Drugs

Manka, Paul; Zeller, Amos; Syn, Wing-Kin

doi: 10.1007/s40265-019-01126-9pmid: 31119644

Fibrosis is a common outcome of most chronic inflammatory diseases, characterized by the accumulation of excessive extracellular matrix components. Individuals with progressive liver fibrosis develop cirrhosis, are at risk of developing liver cancer, and may succumb to liver failure. Although a number of specific therapies for different diseases have been developed and successfully used, for example, direct antiviral agents in treatment for hepatitis C, effective and specific antifibrotic therapies are still not available. Liver biopsy remains the gold standard of staging liver fibrosis. However, transient elastography is increasingly being used in clinical trials and in hepatology clinics as part of standard-of-care evaluation because it is easy to use. Magnetic resonance (MR)-elastography is most accurate in evaluating fibrosis stage but is costly and time consuming and thus not readily available. Recent advances, however, have been made in areas of diagnostic and therapeutic modalities, with an increasing number of potential drugs currently in phase II and III trials, particularly in the field of non-alcoholic steatohepatitis-related liver fibrosis. These new drugs target multiple pathways involved in the pathogenesis of chronic liver disease, and we anticipate that some of them may soon be approved for use in patients.

Sarris, Jerome

doi: 10.1007/s40265-019-01134-9pmid: 31114975

The field of ‘nutritional psychiatry’ has evolved with rapidity over the past several years, with an increasing amount of dietary or nutrient-based (nutraceutical) intervention studies being initiated, and more preclinical and epidemiological data being available. This emergent paradigm involves the clinical consideration (where appropriate) of prescriptive dietary modification/improvement, and/or the select judicious use of nutrient-based supplementation to prevent or manage psychiatric disorders. In the last several years, significant links have increasingly been established between dietary quality and mental health (although not all data are supportive). Maternal and early-life nutrition may also affect the mental health outcomes in offspring. In respect to nutraceutical research, like with many recent conventional drug studies, results are fairly mixed across the board, and in many cases there is not emphatic evidence to support the use of nutraceuticals in various psychiatric disorders. This may in part be due to a preponderance of recent studies within the field revealing marked placebo effects. Due to current indicators pointing towards mental disorders having an increasing burden of disease, bold and innovative approaches on a societal level are now required. In light of the widespread use of nutrient supplements by those with and without mental disorders, it is also critical that scientifically rigorous methodologies be brought to bear on the assessment of the efficacy of these supplements, and to determine if, or what dose of, a nutrient supplement is required, for whom, and when, and under what circumstances. More simple studies of additional isolated nutrients are not of great benefit to the field (unless studied in supra-dosage in an individualised, biomarker-guided manner), nor, based on recent data, is the research of ‘shotgun’ formulations of nutraceuticals. The next critical step for the field is to design psychiatric interventional studies for both dietary modification and nutraceuticals, based on more of a personalised medicine approach, using biomarkers (e.g. nutrient deficiencies, inflammatory cytokine levels, genomic assessment, microbiome analysis) and a person’s dietary patterns and individual macro/micronutrient requirements.

Blanton, Henry; Brelsfoard, Jennifer; DeTurk, Nathan; Pruitt, Kevin; Narasimhan, Madhusudhanan; Morgan, Daniel; Guindon, Josée

doi: 10.1007/s40265-019-01132-xpmid: 31127530

Increases in cancer diagnosis have tremendous negative impacts on patients and their families, and major societal and economic costs. The beneficial effect of chemotherapeutic agents on tumor suppression comes with major unwanted side effects such as weight and hair loss, nausea and vomiting, and neuropathic pain. Chemotherapy-induced peripheral neuropathy (CIPN), which can include both painful and non-painful symptoms, can persist 6 months or longer after the patient’s last chemotherapeutic treatment. These peripheral sensory and motor deficits are poorly treated by our current analgesics with limited effectiveness. Therefore, the development of novel treatment strategies is an important preclinical research focus and an urgent need for patients. Approaches to prevent CIPN have yielded disappointing results since these compounds may interfere with the anti-tumor properties of chemotherapeutic agents. Nevertheless, the first (serotonin noradrenaline reuptake inhibitors [SNRIs], anticonvulsants, tricyclic antidepressants) and second (5% lidocaine patches, 8% capsaicin patches and weak opioids such as tramadol) lines of treatment for CIPN have shown some efficacy. The clinical challenge of CIPN management in cancer patients and the need to target novel therapies with long-term efficacy in alleviating CIPN are an ongoing focus of research. The endogenous cannabinoid system has shown great promise and efficacy in alleviating CIPN in preclinical and clinical studies. In this review, we will discuss the mechanisms through which the platinum, taxane, and vinca alkaloid classes of chemotherapeutics may produce CIPN and the potential therapeutic effect of drugs targeting the endocannabinoid system in preclinical and clinical studies, in addition to cannabinoid compounds diffuse mechanisms of action in alleviation of CIPN.

Blair, Hannah

doi: 10.1007/s40265-019-01133-wpmid: 31119643

Tiotropium/olodaterol (Stiolto® Respimat®; Spiolto® Respimat®) is an inhaled fixed-dose combination of the long-acting muscarinic antagonist tiotropium bromide (hereafter referred to as tiotropium) and the long-acting β2-adrenergic agonist olodaterol. It is available in several countries, including the USA, Japan, China and those of the EU, where it is indicated for the long-term maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). The efficacy of tiotropium/olodaterol 5/5 μg/day in patients with COPD was evaluated in phase III or IV trials of 6–52 weeks’ duration. Tiotropium/olodaterol improved lung function to a greater extent than each of its individual components or placebo in 12- and 52-week trials. In 6-week trials, tiotropium/olodaterol provided greater lung function benefits over 24 h than the individual components, placebo or twice-daily fluticasone propionate/salmeterol. Tiotropium/olodaterol also demonstrated beneficial effects on health-related quality of life (HR-QoL), dyspnoea, inspiratory capacity, exercise endurance and the need for rescue medication. In an 8-week open-label trial, umeclidinium/vilanterol was superior to tiotropium/olodaterol for the primary endpoint of trough forced expiratory volume in 1 s. The tolerability profile of tiotropium/olodaterol was generally similar to that of the individual components. In conclusion, tiotropium/olodaterol provides a useful option for the maintenance treatment of COPD, with the convenience of once-daily administration via a single inhaler.

Al-Salama, Zaina T.

doi: 10.1007/s40265-019-01140-xpmid: 31144287

Abstract Siponimod (Mayzent®) is an oral selective sphingosine 1-phosphate receptor subtypes 1 and 5 (S1PR1,5) modulator being developed by Novartis Pharmaceuticals for the treatment of multiple sclerosis (MS) and intracerebral haemorrhage. In March 2019, siponimod received its first global approval in the USA, for the treatment of adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. Siponimod is under regulatory review in the EU and Japan for secondary progressive MS. This article summarizes the milestone in the development of siponimod leading to this first global approval for MS in the USA.