scholarly journals Quantitative analysis of efficacy and safety of LABA/LAMA fixed-dose combinations in the treatment of stable COPD

2022 ◽  
Vol 16 ◽  
pp. 175346662110660
Author(s):  
Yiwen Gong ◽  
Yinghua Lv ◽  
Hongxia Liu ◽  
Qingshan Zheng ◽  
Lujin Li
Keyword(s):  
Adverse Events ◽  
Rescue Medication ◽  
Primary Outcome ◽  
Medication Use ◽  
Fixed Dose ◽  
Efficacy And Safety ◽  
Copd Exacerbations ◽  
Safety Outcomes ◽  
Secondary Outcomes ◽  
Long Acting

Objective: This study aimed to quantitatively compare the efficacy and safety of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations (FDCs) for the treatment of stable chronic obstructive pulmonary disease (COPD), especially in terms of their loss of efficacy in lung function. Methods: Randomized controlled clinical trials of LABA/LAMA FDCs for the treatment of stable COPD were comprehensively searched for in public databases. Pharmacodynamic models were established to describe the time course of the primary outcome [trough forced expiratory volume in the first second (FEV1)]. Secondary outcomes [COPD exacerbations, St. George’s Respiratory Questionnaire (SGRQ), Transition Dyspnoea Index (TDI), and rescue medication use] and safety outcomes [mortality, serious adverse events (SAEs), and withdrawals due to adverse events (AEs)] were also compared via a meta-analysis. Results: A total of 22 studies involving 16,486 participants were included in this study. The results showed that in terms of primary outcome (change from baseline in trough FEV1), the efficacy of vilanterol/umeclidinium was the highest, while the efficacy of formoterol/aclidinium was the lowest, with a maximum effect value (Emax) of 0.185 L [95% confidence interval (CI): 0.173–0.197 L] and 0.119 L (95% CI: 0.103–0.135 L), respectively. The efficacy of other drugs, such as formoterol/glycopyrronium, indacaterol/glycopyrronium, and olodaterol/tiotropium, were comparable, and their Emax values were 0.150–0.177 L. Except for vilanterol/umeclidinium, the other four LABA/LAMA FDCs showed a certain degree of loss of efficacy. Compared with the efficacy at 2 days, the trough FEV1 (L) relative to baseline at 24 weeks decreased by 0.029–0.041 L. In terms of secondary outcomes, the efficacy of different LABA/LAMA FDCs was similar in TDI and rescue medication use. However, formoterol/aclidinium was better in preventing the COPD exacerbations, while vilanterol/umeclidinium was the best in terms of SGRQ. In addition, different LABA/LAMA FDCs and placebo had similar safety outcomes. Conclusion: The present findings may provide necessary quantitative information for COPD medication guidelines.

Abstract 14373: Efficacy and Safety of Antihypertensive Drug Classes: The Systolic Blood Pressure Intervention Trial (SPRINT)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Christina Byrne ◽  
Anubodh Varshney ◽  
Zaid Almarzooq ◽  
Kristian H Kragholm ◽  
Maria L Krogager ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adverse Events ◽  
Systolic Blood Pressure ◽  
Antihypertensive Drug ◽  
Primary Outcome ◽  
Control Group ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Drug Classes ◽  
Safety Outcomes

Purpose: To assess the efficacy and safety of antihypertensive drug classes, including angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB), beta blockers (BB), calcium channel blockers (CCB), and thiazide diuretics (TD), in subjects at high cardiovascular (CV) risk. Methods: SPRINT was a randomized, controlled, open-label trial in which individuals without diabetes aged ≥50 years, at high CV risk, and with a systolic blood pressure (SBP) 130-180 mmHg were randomized to intensive (SBP target <120mmHg) or standard BP control (SBP target 135-139 mmHg). The primary outcome was the composite of acute coronary syndromes, stroke, heart failure, or CV death. Safety outcomes included serious adverse events, i.e., hypotension, syncope, electrolyte abnormalities, acute kidney injury or failure, and falls. Associations between baseline antihypertensive drug classes, efficacy, and safety outcomes, stratified by level of SBP control, were examined using Cox proportional-hazards regression. Results: Of 9361 participants, baseline use of antihypertensive agents was as follows: ACEi/ARB in 1317 (14%), BB in 911 (10%), CCB in 796 (9%), and TD in 979 (10%). A total of 1366 (15%) subjects did not have a record of being on an antihypertensive drug at baseline. In the intensive BP control group, use of a BB-based regimen at baseline was associated with a significantly higher risk of the primary outcome when compared with no medications ( Figure ). Similar patterns were observed for secondary efficacy endpoints. The risk of serious adverse events tended to be lower in patients receiving a treatment regimen containing either an ACEi/ARB or a TD compared with those receiving a regimen containing a BB or a CCB ( Figure ). Conclusions: In SPRINT, the risk of adverse events was lowest in patients who were not on an antihypertensive drug at baseline. ACEi/ARB-based and TD-based regimens appeared to have the best balance between efficacy and safety.

scholarly journals Efficacy and Safety of Azathioprine during Remission of Immune-Mediated Thrombotic Thrombocytopenic Purpura

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 773-773
Author(s):  
Christian Bichard ◽  
Ilaria Mancini ◽  
Pasquale Agosti ◽  
Pasqualina De Leo ◽  
Andrea Artoni ◽  
...  
Keyword(s):  
Adverse Events ◽  
Median Time ◽  
Clinical Remission ◽  
Primary Outcome ◽  
Clinical Relapse ◽  
Adamts13 Activity ◽  
Efficacy And Safety ◽  
Immune Mediated ◽  
Azathioprine Treatment ◽  
Secondary Outcomes

Abstract Introduction Acquired immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening thrombotic microangiopathy caused by the development of anti-ADAMTS13 autoantibodies. Up to 50% of patients surviving an acute iTTP event experience one or more relapses. Recent guidelines suggest treatment with rituximab in clinical remission in iTTP patients with low ADAMTS13 activity to prevent acute iTTP relapses. A 10% of cases who do not respond to rituximab or develop allergic reactions requiring therapy discontinuation have been reported. In these patients, azathioprine might be an alternative treatment to prevent acute iTTP relapses. The aim of this study was to assess the efficacy and safety of azathioprine treatment in iTTP patients in clinical remission. Methods We designed a retrospective cohort study including all iTTP patients treated with azathioprine during clinical remission, enrolled in the Milan TTP Registry between May 2003 and October 2020 and followed for at least six months. The efficacy of azathioprine was assessed in patients with at least four weeks of treatment. The primary outcome was clinical relapse during azathioprine treatment. The secondary outcomes were the partial and complete responses of ADAMTS13 (an ADAMTS13 activity increase above 20% and 45%, respectively) in patients with ADAMTS13 activity below 20% before azathioprine start. ADAMTS13 relapse (an ADAMTS13 activity decrease below 20%) in patients with a prior ADAMTS13 response was also assessed. As for the safety analysis, adverse events (AEs), associated or not with treatment discontinuation, were retrieved from clinical charts of all patients. Lastly, we assessed the association between variables such as sex, age, and concomitant autoimmune diseases, and ADAMTS13 response, using logistic regression models. Results We enrolled 43 patients with iTTP treated with azathioprine during clinical remission (Table 1). Forty-two percent of the patients had at least one concomitant autoimmune disease. The median exposure to azathioprine was 16 months (interquartile range [IQR] 8-49 months), the median dosage 1.3 mg/kg/day (IQR 0.9-1.6 mg/kg/day). Thirty-five cases were available for the primary outcome analysis (Table 2). Seven patients relapsed after a median time of 14 months after azathioprine start (IQR 8-58 months). The cumulative incidence of clinical relapse during azathioprine treatment was 10% at 1 year (95% Confidence Interval [CI] 0-21%), 22% at 2 years (95% CI 6-38%). Twenty-one cases were available for the secondary outcomes analysis. An ADAMTS13 partial response occurred in 10 patients (48%), after a median time of 3 months (IQR 3-9 months) after azathioprine start and lasted for a median time of 40 months (IQR 16-56 months). An ADAMTS13 complete response was achieved in 33% of patients, after a median time of 8 months (IQR 3-16 months) after azathioprine start and lasted for a median time of 16 months (IQR 0-53 months). Of the 10 responders, 3 (30%) had a subsequent ADAMTS13 relapse at 22, 24 and 37 months after azathioprine start. Adverse events were observed in 30% of patients, after a median time of 50 days after azathioprine start (IQR 26-331 days). Liver and pancreas alterations with increased levels of ALT, AST, GGT, ALP and lipase were the most frequent, followed by nausea and leukopenia (Table 3). In one patient, acute myeloid leukemia was diagnosed 6 months after azathioprine start. Fifteen percent of the patients had to stop the treatment due to AEs. No demographic or anamnestic variables were associated with ADAMTS13 response to azathioprine. Conclusions Forty-eight percent of patients attained an ADAMTS13 activity above 20%, with a durable response lasting more than 3 years, while adverse events were generally mild in nature. Azathioprine could be a valid and safe alternative in case of ineligibility or failure to respond to rituximab. Figure 1 Figure 1. Disclosures Mancini: Instrumentation Laboratory, Sanofi: Honoraria. Peyvandi: Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Sobi: Consultancy, Honoraria. OffLabel Disclosure: Azathioprine. It is an immunosuppressive drug used for the prevention of rejection in renal homotransplantation and for treatment of active rheumatoid arthritis.

scholarly journals The Outcomes of Nivolumab Fixed Dose 40 Mg Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-6
Author(s):  
Liudmila Fedorova ◽  
Kirill Lepik ◽  
Polina Kotselyabina ◽  
Elena Kondakova ◽  
Yuri Zalyalov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Progression ◽  
Hodgkin Lymphoma ◽  
Median Number ◽  
Fixed Dose ◽  
Published Data ◽  
High Dose ◽  
Efficacy And Safety ◽  
Classical Hodgkin Lymphoma ◽  
Grade 3

Background Currently, the recommended dose of nivolumab for patients with relapsed or refractory classical Hodgkin lymphoma (r/r сHL) is 3 mg/kg. Nevertheless, published clinical cases indicate the possible efficacy of lower doses of nivolumab. Moreover, experimental studies provided the rationale for possible reduction of nivolumab dose in patients with solid tumors (Agrawal et al. 2016). The presented data creates prerequisites for studying the lower nivolumab doses efficacy and safety in the r/r cHL therapy. Patients and Methods This study included 42 patients (14 male/28 female) with r/r cHL who were treated with nivolumab 40 mg every 2 weeks. The median age of patients was 36 (22-53) years. The median number of prior therapy lines was 4 (2-7). Prior treatment contained high dose chemotherapy with ASCT in 9 pts (21%), brentuximab vedotin in 14 pts (33%) and allo-HSCT in 1 pt (2%). Four pts (9,5%) had the partial response (PR) and the remaining 38 pts (90,5%) had the disease progression (PD) at the moment of nivolumab initiation. B-symptoms were present in 23 pts (55%), ECOG status was grade 0-I in 25 pts (59,5%), grade II in 12 pts (29%), grade III in 4 pts (9,5%) and grade IV in 1 pt (2%). The primary endpoint was the overall response rate (ORR) determined by positron-emission tomography/computed tomography (PET/CT) using LYRIC criteria every 3 months. Key secondary endpoints included progression-free survival (PFS) and overall survival (OS). Adverse events (AE) were evaluated according to CTCAE 4.03. The patient group characteristics were evaluated using descriptive statistics methods, the survival analysis was performed using Kaplan-Meyer method (SPSS Statistics v.17). Results The median number of nivolumab cycles was 24 (2-38). The response was evaluated in 41 out of 42 pts. The ORR was 66%. The best response included complete response (CR) in 39%, PR in 27%, stable disease in 5%, PD in 2%, indeterminate response (IR) in 27% of pts. With a median follow-up of 27,5 mo (11,3-34,5) 41 pts (97,6%) were alive, the median OS was not reached. The 2-year PFS was 44,5% (95% CI, 28,2-59,6) The nivolumab therapy was discontinued in 39 pts (93%) due to scheduled discontinuation in 14 pts (33%), PD in 13 pts (31%), grade 3-4 AE in 2 pts (5%), change of therapy because of insufficient response in 6 pts (14%) and other reasons in 4 pts (10%). The progression of disease during nivolumab therapy was present in 14 (33%) pts and after nivolumab discontinuation in 6 (14%) pts. After disease progression 30 pts (71%) were retreated with nivolumab monotherapy or in combination with chemotherapy. The median time to additional therapy was 14,5 mo (4,2 -32,9). The adverse events of any severity were observed in 30 pts (71%). Grade 3 or higher AE were present in 4 pts (9,5%), including grade 3 arthralgia, grade 3 anemia, grade 4 pneumonia and pneumonitis, grade 4 increased level of alanine aminotransferase and grade 5 MDS in 1 pt. A significant reduction of PD1+CD3+ cell population of peripheral blood lymphocytes was observed after first nivolumab cycle (median 0.7% (0-1.7) versus 33% (15.7-80.1) before therapy initiation, p = 0.02, Wilcoxon signed-rank test). Conclusion Our study demonstrated the efficacy and safety of nivolumab 40 mg therapy. The presented results are comparable to previously published data of nivolumab 3 mg/kg therapy in patients with r/r cHL. Thus, this creates a basis for further direct comparative study of nivolumab efficacy in different doses Disclosures No relevant conflicts of interest to declare.

scholarly journals LABA/LAMA fixed-dose combinations versus LAMA monotherapy in the prevention of COPD exacerbations: a systematic review and meta-analysis

2020 ◽  
Vol 14 ◽  
pp. 175346662093719
Author(s):  
Ching-Yi Chen ◽  
Wang-Chun Chen ◽  
Chi-Hsien Huang ◽  
Yi-Ping Hsiang ◽  
Chau-Chyun Sheu ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Similar Efficacy ◽  
Fixed Dose ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
History Of ◽  
Long Acting

Background: Long-acting muscarinic antagonist (LAMA) monotherapy is recommended for chronic obstructive pulmonary disease (COPD) patients with high risk of exacerbations. It is unclear whether long-acting β2-agonist (LABA)/LAMA fixed-dose combinations (FDCs) are more effective than LAMAs alone in preventing exacerbations. The aim of this study was to systematically review the literature to investigate whether LABA/LAMA FDCs are more effective than LAMA monotherapy in preventing exacerbations. Methods: We searched several databases and manufacturers’ websites to identify relevant randomized clinical trials comparing LABA/LAMA FDC treatment with LAMAs alone ⩾24 weeks. Outcomes of interest were time to first exacerbation and rates of moderate to severe, severe and all exacerbations. Results: We included 10 trials in 9 articles from 2013 to 2018 with a total of 19,369 patients for analysis in this study. Compared with LAMA monotherapy, LABA/LAMA FDCs demonstrated similar efficacy in terms of time to first exacerbation [hazard ratio, 0.96; 95% confidence interval (CI) 0.79–1.18; p = 0.71], moderate to severe exacerbations [risk ratio (RR), 0.96; 95% CI 0.90–1.03; p = 0.28], severe exacerbations (RR, 0.92; 95% CI 0.81–1.03; p = 0.15), and a marginal superiority in terms of all exacerbations (RR, 0.92; 95% CI 0.86–1.00; p = 0.04). The incidence of all exacerbation events was lower in the LABA/LAMA FDC group for the COPD patients with a history of previous exacerbations and those with a longer treatment period (52–64 weeks). Conclusion: This study provides evidence that LABA/LAMA FDCs are marginally superior in the prevention of all exacerbations compared with LAMA monotherapy in patients with COPD. The reviews of this paper are available via the supplemental material section.

scholarly journals 170 Efficacy and Safety of Dasotraline in Adults with Binge-Eating Disorder: A Randomized, Double-blind, Fixed-dose Trial

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 308-309
Author(s):  
Joyce Tsai ◽  
Brad Navia ◽  
Susan L McElroy ◽  
James I Hudson ◽  
Carlos M. Grilo ◽  
...  
Keyword(s):  
Eating Disorder ◽  
Adverse Events ◽  
Binge Eating ◽  
Binge Eating Disorder ◽  
Dry Mouth ◽  
Fixed Dose ◽  
Type I ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Dose Study

Abstract:Background:Dasotraline is a long-acting dopamine/norepinephrine reuptake inhibitor with a PK profile characterized by slow absorption and a t½ of 47-77 hours, permitting once-daily dosing. In a previous flexible dose study, dasotraline demonstrated significant efficacy in the treatment of binge-eating disorder (BED). The aim of this confirmatory fixed-dose study was to evaluate efficacy and safety of dasotraline in the treatment of patients with BED.Methods:Patients meeting DSM-5 criteria for BED were randomized to 12 weeks of double-blind treatment with dasotraline (4 mg/d or 6 mg/d), or placebo. The primary efficacy endpoint was change in number of binge-eating days per week at week 12. Secondary efficacy endpoints included changes at Week 12 on the Binge Eating Clinical Global Impression of Severity Scale (BE-CGI-S), the Yale-Brown Obsessive-Compulsive Scale Modified for Binge Eating (Y-BOCS-BE), and the proportion of patients with 100% cessation of binge-eating episodes during the final 4 weeks of treatment. Efficacy was assessed using an MMRM analysis (and a logistic regression model for cessation) with a pre-specified sequential testing procedure used to control overall type I error rate.Results:A total of 486 were in the ITT population (dasotraline 6 mg/d (N=162), 4 mg/d (N=161), or placebo (N=163). At week 12, treatment with dasotraline was associated with significant reduction in number of binge-eating days per week in the 6 mg/d group vs. placebo (-3.5 vs. -2.9; P=0.0045), but non-significant improvement in the 4 mg/d group vs. placebo (-3.2; P=0.12). Greater improvement was observed vs. placebo for dasotraline 6 mg/d and 4 mg/d, respectively, on the BE-CGI-S (P<0.01 and P<0.03) and the Y-BOC-BE (P<0.001 and P<0.02; all P-values were nominal, not adjusted for multiplicity). The proportion of patients who achieved 4-week cessation of binge-eating episodes was only significant for the dasotraline 6 mg in the completer population (P<0.05; post-hoc analysis) but was not significant for either dose of dasotraline vs. placebo when drop-outs were included in the analysis. The most common adverse events on dasotraline 6 mg/d and 4 mg/d were combined insomnia (early, middle, late), dry mouth, headache, decreased appetite, nausea, and anxiety. Changes in systolic and diastolic blood pressure were minimal. Mean baseline to endpoint changes in supine pulse rate on dasotraline 6 mg/d and 4 mg/d vs. placebo was +6.2 bpm and +4.8 vs. +0.2 bpm.Conclusions:In this 12-week, placebo-controlled, fixed-dose study, treatment with dasotraline 6 mg/d was associated with a significant reduction in frequency of binge-eating days per week; efficacy was not demonstrated for the 4 mg dose. Treatment with both doses of dasotraline resulted in improvement in the Y-BOCS-BE and the BE-CGI-S. Dasotraline was safe and generally well-tolerated at both doses; most common adverse events were insomnia, dry mouth and headache.Clinicaltrials.gov: NCT03107026Funding Acknowledgements:Supported by funding from Sunovion Pharmaceuticals Inc.

Implementation of a pharmacy consult service for evaluation of immune checkpoint inhibitor related adverse events at a large community hospital

2020 ◽  
pp. 107815522097026
Author(s):  
Jeff Kamta ◽  
Bren Magruder ◽  
Lisa Hymel
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Primary Outcome ◽  
Checkpoint Inhibitors ◽  
Delayed Presentation ◽  
Consult Service ◽  
Organ Systems ◽  
History Of ◽  
Secondary Outcomes

Introduction Immune checkpoint inhibitors (ICI) are novel oncolytic therapies associated with various immune related adverse events (irAEs) affecting multiple organ systems, which may have a delayed presentation. Identification of irAEs and prompt initiation of appropriate treatment represents a challenge to clinicians. The purpose of this study was to evaluate the effectiveness of a pharmacy consult service in identification and management of irAEs. Methodology: This was a single center, retrospective study. Patients included were: ≥18 years old, admitted as inpatients, and reported a history of cancer treatment within the last year. A pharmacy consult was developed and implemented for patients who reported a history of ICI therapy within the last year. Education regarding the consult service was provided to select physicians, nurses, and all pharmacists. Primary outcome: percent of admitted patients reporting ICI therapy within the last year, who required pharmacist intervention for an irAE. Secondary outcomes: types of interventions performed, percentage of recommendation acceptance, pharmacist time spent. Results Fifty-one patients received a pharmacy immunotherapy consult. Seventeen patients (33%) met the primary outcome. Thirty-three separate recommendations were made by pharmacists for these 17 patients. The secondary outcomes of interventions made and percentage accepted (n; % accepted): Initiation/adjustment of steroid therapy (20; 40%), placement of a consult for oncology or other specialist (10; 70%), other therapeutic interventions (3; 67%). Average time spent by pharmacist on initial consultations (SD): 29 minutes (15). Conclusion A pharmacy consult service may help to increase identification of patients receiving immune checkpoint inhibitors and initiate timely interventions.

Role of Breathing Exercises and Yoga/Pranayama in Childhood Asthma: A Systematic Review

2019 ◽  
Vol 15 (3) ◽  
pp. 175-183 ◽  
Author(s):  
Rashmi Ranjan Das ◽  
Jhuma Sankar ◽  
Sushil Kumar Kabra
Keyword(s):  
Lung Function ◽  
Adverse Events ◽  
Outcome Measures ◽  
Childhood Asthma ◽  
Primary Outcome ◽  
Immunological Parameters ◽  
Breathing Exercise ◽  
Breathing Exercises ◽  
Secondary Outcomes

Background: arious complementary or alternative medicines (including breathing exercises and yoga/pranayama) have been tried as an attractive option to pharmacotherapy in childhood asthma. Objective: To evaluate the role of breathing exercise and yoga/pranayama as add on therapy to the “pharmacologically recommended treatment” of childhood asthma. Methods: We searched the published literature in the major databases: Medline via Ovid, PubMed, CENTRAL, Embase, and Google Scholar till June 2018. Randomized trials comparing breathing exercises and yoga/ pranayama versus control or as part of a composite intervention versus control were included. The primary outcome measures were quality of life and change in asthma symptoms. Secondary outcomes were: decrease in medication use, number of exacerbations, change in lung function and immunological parameters, school absenteeism and adverse events. Results: A total of 10 trials (466 children, 6-14 years age) were included. The severity of asthma varied among the trials. The data for primary outcome measures could not be pooled, there were mixed results for both primary and secondary outcomes. No significant benefit was obtained in acute asthma and the lung function tests [except PEFR % at 4-6 weeks, PEF absolute at 3 months, and FVC absolute at 3 months] in chronic asthma. One trial compared breathing exercise versus yoga and found no difference. Adverse events were not significant. Conclusion: Breathing exercise and yoga/ pranayama may have some additive role in the treatment of childhood asthma. However, at present, it cannot be recommended as a standard of care due to insufficient data.

scholarly journals Long-acting muscarinic antagonists vs. long-acting β 2 agonists in COPD exacerbations: a systematic review and meta-analysis

2017 ◽  
Vol 43 (4) ◽  
pp. 302-312 ◽  
Author(s):  
Israel Silva Maia ◽  
Mariângela Pimentel Pincelli ◽  
Victor Figueiredo Leite ◽  
João Amadera ◽  
Anna Maria Buehler
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Therapeutic Effects ◽  
Muscarinic Antagonists ◽  
Serious Adverse Events ◽  
Exacerbation Rate ◽  
Copd Exacerbations ◽  
Long Acting

ABSTRACT Objective: To determine whether long-acting muscarinic antagonists (LAMAs) provide superior therapeutic effects over long-acting β2 agonists (LABAs) for preventing COPD exacerbations. Methods: This was a systematic review and meta-analysis of randomized clinical trials involving patients with stable, moderate to severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease criteria, treated with a LAMA (i.e., tiotropium bromide, aclidinium, or glycopyrronium), followed for at least 12 weeks and compared with controls using a LABA in isolation or in combination with a corticosteroid. Results: A total of 2,622 studies were analyzed for possible inclusion on the basis of their title and abstract; 9 studies (17,120 participants) were included in the analysis. In comparison with LABAs, LAMAs led to a greater decrease in the exacerbation rate ratio (relative risk [RR] = 0.88; 95% CI: 0.84-0.93]; a lower proportion of patients who experienced at least one exacerbation (RR = 0.90; 95% CI: 0.87-0.94; p < 0.00001); a lower risk of exacerbation-related hospitalizations (RR = 0.78; 95% CI: 0.69-0.87; p < 0.0001); and a lower number of serious adverse events (RR = 0.81; 95% CI: 0.67-0.96; p = 0.0002). The overall quality of evidence was moderate for all outcomes. Conclusions: The major findings of this systematic review and meta-analysis were that LAMAs significantly reduced the exacerbation rate (exacerbation episodes/year), as well as the number of exacerbation episodes, of hospitalizations, and of serious adverse events.

scholarly journals Evaluation of Inhaled Tobramycin in Early Eradication of Pseudomonas aeruginosa in Infants With Cystic Fibrosis

2020 ◽  
Vol 25 (8) ◽  
pp. 709-716
Author(s):  
Jane Choi ◽  
Kimberly Novak ◽  
Rohan Thompson
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Chronic Infection ◽  
Primary Outcome ◽  
Efficacy And Safety ◽  
Limited Data ◽  
Pseudomonas Aeruginosa Infection ◽  
Secondary Outcomes ◽  
Safety Assessments ◽  
First Time

OBJECTIVE Early antibiotic therapy has the potential to eradicate initial Pseudomonas aeruginosa infection and postpone chronic infection. There are limited data evaluating the efficacy and safety of inhaled tobramycin in patients with cystic fibrosis (CF) who are younger than 1 year. The objective of this study was to evaluate the effectiveness of inhaled tobramycin in early eradication of P aeruginosa in infants with CF. METHODS This retrospective study evaluated patients with CF younger than 1 year with first time infection with P aeruginosa. The primary outcome was the frequency of P aeruginosa eradication. Secondary outcomes were sustained culture negativity at 12 and 18 months and safety assessments. RESULTS Of 18 patients included in the study, 9 received inhaled tobramycin and an enteral fluoroquinolone and 9 received inhaled tobramycin alone. Microbiologic clearance of respiratory cultures was observed in 83% patients at end of therapy and 78% of patients at 1 month posttherapy. Eradication of P aeruginosa was observed in 56% of patients at 6 months posttreatment with sustained culture negativity observed in 39% of patients up to 18 months. CONCLUSIONS Inhaled-tobramycin therapy is effective in early eradication of P aeruginosa infection and is well tolerated in infants younger than 1 year.

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