents/adverse effects , Glycopyrrolate/adverse effects , Formoterol Fumarate/adverse effects , Retrospective Studies , Drug Combinations , Metered Dose Inhalers , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Double-Blind Method , Budesonide/adverse effects , Nebulizers and Vaporizers , Administration, InhalationABSTRACT
Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with significant morbidity and mortality and increased economic healthcare burden for patients with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) dual therapy is recommended for patients receiving mono-bronchodilator therapy who experience exacerbations or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), on moderate-to-severe exacerbation rates in patients with COPD in England. Patients and Methods: This retrospective cohort study used linked primary care electronic health record data (Clinical Practice Research Datalink-Aurum) and secondary care data (Hospital Episode Statistics) to assess outcomes for patients with COPD who had a first prescription for single-inhaler UMEC/VI or IND/GLY (index date) between 1 January 2015 and 30 September 2019 (indexing period). Analyses compared UMEC/VI and IND/GLY on moderate-to-severe, moderate, and severe exacerbations, healthcare resource utilization (HCRU), and direct costs at 6, 12, 18, and 24 months, and time-to-first on-treatment exacerbation up to 24 months post-index date. Following inverse probability of treatment weighting (IPTW), non-inferiority and superiority of UMEC/VI versus IND/GLY were assessed. Results: In total, 12,031 patients were included, of whom 8753 (72.8%) were prescribed UMEC/VI and 3278 (27.2%) IND/GLY. After IPTW, for moderate-to-severe exacerbations, weighted rate ratios were <1 at 6, 12, and 18 months and equal to 1 at 24 months for UMEC/VI; around the null value for moderate exacerbations and <1 at all timepoints for severe exacerbations. UMEC/VI showed lower HCRU incidence rates than IND/GLY for all-cause Accident and Emergency visits and COPD-related inpatient stays and associated all-cause costs at 6 months post-indexing. Time-to-triple therapy was similar for both treatments. Conclusion: UMEC/VI demonstrated non-inferiority to IND/GLY in moderate-to-severe exacerbation reduction at 6, 12 and 18 months. These results support previous findings demonstrating similarity between UMEC/VI and IND/GLY on reduction of moderate-to-severe exacerbations.
Subject(s)
Glycopyrrolate , Pulmonary Disease, Chronic Obstructive , Humans , Glycopyrrolate/adverse effects , Retrospective Studies , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Muscarinic Antagonists/adverse effects , EnglandABSTRACT
PURPOSE: Glycopyrronium, also known as glycopyrrolate, is an antimuscarinic competitive inhibitor of acetylcholine widely utilized topically for its anticholinergic properties in dermatology. A single topical glycopyrronium tosylate (GT) formulation is available on the market, and prescription of this medication has become increasingly popular among dermatologists. This medication has a relatively notable adverse effect profile and carries risks that patients need to be counseled on before initiation. SUMMARY: A 22-year-old female presented to our emergency department (ED) with a chief complaint of difficulty urinating for 48 hours and blurred vision for 2 weeks. Over the course of a week, she visited the ED once and urgent care multiple times due to complications associated with combination use of GT and cetirizine. Although these clinical effects were reversible, the patient impact in our case was profound given the time, cost, and invasive nature of these visits. CONCLUSION: The notable adverse effects of GT should be considered when prescribing this agent.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Hyperhidrosis , Mydriasis , Urinary Retention , Female , Humans , Young Adult , Adult , Glycopyrrolate/adverse effects , Mydriasis/chemically induced , Mydriasis/drug therapy , Urinary Retention/chemically induced , Urinary Retention/drug therapy , Hyperhidrosis/drug therapy , Hyperhidrosis/chemically inducedABSTRACT
INTRODUCTION: Severe sialorrhoea is a common, distressing problem in children/adolescents with neurodisabilities, which has adverse health and social consequences. The SALIVA trial is designed to evaluate the efficacy and safety of a paediatric-specific oral solution of glycopyrronium along with its impact on quality-of-life (QoL), which has been lacking from previous trials of sialorrhoea treatments. METHODS AND ANALYSIS: A double-blind, placebo-controlled, randomised phase IV trial is ongoing in several centres across France. Eighty children aged 3-17 years with severe sialorrhoea (≥6 on the modified Teachers Drooling Scale) related to chronic neurological disorders in whom non-pharmacological standard of care has already been implemented or has failed, will be recruited. Patients will be randomised 1:1 to receive a 2 mg/5 mL solution of glycopyrronium bromide (Sialanar 320 µg/mL glycopyrronium) or placebo three times daily during a 3-month blinded period. After Day 84, participants will be invited into a 6-month, open-label study extension period, where they will all receive glycopyrronium. The primary endpoint of the double-blind period will be the change from baseline to Day 84 in the Drooling Impact Scale (DIS), a validated measure to assess sialorrhoea. A series of secondary efficacy endpoints involving change in total DIS, specific DIS items and response (DIS improvement ≥13.6 points) will be analysed in a prespecified hierarchy. QoL data will be collected from parents, caregivers and patients where possible using specific DIS questions and DISABKIDS questionnaires. Safety endpoints, including adverse events, will be assessed throughout the trial periods. ETHICS AND DISSEMINATION: In total, 87 children have been recruited and recruitment is now complete. Final results are expected by the end of 2023. Findings will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT 2020-005534-15.
Subject(s)
Glycopyrrolate , Sialorrhea , Humans , Child , Adolescent , Glycopyrrolate/adverse effects , Sialorrhea/drug therapy , Sialorrhea/etiology , Saliva , Quality of Life , Treatment Outcome , Randomized Controlled Trials as Topic , Clinical Trials, Phase IV as TopicABSTRACT
INTRODUCTION: Air trapping is one of the main determinants of dyspnea in patients with chronic obstructive pulmonary disease (COPD). An increase in air trapping leads to a change in the normal diaphragmatic configuration with associated functional impairment. Said deterioration improves with bronchodilator therapy. Chest ultrasound (CU) has been used to assess changes in diaphragmatic motility after short-acting bronchodilator therapy, but there are no previous studies on these changes after long-acting bronchodilator treatment. MATERIAL AND METHODS: Interventional prospective study. Patients with COPD and moderate to very severe ventilatory obstruction were included in the study. Diaphragm motion and thickness were assessed by CU before and after 3 months of treatment with indacaterol/glycopirronium 85/43 mcg. RESULTS: Thirty patients were included (56.6% men, mean age: 69.4 ± 6.2 years). Pre- and post-treatment diaphragmatic mobility measured during resting breathing, deep breathing, and nasal sniffing were 19.9 ± 7.1 mm and 26.4 ± 8.7 mm (p < 0.0001); 42.5 ± 14.1 mm and 64.5 ± 25.9 mm (p < 0.0001); and 36.5 ± 17.4 mm and 46.7 ± 18.5 mm (p = 0.012), respectively. A significant improvement was also found in the minimum and maximum diaphragm thickness (p < 0.05), but there were no significant changes in the diaphragmatic shortening fraction after treatment (p = 0.341). CONCLUSIONS: Treatment with indacaterol/glycopyrronium 85/43 mcg every 24 hours for 3 months improved diaphragmatic mobility in patients with COPD with moderate to very severe airway obstruction. CU may be useful for assessing the response to treatment in these patients.
Subject(s)
Glycopyrrolate , Pulmonary Disease, Chronic Obstructive , Male , Humans , Middle Aged , Aged , Female , Glycopyrrolate/therapeutic use , Glycopyrrolate/adverse effects , Lung , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/adverse effects , Diaphragm/diagnostic imaging , Prospective Studies , Forced Expiratory Volume , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/chemically induced , Treatment OutcomeABSTRACT
BACKGROUND: The small airway disease has been recognized as a central feature of chronic obstructive pulmonary disease (COPD). Triple fixed combination beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) is provided as a pressurized single-dose inhaler based on an extra-fine formulation, which has been approved for patients with COPD experiencing frequent disease exacerbations. METHODS: The aim of our real-life single-center observational study was to investigate, in 22 patients with COPD, the effects of BDP/FF/G on lung function, respiratory symptoms, health status, and exacerbation rate. Several clinical and lung functional parameters were evaluated at baseline and after 12 months of treatment with combined inhaled triple therapy. RESULTS: With respect to baseline, after 12 months of treatment with BDP/FF/G, significant changes were recorded with regard to forced expiratory flow at 75% of forced vital capacity (FVC) (p < 0.01), forced expiratory flow at 50% of FVC (p < 0.01), forced expiratory flow at 25% of FVC (p < 0.05), and forced mid-expiratory flow between 25% and 75% of FVC (p < 0.01). Moreover, we observed reductions of total resistance (p < 0.01), effective resistance (p < 0.01), and effective specific resistance (p < 0.01). In the same period, residual volume diminished (p < 0.01) and forced expiratory volume in 1 s increased (p < 0.01). Moreover, in a subgroup of 16 patients, an enhancement of diffusion lung capacity (p < 0.01) was also detected. These functional results were paralleled by concomitant clinical effects, as evidenced by the improvements of modified British Medical Research Council (mMRC) dyspnea scale (p < 0.001), COPD Assessment Test (CAT) score (p < 0.0001), and COPD exacerbations (p < 0.0001). CONCLUSION: In conclusion, the valuable findings of our observational study consist in the corroboration in a real-life context of the therapeutic effects evidenced by randomized controlled trials with regard to the use of the triple inhaled BDP/FF/G therapy in patients with COPD.
Subject(s)
Beclomethasone , Pulmonary Disease, Chronic Obstructive , Humans , Formoterol Fumarate , Beclomethasone/adverse effects , Glycopyrrolate/adverse effects , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Bronchodilator Agents , Drug CombinationsABSTRACT
BACKGROUND: Primary axillary hyperhidrosis (PAHH) strongly affects the patient's quality of life. To date, topical treatment options are limited. One percent glycopyrronium bromide (GPB) showed promising efficacy and safety in a pivotal 4-week Phase 3a study. OBJECTIVES: To assess efficacy and safety of topical 1% GPB cream in patients with severe PAHH in a long-term study of 72 weeks versus baseline. METHODS: This was a long-term, open-label, Phase 3b trial for 72 weeks including 518 patients with severe PAHH. Patients were treated with 1% GPB cream once daily for 4 weeks, followed by a flexible dosing scheme (min. twice per week, max. once daily). Primary endpoint was the absolute change in sweat production from baseline to week 12. Further study endpoints included assessment of the severity of PAHH and the impact on quality of life. RESULTS: Total median sweat production decreased by 119.30 mg (-65.6%, both median) until week 12. Absolute change in sweat production from baseline to week 12 in logarithmic values was statistically significant (p < 0.0001). Patients' quality of life was improved at all study time points compared to baseline, as assessed by Hyperhidrosis Quality of Life Index and Dermatology Life Quality Index (p < 0.0001). Treatment was safe and locally well-tolerated with only few mild to moderate adverse drug reactions (ADRs). Dry mouth and application site erythema were the most common reported ADRs. CONCLUSIONS: Treatment with 1% GPB cream over 72 weeks significantly reduces sweat production and improves quality of life in patients with severe PAHH. One percent GPB cream is well-tolerated and provides an effective treatment option for long-term use in patients with severe PAHH.
Subject(s)
Glycopyrrolate , Hyperhidrosis , Humans , Glycopyrrolate/adverse effects , Quality of Life , Double-Blind Method , Hyperhidrosis/drug therapy , Treatment Outcome , Emollients/therapeutic useABSTRACT
Here, we report a case of unilateral ocular mydriasis in a pediatric patient with longstanding hyperhidrosis, as well as similar findings in her cat. The patient had been undergoing treatment of her hyperhidrosis with topical glycopyrrolate. This case highlights the potential side effect profile of topical antimuscarinics and the importance of counseling patients on proper precautions.
Subject(s)
Hyperhidrosis , Mydriasis , Female , Humans , Animals , Cats , Mydriasis/chemically induced , Mydriasis/drug therapy , Anisocoria/chemically induced , Anisocoria/drug therapy , Muscarinic Antagonists/adverse effects , Glycopyrrolate/adverse effects , Hyperhidrosis/chemically induced , Hyperhidrosis/drug therapyABSTRACT
Background: Rocuronium is an intermediate-acting non-depolarizing neuromuscular blocking agent frequently used in the emergency department for rapid sequence intubation. The prolonged effects of rocuronium may prevent the ability to conduct a meaningful neurological examination, thereby delaying appropriate diagnosis and treatment. Sugammadex and neostigmine are pharmacologic agents commonly used to reverse rocuronium. The safety of sugammadex versus neostigmine with glycopyrrolate for the reversal of rocuronium in the emergency department has not been well described. Objective: Evaluate the occurrence of hemodynamic instability post-administration of sugammadex versus neostigmine with glycopyrrolate in the emergency department for the reversal of rocuronium. Methods: A retrospective cohort study conducted among adult patients that received sugammadex or neostigmine with glycopyrrolate in the emergency department for the reversal of rocuronium. The primary outcome was occurrence of hemodynamic instability that required escalation of treatment. Secondary outcomes included occurrence of hypotensive, bradycardic, or cardiac arrest events. Results: A total of 37 patients met inclusion criteria (n = 10, sugammadex; n = 27, neostigmine). There was no difference between the two groups in regard to hemodynamic instability that required escalation of treatment within 30 minutes after receiving either sugammadex or neostigmine with glycopyrrolate (P = .557). Conclusion: There was no difference between the two groups in regard to occurrence of hemodynamic instability that required escalation of treatment. Given the small sample size, future studies are warranted to further delineate the safety of sugammadex and neostigmine with glycopyrrolate for the reversal of rocuronium in the emergency department.
Subject(s)
Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents , Adult , Humans , Sugammadex/adverse effects , Neostigmine/adverse effects , Rocuronium , Glycopyrrolate/adverse effects , Retrospective Studies , Neuromuscular Nondepolarizing Agents/adverse effects , Neuromuscular Blockade/adverse effects , Emergency Service, Hospital , HemodynamicsABSTRACT
Background: In the 52-week ETHOS study (NCT02465567), fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) reduced moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations versus fixed-dose long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) or inhaled corticosteroid (ICS)/LABA dual therapies. Here, ETHOS data were used to estimate the long-term cost-effectiveness of BGF versus LAMA/LABA and ICS/LABA dual therapies in the United Kingdom. Methods: Costs, exacerbations, quality-adjusted life-years (QALYs), and LYs were extrapolated using a Markov model that considered disease severity progression, risk of moderate and severe exacerbations, adverse events, and treatment discontinuation in patients with moderate-to-very severe COPD receiving BGF 320/14.4/10 µg, the LAMA/LABA glycopyrronium/formoterol fumarate dihydrate 14.4/10 µg (GFF), or the ICS/LABA budesonide/formoterol fumarate dihydrate 320/10 µg (BFF). Utilities for COPD severity states were estimated using EuroQol 5-dimension 5-level data from ETHOS. Exacerbation disutilities were sourced from published literature. Healthcare resource utilization was based on ETHOS data, published literature, key external experts' input, and informed assumptions. Unit costs came from the UK National Health Service Schedule of Reference Costs, Unit Costs of Health and Social Care from the Personal Social Services Research Unit, and published literature. A lifetime horizon was considered, with costs, QALYs, and LYs discounted at 3.5% per annum. Results: The incremental cost-utility ratio (ICUR; per QALY gained) was £9901 for BGF versus GFF and £2164 for BGF versus BFF. The probability of treatments being cost-effective at the conventional UK-adopted willingness-to-pay threshold of ICUR <£20,000 was 85.1% for BGF, 14.3% for GFF, and 0.6% for BFF. Conclusion: Based on ETHOS data, BGF was demonstrated to be cost-effective versus LAMA/LABA and ICS/LABA dual therapies at the conventional UK-adopted willingness-to-pay threshold (ICUR <£20,000). The main cost-effectiveness driver for BGF versus LAMA/LABA and ICS/LABA therapies was reduction in rate of exacerbations, which reduced costs and preserved quality of life.
Subject(s)
Glycopyrrolate , Pulmonary Disease, Chronic Obstructive , Humans , Glycopyrrolate/adverse effects , Cost-Benefit Analysis , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Quality of Life , State Medicine , Muscarinic Antagonists/adverse effects , Formoterol Fumarate/adverse effects , BudesonideABSTRACT
BACKGROUND: Goldenhar syndrome (GS) is a rare congenital disease characterized by impaired development of different facial structures and deformations of the teeth structures. Sialorrhea, which can cause difficulties in breathing and language impairment, is very common in GS and often difficult to treat. This case report highlights the short- and long-term importance of the therapeutic choice - glycopyrronium in oral solution - for the treatment of sialorrhea in children with poly-malformative syndrome, complicated by outcomes of post-hemorrhagic hydrocephalus. CASE PRESENTATION: We report the case of a 6-year-old child with GS, carrying a percutaneous endoscopic gastrostomy after tracheostomy. The child also presented developmental dysfunction of oral motor skills of feeding, complicated by severe sialorrhea, related to the maxillo-facial dysmorphism. Sialorrhea caused several respiratory tract infections and led to an increase in the care burden. Both the inoculations of botulinum toxin and the treatment with scopolamine transdermal patch have shown mild and transient efficacy. The therapeutic choice of glycopyrronium in oral solution was the most suitable for this patient, leading to long-term sialorrhea control. CONCLUSIONS: This clinical experience represents the first long-term efficacy and tolerability evaluation in using glycopyrrolate oral solution in treating drooling in children with GS. The reduction of drooling over time and the lack of clinically relevant adverse events have contributed to the decrease of respiratory tract infections, the development of oral motor skills, and determining a positive psycho-social impact on the patient's quality of life and her family.
Subject(s)
Goldenhar Syndrome , Respiratory Tract Infections , Sialorrhea , Child , Female , Glycopyrrolate/adverse effects , Glycopyrrolate/therapeutic use , Goldenhar Syndrome/chemically induced , Goldenhar Syndrome/complications , Goldenhar Syndrome/drug therapy , Humans , Quality of Life , Respiratory Tract Infections/drug therapy , Sialorrhea/drug therapy , Sialorrhea/etiologyABSTRACT
Objective: Chronic obstructive pulmonary disease (COPD) is a major and difficult disease of the chronic respiratory system that is common and frequent, with a huge disease burden. The aim of this study was to investigate the efficacy and safety of budesonide/glyburide/formoterol fumarate (BGF) in the treatment of COPD. Methods: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. The basic features of the seven pieces of literature were identified using the search strategy. The sample size range was 130â¼1264. Results: The effects of BGF increased FEV1 in patients with COPD (mean difference = 2.86, 95%CI: 2.71-3.01, p < 0.00001). The effects of BGF improved in patients with ≥1 TEAE in patients with COPD, and was not statistically significant after treatment (Odds rate = 1.00, 95%CI: 0.85-1.17, p=0.97). The effects of BGF increased in patients with TEAEs related a to study treatment in patients with COPD (odds rate = 1.27, 95% CI: 1.03-1.57, p=0.02). The effects of BGF in decreased patients with serious TEAEs in patients with COPD (odds rate = -0.02, 95% CI: -0.03--0.00, p=0.04). The effects of BGF decreased the death rate in patients with COPD, and were not statistically significant after treatment (odds rate = 0.77, 95% CI: 0.31-1.97, p=0.59). The effects of BGF decreased the hypertension rate in patients with COPD (odds rate = 0.92, 95% CI: 0.44-1.89, p=0.81), and was not statistically significant after treatment. The effects of BGF increased pneumonia in patients with COPD (odds rate = 1.55, 95% CI: 0.81-2.97, p=0.19), and were not statistically significant after treatment. The effects of BGF increased FEV1, increased patients with TEAEs related a to study treatment, and decreased patients with serious TEAEs in patients with COPD. Conclusion: This study elucidates the efficacy and safety of BGF in the treatment of COPD with a view to providing a clinical reference.
Subject(s)
Budesonide , Formoterol Fumarate , Glycopyrrolate , Pulmonary Disease, Chronic Obstructive , Aged , Bronchodilator Agents/adverse effects , Budesonide/adverse effects , Drug Combinations , Formoterol Fumarate/adverse effects , Glycopyrrolate/adverse effects , Humans , Pulmonary Disease, Chronic Obstructive/drug therapyABSTRACT
BACKGROUND: Facial hyperhidrosis (HH), a common problem with both cosmetic and psychological impact, interferes with quality of life. Wide range of treatment options is available for HH. Finding the most effective and yet a safe, tolerable option is the main target. OBJECTIVE: To evaluate and compare clinical efficacy, safety, and tolerability of topical 2% glycopyrrolate versus intradermal Botulinum toxin A injection in facial HH treatment. MATERIALS AND METHODS: Twenty-four patients with primary facial HH were randomly divided into 2 equal groups: Group A included patients treated by intradermal Botulinum toxin A injection and Group B included patients treated by topical glycopyrrolate gel 2%. Starch iodine test was performed before and after treatment to assess response, along with Hyperhidrosis Disease Severity Scale, Dermatology Life Quality Index (DLQI), and patient satisfaction. RESULTS: Both modalities showed complete response in 75% of cases with a longer duration of action in botulinum toxin group up to 6 months. Side effects were minor and temporary. Both Hyperhidrosis Disease Severity Scale and DLQI showed statistically significant improvement after treatment. CONCLUSION: Topical glycopyrrolate 2% showed comparable results to Botulinum toxin A in facial HH treatment with faster onset but shorter duration of action.
Subject(s)
Botulinum Toxins, Type A , Hyperhidrosis , Glycopyrrolate/adverse effects , Humans , Hyperhidrosis/drug therapy , Injections, Intradermal , Pilot Projects , Quality of Life , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
The single-inhaler extrafine formulation triple combination beclometasone dipropionate (BDP), formoterol fumarate (FF) plus glycopyrronium bromide (GB) is available for asthma management in adults. Its use in adolescents has not yet been evaluated. This study investigated the pharmacokinetic profile of BDP/FF/GB in adults and adolescents, with the aim of ruling out higher plasma exposure in adolescents compared to adults. In this open-label, non-randomized study, patients with asthma aged 12-17 (adolescents) and 18-64 years (adults) self-administered a single dose of BDP/FF/GB 400/24/50 µg via pressurized metered-dose inhaler (pMDI). The primary objective was to rule out higher systemic exposure to beclometasone 17-monopropionate (B17MP; active metabolite of BDP), formoterol, and GB in terms of the area under the plasma concentration-time curve from 0 to the last quantifiable concentration (AUC0-t ) in adolescents versus adults. A total of 40 adolescents and 40 adults entered the study (mean age of 14.8 and 43.6 years, respectively). The primary objective (AUC0-t ) was met, with the upper 90% confidence interval of the geometric mean ratio between adolescents and adults <125% for B17MP (point estimate 79.28 [90% CI 71.19; 88.29]), formoterol (88.68 [77.71; 101.20]) and GB (85.49 [72.96; 100.16]). All secondary pharmacokinetic endpoints supported the primary, with pharmacodynamic (safety) and tolerability results similar in the two populations. In conclusion, systemic exposure to extrafine BDP/FF/GB pMDI in adolescents was not higher than that in adults. Furthermore, there were no safety or tolerability signals to warrant a reduction in the dose of BDP/FF/GB for adolescents with asthma.