scholarly journals Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: a systematic review and meta-analysis

2018 ◽  
Vol 52 (6) ◽  
pp. 1801586 ◽  
Author(s):  
Mario Cazzola ◽  
Paola Rogliani ◽  
Luigino Calzetta ◽  
Maria Gabriella Matera
Keyword(s):  
Relative Risk ◽  
Combination Therapy ◽  
Meta Analysis ◽  
Blood Eosinophil ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
Bronchodilator Therapy ◽  
Long Acting ◽  
The Impact ◽  
Eosinophil Counts

We performed a meta-analysis to compare the impact of triple combination therapy with inhaled corticosteroids (ICS), long-acting β2-agonists (LABAs) and long-acting muscarinic receptor antagonists (LAMAs) versus LABA/LAMA combination therapy or single long-acting bronchodilator therapy in chronic obstructive pulmonary disease. The ICS/LABA/LAMA combination reduced the risk of exacerbation (relative risk 0.70, 95% CI 0.53–0.94) and improved trough forced expiratory volume in 1 s (mean difference in mL +37.94, 95% CI 18.83–53.89) versus LABA/LAMA combination therapy. The protective effect of triple combination therapy versus LABA/LAMA combination therapy against risk of exacerbation was greater in patients with blood eosinophil counts ≥300 cells·µL−1 (relative risk 0.57, 95% CI 0.48–0.68). While ∼38 patients had to be treated for 1 year with ICS/LABA/LAMA combination therapy to prevent one exacerbation compared to LABA/LAMA combination therapy, the number needed to treat (NNT) was ∼21 when compared to single long-acting bronchodilator therapy. The person-based NNT per year of ICS/LABA/LAMA combination therapy versus LABA/LAMA combination therapy was significantly (p<0.05) lower in patients with eosinophil counts ≥300 cells·µL−1 (NNT value: 8.58) than in those with counts <300 cells·µL−1 (NNT value: 46.28). The risk of pneumonia did not differ between ICS/LABA/LAMA combination therapy and its comparators. The number needed to harm was ∼195. This meta-analysis suggests that patients on single long-acting bronchodilator therapy or LABA/LAMA combination therapy, who still have exacerbations and have blood eosinophil counts ≥300 cells·µL−1, could benefit from ICS/LABA/LAMA combination therapy.

Triple therapy in uncontrolled asthma: a network meta-analysis of Phase III studies

2021 ◽  
pp. 2004233
Author(s):  
Paola Rogliani ◽  
Beatrice Ludovica Ritondo ◽  
Luigino Calzetta
Keyword(s):  
Meta Analysis ◽  
Phase Iii ◽  
Fixed Dose ◽  
High Dose ◽  
Severe Exacerbation ◽  
Triple Combination ◽  
Combination Therapies ◽  
Uncontrolled Asthma ◽  
Long Acting ◽  
The Impact

Conflicting evidence is currently available concerning the impact on asthma exacerbation of triple inhaled corticosteroid (ICS), long-acting β2-adrenoceptor agonist (LABA), and long-acting muscarinic receptor antagonist (LAMA) fixed-dose combination (FDC). Since meta-analyses allow settling controversies of apparently inconsistent results, we performed a network meta-analysis of Phase III randomised controlled trials including 9535 patients to assess the effect of ICS/LABA/LAMA combinations in uncontrolled asthma. Triple combination therapies with an ICS administered at high dose (HD) were more effective (p<0.05) than medium dose (MD) ICS/LABA/LAMA FDC and both MD and HD ICS/LABA FDCs against moderate to severe exacerbation (relative risk [RR] from 0.61 to 0.80) and increasing trough forced expiratory volume in the 1st second (mL from +33 to +114). Triple combination therapies including HD ICS were superior (p<0.05) than MD ICS/LABA/LAMA FDC in preventing severe exacerbation (RR from 0.46 to 0.65), but not with respect to moderate exacerbation (p>0.05). Triple combination therapies were equally effective on asthma control, with no safety concerns. This quantitative synthesis suggests that ICS/LABA/LAMA FDCs are effective and safe in uncontrolled asthma, and that the dose of ICS in the combination represents the discriminating factor to treat patients with a history of moderate or severe exacerbation.

scholarly journals Triple Combination Therapy With PD-1/PD-L1, BRAF, and MEK Inhibitor for Stage III–IV Melanoma: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ye Liu ◽  
Xilan Zhang ◽  
Guoying Wang ◽  
Xinchang Cui
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Adverse Events ◽  
Meta Analysis ◽  
Stage Iii ◽  
Controlled Trials ◽  
Triple Combination ◽  
Triple Combination Therapy ◽  
Randomized Controlled

Triple combination of anti-PD-1/PD-L1 immunotherapy and anti-BRAF plus anti-MEK targeted therapy is a promising antitumor strategy and is increasingly being used in clinical trials. To evaluate the safety and efficacy of triple combination of PD-1/PD-L1, BRAF, and MEK inhibition in patients diagnosed with stage III-IV melanoma, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs). The PubMed, EMBASE, and Cochrane Library were searched for all studies published from inception to January 2021. The progression free survival (PFS), overall survival (OS), overall response rate (ORR), and risk of adverse events (AEs) were extracted by two independent investigators and pooled hazard ratio (HR) or risk ratio (RR) with 95% CI were determined using the random-effects model for data synthesis. Overall, five randomized controlled trials encompassing 1,266 patients with stage III-IV melanoma were selected. Triple combination therapy significantly improved PFS (HR = 0.71; 95% CI = 0.59 to 0.86; P = 0.0005) and 2-year OS (RR = 1.12; 95% CI = 1.03 to 1.23; P = 0.01), but had no impact on ORR (RR = 1.09; 95% CI = 0.91 to 1.30; P = 0.37) when compared with controlled treatment group. In addition, triple combination therapy was associated with increased risks of hypothyroidism, arthralgia, myalgia, ALT increased, AST increased, asthenia, and pyrexia compared with control group. Triple combination therapy of PD-1/PD-L1, BRAF, and MEK inhibition achieved better survival benefits but had higher incidence of some adverse events over two-drug combination or monotherapy. Further randomized controlled clinical trials are needed to verify our results.Systematic Review RegistrationPROSPERO 2021 CRD42021235845 Available from https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235845.

scholarly journals Escalation Time to Open Triple Combination Therapy from the Initiation of LAMA versus ICS/LABA in COPD Management: Findings from Comparing the Incidence of Tiotropium and ICS/LABA in Real-World Use in South Korea (CITRUS) Study

2021 ◽  
Vol 11 (12) ◽  
pp. 1325
Author(s):  
Ye Jin Lee ◽  
Chin Kook Rhee ◽  
Yong Il Hwang ◽  
Kwang Ha Yoo ◽  
So Eun Lee ◽  
...  
Keyword(s):  
Combination Therapy ◽  
South Korea ◽  
Triple Therapy ◽  
Inhaled Corticosteroids ◽  
Chronic Obstructive ◽  
Triple Combination ◽  
Obstructive Pulmonary Disease ◽  
Triple Combination Therapy ◽  
Copd Patients ◽  
Long Acting

Background: bronchodilators are the key treatment for chronic obstructive pulmonary disease (COPD), however, inhaled corticosteroids (ICSs)/long-acting β2-agonists (LABA) are widely prescribed. We compared the escalation time to open triple combination therapy between long-acting muscarinic receptor antagonists (LAMA) and ICS/LABA in COPD management. Methods: this retrospective study included COPD patients selected from the National Health Insurance Service of South Korea from January 2005 to April 2015. The primary outcome was the escalation time to triple therapy in patients who initially received LAMA or ICS/LABA. Other outcomes included risk factors predisposing escalation to triple combination therapy. Results: a total of 2444 patients were assigned to the LAMA or ICS/LABA groups. The incidences of triple combination therapy in the LAMA and ICS/LABA groups were 81.0 and 139.8 per 1000 person-years, respectively (p < 0.001); the median times to triple therapy escalation were 281 and 207 days, respectively (p = 0.03). Treatment with ICS/LABA showed a higher risk of triple therapy escalation compared to LAMA (hazard ratio (HR), 1.601; 95% confidence interval (CI), 1.402–1.829). The associated risk factor was male sex. (HR, 1.564; 95% CI, 1.352–1.809). Conclusions: the initiation of COPD treatment with LAMA is associated with a reduced escalation time to triple therapy compared with ICS/LABA.

scholarly journals Impact of cardiovascular disease and risk factors on fatal outcomes in patients with COVID-19 according to age: a systematic review and meta-analysis

Heart ◽  
2020 ◽  
pp. heartjnl-2020-317901
Author(s):  
SungA Bae ◽  
So Ree Kim ◽  
Mi-Na Kim ◽  
Wan Joo Shim ◽  
Seong-Mi Park
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Relative Risk ◽  
Elderly Patients ◽  
Meta Analysis ◽  
Fatal Outcome ◽  
Young Patients ◽  
Lower Prevalence ◽  
Prevalence Rates ◽  
The Impact

ObjectivePrevious studies that evaluated cardiovascular risk factors considered age as a potential confounder. We aimed to investigate the impact of cardiovascular disease (CVD) and its risk factors on fatal outcomes according to age in patients with COVID-19.MethodsA systematic literature review and meta-analysis was performed on data collected from PubMed and Embase databases up to 11 June 2020. All observational studies (case series or cohort studies) that assessed in-hospital patients were included, except those involving the paediatric population. Prevalence rates of comorbid diseases and clinical outcomes were stratified by mean patient age in each study (ranges: <50 years, 50–60 years and ≥60 years). The primary outcome measure was a composite fatal outcome of severe COVID-19 or death.ResultsWe included 51 studies with a total of 48 317 patients with confirmed COVID-19 infection. Overall, the relative risk of developing severe COVID-19 or death was significantly higher in patients with risk factors for CVD (hypertension: OR 2.50, 95% CI 2.15 to 2.90; diabetes: 2.25, 95% CI 1.89 to 2.69) and CVD (3.11, 95% 2.55 to 3.79). Younger patients had a lower prevalence of hypertension, diabetes and CVD compared with older patients; however, the relative risk of fatal outcomes was higher among the former.ConclusionsThe results of the meta-analysis suggest that CVD and its risk factors (hypertension and diabetes) were closely related to fatal outcomes in COVID-19 for patients across all ages. Although young patients had lower prevalence rates of cardiovascular comorbidities than elderly patients, relative risk of fatal outcome in young patients with hypertension, diabetes and CVD was higher than in elderly patients.Prospero registration numberCRD42020198152.

scholarly journals IMMU-19. TARGETING GLIOBLASTOMA IMMUNOSUPPRESSION AND TREATMENT RESISTANCE WITH IBRUTINIB IN COMBINATION WITH STEREOTACTIC RADIATION AND IMMUNE CHECKPOINT BLOCKADE

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii108-ii108
Author(s):  
Jayeeta Ghose ◽  
Baisakhi Raychaudhuri ◽  
Kevin Liu ◽  
William Jiang ◽  
Pooja Gulati ◽  
...  
Keyword(s):  
T Cells ◽  
Combination Therapy ◽  
Median Survival ◽  
Immune Checkpoint ◽  
Survival Benefit ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Control Group ◽  
Triple Combination ◽  
Triple Combination Therapy

Abstract BACKGROUND Glioblastoma (GBM) is associated with systemic and intratumoral immunosuppression. Part of this immunosuppression is mediated by myeloid derived suppressor cells (MDSCs). Preclinical evidence shows that ibrutinib, a tyrosine kinase inhibitor FDA approved for use in chronic lymphocytic leukemia and known to be CNS penetrant, can decrease MDSC generation and function. Also, focal radiation therapy (RT) synergizes with anti-PD-1 therapy in mouse GBM models. Thus, we aimed to test the combination of these approaches on immune activation and survival in a preclinical immune-intact GBM mouse model. METHODS C57BL/6 mice intracranially implanted with the murine glioma cell line GL261-Luc2 were divided into 8 groups consisting of treatments with ibrutinib, RT (10 Gy SRS), or anti-PD-1 individually or in each combination (along with a no treatment control group). Immune cell subset changes (flow-cytometry) and animal survival (Kaplan-Meier) were assessed (n=10 mice per group). RESULTS Median survival of the following groups including control (28 days), ibrutinib (27 days), RT (30 days) or anti-PD-1 (32 days) showed no significant differences. However, a significant improvement in median survival was seen in mice given combinations of ibrutinib+RT (35 days), ibrutinib+anti-PD-1 (38 days), and triple therapy with ibrutinib+RT+anti-PD-1 (48 days, p &lt; 0.05) compared to controls or single treatment groups. The reproducible survival benefit of triple combination therapy was abrogated in the setting of CD4+ and CD8+ T cell depletion. Contralateral intracranial tumor re-challenge in long-term surviving mice suggested generation of tumor-specific immune memory responses. The immune profile of the tumor microenvironment (TME) showed increased cytotoxic CD8+ T cells and decreased MDSCs and regulatory T cells in the triple combination therapy mice compared to controls. CONCLUSION The combination of ibrutinib, focal RT, and anti-PD-1 immune checkpoint blockade led to a significant survival benefit compared to controls in a preclinical model of GBM.

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