Expert review of respiratory medicine
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Expert Rev Respir Med · Jan 2019
ReviewBeclomethasone dipropionate, formoterol fumarate and glycopyrronium bromide as a combination therapy for chronic obstructive pulmonary disease.
The triple therapy term covers the combination of inhaled corticosteroid (ICS), long-acting β-receptor agonist (LABA) and long-acting anticholinergic drug (LAMA) in one or in separate inhalers. The latest GOLD 2018 (Global Initiative for Chronic Obstructive Disease) guidelines recommend the triple therapy in the management of chronic obstructive pulmonary disease (COPD) in patients of group D who despite the combination of two drugs: LAMA/LABA or ICS/LABA continue to have persistent symptoms or suffer from further frequent exacerbations. Areas covered: The first triple fixed-dose combination of extrafine beclomethasone/formoterol/glycopyrronium in one pMDI type inhaler intended for the treatment of COPD has been registered in Europe in 2017. ⋯ Expert commentary: A 20% reduction in the risk of moderate or severe exacerbation was found in patients receiving triple therapy compared to the ICS/LABA combination and LAMA monotherapy. Triple therapy reduces the number of exacerbations in comparison with double bronchodilatation (LABA/LAMA), thus representing an interesting therapeutic option in the management of COPD. The profile of side effects of triple therapy is typical for individual active agents included in the combination.
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Expert Rev Respir Med · Dec 2018
ReviewSolriamfetol for the treatment of daytime sleepiness in obstructive sleep apnea.
Introduction: Obstructive sleep apnea (OSA) is highly prevalent and constitutes a major health hazard. Current pharmacotherapy is ineffective in correcting sleep-disordered breathing and is used adjunctively to address residual sleepiness. A new drug, solriamfetol, a selective norepinephrine-dopamine reuptake inhibitor, is the first drug of its class that is being considered by the US Food and Drug Administration (FDA) to treat excessive sleepiness in OSA and narcolepsy patients. ⋯ Expert commentary: Solriamfetol shows promise as adjunctive therapy in OSA. It is well tolerated and effective in reducing sleepiness and is an alternative to modafinil or armodafinil. Unlike stimulants like methylphenidate or dextroamphetamine, it does not have cardiac effects, rebound hypersomnia, or withdrawal effects.
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Cystic fibrosis (CF) is the most common, life-limiting autosomal recessive disease in Caucasians, and is caused by defects in production of the CFTR ion channel. Until recently, there were no available treatments targeting the disease-causing defects in CFTR but newly developed CFTR modulators are changing the course of disease in CF. The newest modulator, tezacaftor, is a CFTR corrector that was recently approved by the FDA to be used in combination with the first approved CFTR potentiator, ivacaftor. ⋯ It is also approved for a large number of non-F508del, residual function mutations that are predicted to respond based on in vitro testing. The horizon for continued improvements in CFTR-targeted treatments is promising, with three-drug combinations currently in Phase 3 clinical trials, and other drugs with novel mechanisms of action being studied. Within the next 5 years, the vast majority of patients with CF are expected to have a modulator approved for their genotype.
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Expert Rev Respir Med · Sep 2018
ReviewAssessing effects of inhaled antibiotics in adults with non-cystic fibrosis bronchiectasis--experiences from recent clinical trials.
Non-cystic fibrosis bronchiectasis (NCFB) results from a permanent and progressive destruction of the airways leading to poor lung function. NCFB is characterized by recurrent lung infection, sputum production, and cough, often requiring long-term antibiotic therapy and hospitalization. At present, there are no approved therapies available. Clinical trials of inhaled antibiotics have shown promise against sputum bacterial load, but mixed results on clinical outcomes. Areas covered: The objective of this review is to provide an overview of NCFB and critically evaluate the evidence supporting the outcome measures used in recent clinical trials of inhaled antibiotics. These include quantitative changes in bacterial load, sputum purulence and yield, inflammatory markers, and lung function, as well as clinical changes in exacerbations, exacerbation frequency, hospitalizations, and health-related quality of life. Expert commentary: Recently completed large trials of inhaled antibiotics in NCFB did not consistently meet pre-specified end points, suggesting that we have not yet found the best enrollment criteria or outcome measures to evaluate efficacy, although reduced exacerbation frequency may be clinically most meaningful. Future trials may focus on specific patient populations at high risk with new information obtained through analyses of large international patient registries. ⋯ 6-MWT: Six-Minute Walk Test; AIR-BX: Aztreonam for Inhalation Solution in Patients with Non-Cystic Fibrosis Bronchiectasis trial; BSI: Bronchiectasis Severity Index; CAT: COPD Assessment Test; CF: Cystic Fibrosis; CFTR: Cystic Fibrosis Transmembrane Conductance Regulator; CFU: Colony-Forming Units; COPD: Chronic Obstructive Pulmonary Disease; CRP: C-Reactive Protein; DPI: Dry Powder for Inhalation; EMA: European Medicines Agency; ERS: European Respiratory Society; FACED: FEV1, Age, Chronic colonization by P. aeruginosa, Extension of bronchiectasis and Dyspnea; FDA: US Food and Drug Administration; FEV1: Forced Expiration in 1 s; FVC: Forced Vital Capacity; HFCC: High-Frequency Chest Compression; HRCT: High-Resolution Computed Tomography; HRQoL: Health-Related Quality of Life; LCQ: Leicester Cough Questionnaire; MID: Minimal Important Difference; NCFB: Non-Cystic Fibrosis Bronchiectasis; NTM: Nontuberculous Mycobacteria; ORBIT: Once-daily Respiratory Bronchiectasis Inhalation Treatment trial; PRO: Patient-Reported Outcomes; QoL-B: Quality of Life-Bronchiectasis; SGRQ: St. George's Respiratory Questionnaire; SWT: Shuttle Walk Test; TORCH: Towards a Revolution in COPD Health trial; UPLIFT: Understanding Potential Long-term Impacts on Function with Tiotropium trial.
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In non-small cell lung cancer (NSCLC), immunotherapy is one of today's most important and ground-breaking systemic treatments, mainly represented by antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death protein 1 or ligand 1 (PD-1/PD-L1). Durvalumab (MEDI4736) is a high-affinity human IgG1 monoclonal antibody that binds to PD-1 and CD80, blocking PD-L1, but not PD-L2. Areas covered: In advanced NSCLC patients, durvalumab has demonstrated activity and acceptable tolerability, particularly with ≥25% PD-L1 tumor expression in the EGFR and ALK wild-type population. ⋯ Expert commentary: Early data suggest promising activity for durvalumab with the CTLA-4 inhibitor tremelimumab, regardless of PD-L1 expression, and potentially in combination with other drugs such as platinum-doublet chemotherapy. However, treatment-related toxicity associated with the combinations is an important aspect of the benefit-risk evaluation in the decision-making process. Results of ongoing phase III trials will provide illuminating data to confirm the place of durvalumab in the management of NSCLC patients.