Therapeutic advances in respiratory disease
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Ther Adv Respir Dis · Aug 2015
ReviewEmerging therapies for the prevention of acute respiratory distress syndrome.
The development of acute respiratory distress syndrome (ARDS) carries significant risk of morbidity and mortality. To date, pharmacological therapy has been largely ineffective for patients with ARDS. We present our personal review aimed at outlining current and future directions for the pharmacological prevention of ARDS. ⋯ Due to potential for systemic adverse effects to neutralize any pharmacological benefits of systemic therapy, inhaled medications appear particularly attractive candidates for ARDS prevention. This is because of their direct delivery to the site of proposed action (lungs), while the pulmonary epithelial surface is still functional. We postulate that overall morbidity and mortality rates from ARDS in the future will be contingent upon decreasing the overall incidence of ARDS through effective identification of those at risk and early application of proven supportive care and pharmacological interventions.
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Ther Adv Respir Dis · Aug 2015
ReviewEvidence for the efficacy and safety of anti-interleukin-5 treatment in the management of refractory eosinophilic asthma.
Two recent phase III trials in patients with severe eosinophilic asthma have shown that anti-interleukin 5 (IL-5) therapy with mepolizumab reduces the frequency of asthma attacks, improves symptoms and allows patients to reduce oral glucocorticoid use without loss of control of asthma. An earlier large 616 patient Dose Ranging Efficacy And safety with Mepolizumab in severe asthma (DREAM) study had shown that the only variables associated with treatment efficacy were a prior history of asthma attacks and the peripheral blood eosinophil count. The link between blood eosinophil counts and treatment efficacy is biologically obvious given that IL-5 has a pivotal role in eosinophil production, proliferation and chemotaxis. ⋯ In addition, benralizumab, an IL-5α receptor blocker, has shown good effects in a phase IIb RCT with patients with severe asthma that had sputum eosinophilia and more recently in a phase IIa trial with patients with eosinophilic chronic obstructive pulmonary disease. Therefore anti-IL-5 treatment seems generally effective in eosinophilic asthma, either assessed by blood or airway eosinophilia. This factor together with the impressive clinical efficacy and good safety profile make anti-IL-5 (mepolizumab, reslizumab) and benralizumab (anti-IL-5 receptor α) very promising drugs for the treatment of patients with severe eosinophilic asthma, a subgroup that is in desperate need of better treatments.
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Ther Adv Respir Dis · Aug 2015
ReviewNintedanib in non-small cell lung cancer: from preclinical to approval.
Angiogenesis is a driving force of a tumor's development. Targeting this process is an attractive option, as this is a feature shared by most of the solid tumors. A lot of antiangiogenic drugs have been developed following this path, including bevacizumab, sorafenib, sunitinib, vandetanib, ramucirumab, motesanib and many others. ⋯ A phase III clinical trial that recently concluded provided us with relevant information in patients with NSCLC of adenocarcinoma histology. Here we present a short overview of the tumor angiogenesis pathways and antiangiogenic drugs. In particular, we will focus on nintedanib, from the preclinical studies to the latest phase III clinical trial that allowed this new agent to be approved by the European Medicines Agency as a second-line treatment option in association with docetaxel for NSCLC patients with adenocarcinoma histology.
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Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease that occurs in older adults. The clinical course of IPF is variable and hard to predict in an individual patient. Nintedanib is a tyrosine kinase inhibitor that has recently been approved in the US and European Union for the treatment of IPF. ⋯ The safety and efficacy of nintedanib have been investigated in the phase II TOMORROW trial and in two replicate 52-week randomized, placebo-controlled phase III trials known as the INPULSIS trials. These trials demonstrated that nintedanib slowed disease progression by reducing the annual rate of decline in forced vital capacity, with a manageable side-effect profile. In this review, we summarize key data supporting nintedanib as a treatment for patients with IPF and address key questions regarding the use of nintedanib in the clinical setting.