Drug Des Dev Ther
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Mepolizumab is an anti-interleukin-5 (IL-5) humanized monoclonal antibody that has been recently approved as an add-on biological treatment for severe eosinophilic asthma, by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Moreover, mepolizumab is also currently included within the step 5 of the Global Initiative for Asthma guidelines, as an add-on therapy for severe uncontrolled asthma. The relevant therapeutic benefits detectable in patients with refractory eosinophilic asthma receiving mepolizumab depend on the pivotal pathogenic role played by IL-5 in these subjects. ⋯ Therefore, IL-5 represents a strategic molecular target for anti-eosinophilic treatments. By selectively inhibiting the biological actions of IL-5, mepolizumab provides a valuable therapeutic option for patients with severe eosinophilic asthma, refractory to standard treatments including inhaled and even systemic corticosteroids. In particular, the very important advantages linked to the use of mepolizumab in these difficult-to-treat asthmatic individuals have been well documented by several different trials performed worldwide.
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Pain localization is one of the hallmarks for the choice of first-line treatment in neuropathic pain. This literature review has been conducted to provide an overview of the current knowledge regarding the etiology and pathophysiology of localized neuropathic pain (LNP), its assessment and the existing topical pharmacological treatments. ⋯ Although there is a real need for more randomized controlled trials for both drugs, publications clearly demonstrate excellent risk/benefit ratios, safety, tolerance and continued efficacy throughout long-term treatment. A major advantage of both plasters is that they have proven efficacy and may reduce the risk of adverse events such as cognitive impairment, confusion, somnolence, dizziness and constipation that are often associated with systemic neuropathic pain treatment and reduce the quality of life. Topical modalities also may be used in combination with other drugs and analgesics with limited drug-drug interactions.
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Opioid use disorders (OUDs) have long been a global problem, but the prevalence rates have increased over 20 years to epidemic proportions in the US, with concomitant increases in morbidity and all-cause mortality, but especially opioid overdose. These increases are in part attributable to a several-fold expansion in the prescription of opioid pain medications over the same time period. ⋯ This article reviews the clinical trial data for novel buprenorphine delivery systems in the form of subcutaneous depot injections, transdermal patches, and subdermal implants for the treatment of OUD and discusses both the clinical efficacy of longer-acting formulations through increasing consistent medication exposure and their potential utility in reducing diversion. These new delivery systems also offer new dosing opportunities for buprenorphine and strategies for dosing intervals in the treatment of OUD.
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Eluxadoline is a novel drug approved for the management of diarrhea predominant irritable bowel syndrome (IBS-D). It has unique pharmacology and works on three different opioid receptors. ⋯ Clinical trial results and postmarketing reports show a risk of pancreatitis in patients without a gallbladder or those abusing alcohol. This review article will include information on clinical trial results related to IBS-D management as well as eluxadoline's limitations.
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Review
Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and place in therapy.
The identification of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer (NSCLC) has radically changed the treatment of a subset of patients harboring this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients. However, despite crizotinib's efficacy, patients almost invariably progress, with the central nervous system being one of the most common sites of relapse. ⋯ We provide an extensive overview of ceritinib from the design of the compound through preclinical data until efficacy and toxicity results from Phase I-III clinical studies. We review the molecular alterations associated with resistance to ceritinib and highlight the importance of obtaining tumor biopsy at progression to tailor therapy based upon the underlying resistance mechanism. We finally provide an outlook on novel rational therapeutic combinations.