Clinical therapeutics
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Clinical therapeutics · Jun 2016
EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus.
During the last decade, the armamentarium for glucose-lowering drugs has increased enormously by the development of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors, allowing individualization of antidiabetic therapy for patients with type 2 diabetes (T2DM). Some combinations can now be used without an increased risk for severe hypoglycemia and weight gain. Following a request of the US Food and Drug Administration, many large cardiovascular (CV) outcome studies have been performed in patients with longstanding disease and established CV disease. ⋯ The recent IRIS (Insulin Resistance Intervention after Stroke) study documented a significant reduction in stroke and MI when pioglitazone instead of placebo was given to nondiabetic patients presenting with both stroke/transient ischemic attack and insulin resistance, confirming results from the PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events) study in patients with T2DM. Based on these new data, we suggest that the addition of both empagliflozin and pioglitazone to metformin might be the relative best option to reduce the high CV morbidity and mortality of patients with T2DM and already established CV complications. The very recent announcement that the CV outcome study with liraglutide (LEADER) also demonstrated a significant reduction of the composite endpoint (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) gives new hope for further beneficial treatment options for T2DM patients with established CVD.
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Clinical therapeutics · Jun 2016
Randomized Controlled TrialRescue Sedation With Intranasal Dexmedetomidine for Pediatric Ophthalmic Examination After Chloral Hydrate Failure: A Randomized, Controlled Trial.
It is a challenge to rescue ophthalmology examinations performed in children in the sedation room after initial chloral hydrate failure. Intranasal dexmedetomidine can be used in rescue sedation in children undergoing computed tomography. The present study aimed to assess the efficacy and tolerability of intranasal dexmedetomidine use in children undergoing ophthalmic examination after chloral hydrate failure. ⋯ In children undergoing ophthalmic examination, intranasal dexmedetomidine can be administered in the sedation room for rescue sedation after chloral hydrate failure, with the 2-μg/kg dose being more efficacious than the 1-μg/kg dose, as measured by success rate. ClinicalTrials.gov identifier: NCT02077712.
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Clinical therapeutics · Jun 2016
Randomized Controlled Trial Multicenter StudyEfficacy, Safety, and Tolerability of Fulranumab as an Adjunctive Therapy in Patients With Inadequately Controlled, Moderate-to-Severe Chronic Low Back Pain: A Randomized, Double-blind, Placebo-controlled, Dose-ranging, Dose-loading Phase II Study.
Fulranumab is an investigational, fully human recombinant monoclonal antibody (IgG2) that neutralizes the biological actions of human nerve growth factor. Low back pain is a common cause of noncancer chronic pain and represents one of the most significant socioeconomic health-related problems in developed countries. This randomized, double-blind, placebo-controlled study was conducted to evaluate the analgesic effect of fulranumab in patients with moderate-to-severe chronic low back pain. ⋯ Fulranumab did not demonstrate efficacy compared with placebo in patients with chronic low back pain but was generally well-tolerated. ClinicalTrials.gov identifier: NCT00973024.
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Clinical therapeutics · Jun 2016
Randomized Controlled TrialLorcaserin in Obese and Overweight Patients Taking Prohibited Serotonergic Agents: A Retrospective Analysis.
Lorcaserin is a selective serotonin 2C receptor (5-HT2C) agonist approved in the United States for use in chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. Its pharmacologic activity is limited to 5-HT subtype 2 receptors. The potency of lorcaserin for the 5-HT2C receptor is 14-fold greater than its potency for the 5-HT2A receptor and 61-fold greater than its potency for the 5-HT2B receptor. Although 5-HT receptors have been implicated in serotonin syndrome, the precise pathogenesis is unknown. Given a theoretic risk for this syndrome in patients administered lorcaserin either alone or in combination with certain serotonergic agents (eg, selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), patients taking prohibited serotonergic agents were excluded from the Phase III clinical trials. This retrospective analysis evaluated the tolerability of lorcaserin in patients who took protocol-allowed or proscribed serotonergic agents for varying durations of up to 1 year during the BLOOM, BLOSSOM, and BLOOM-DM studies. ⋯ The concurrent use of lorcaserin and prohibited or allowed serotonergic agents did not appear to have increased the spectrum or intensity of AEs potentially associated with serotonin excess in this limited dataset. However, the sample population was too small to rule out an effect on a rare event such as serotonin syndrome. ClinicalTrials.gov identifiers: NCT00395135, NCT00603902, and NCT00603291.
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Clinical therapeutics · Jun 2016
Treatment Patterns, Direct Cost of Biologics, and Direct Medical Costs for Rheumatoid Arthritis Patients: A Real-world Analysis of Nationwide Japanese Claims Data.
The aims of this article were to characterize the patterns of treating rheumatoid arthritis with biologics and to evaluate costs using claims data from the Japan Medical Data Center Co, Ltd. ⋯ Considered costs and discontinuation and switching event rates were lowest with ETN versus IFX, ADA, or TCZ used as the first-line biologic. Despite limitations, these findings imply clinical cost-reductive benefits of ETN as the first-line biologic treatment option for rheumatoid arthritis in Japan.