Expert opinion on pharmacotherapy
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Expert Opin Pharmacother · Sep 2016
ReviewObeticholic acid for the treatment of primary biliary cholangitis.
Primary biliary cholangitis (PBC) is an autoimmune disease of the liver characterized by destruction and inflammation of the intrahepatic bile ducts. The disease affects mainly women. The disease is often discovered through abnormal alkaline phosphatase (ALP) activity, and is confirmed when anti-mitochondrial antibodies (AMA) are present. The etiology of PBC is poorly understood. Cigarette smoking, immune dysregulation, nail polish, urinary tract infections, and low socioeconomic status have been implicated but none have been confirmed. Genome wide association studies (GWAS) have disclosed strong associations between certain human leukocyte antigen (HLA) alleles and PBC. PBC can progress to cirrhosis and end-stage liver disease. Hepatocellular carcinoma (HCC) develops in up to 3.5% of PBC patients. Ursodeoxycholic acid (UDCA) is the only medication approved for the treatment of PBC. The use of UDCA in PBC delays histological progression and extends the transplant-free survival. 40% of PBC patients do not respond adequately to UDCA, and these patients are at high risk for serious complications. Therefore, there is a critical need for more effective therapies for this problematic disease. Multiple other agents have either been or are currently being studied as therapeutic options in UDCA non-responder PBC patients. Six-ethyl chenodeoxycholic acid (6-ECDCA), a potent farnesoid X receptor (FXR) agonist, has shown anti-cholestatic activity in rodent models of cholestasis. Obeticholic acid (OCA, 6-ECDCA, or INT-747), a first-in-class FXR agonist, has been examined in PBC patients with inadequate response to UDCA, and shown promising results. Particularly, initial clinical trials have demonstrated that the use of OCA (in addition to UDCA) in PBC patients with inadequate response to UDCA led to significant reduction of serum alkaline phosphatase (ALP, an important prognostic marker in PBC). More recently, the results of a randomized clinical trial of OCA monotherapy in PBC reported significant reduction of ALP in the treatment group compared to placebo. ⋯ If approved by the U.S. FDA, OCA will likely be an important alternative add-on therapy in PBC patients who have inadequate response to UDCA.
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Expert Opin Pharmacother · Sep 2016
ReviewSelexipag for the treatment of pulmonary arterial hypertension.
Targeted pulmonary vasoactive substances are the cornerstone of treatment in pulmonary arterial hypertension (PAH). Approved drugs act on various receptors and molecules within the pulmonary arteries, mainly causing pulmonary vasodilation and potentially reversing remodeling with consequent improvement of right ventricular function. A key role is attributed to the prostacyclin pathway and especially the prostacyclin receptor (IP). Selexipag is a recently developed, non-prostanoid, oral IP receptor agonist for the treatment of PAH which has been approved in countries/regions including the USA and Europe. ⋯ Oral selexipag offers a promising therapeutic option within the class of available drugs targeting IP receptors. However, its role as first-line therapy based on its efficacy/side-effect profile in current studies is questionable. Most likely, selexipag will be used in combination with other PAH-specific oral drugs. The potential of selexipag to replace or postpone the use of inhaled or parenteral prostanoids needs to be investigated in future trials.
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Expert Opin Pharmacother · Sep 2016
Randomized Controlled Trial Comparative StudyEvaluation of the antihyperalgesic effect of tapentadol in two human evoked pain models - the TapCapMentho pilot trial.
Tapentadol is effective in the treatment of neuropathic and nociceptive pain and in acute and chronic pain conditions; two mechanisms combining opioid µ-receptor agonism and noradrenergic reuptake inhibition underlie its analgesic effect. ⋯ The discrepancy between pain models using healthy volunteers and drug trials under real acute and chronic pain conditions in patients as well as methodological aspects may have contributed to this result. The impact of these findings questions the general use of pain models as predictors for early decision making during drug development. The study was registered in ClinicalTrials.gov (NCT01615510).
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Expert Opin Pharmacother · Aug 2016
Randomized Controlled TrialEvaluation of rotigotine transdermal patch for the treatment of depressive symptoms in patients with Parkinson's disease.
To evaluate the dopamine receptor agonist, rotigotine, for improving depressive symptoms in patients with Parkinson's disease (PD). ⋯ No statistically significant improvement in depressive symptoms were observed with rotigotine versus placebo. ADL, motor function, and patient-rated apathy improved numerically. ClinicalTrials.gov: NCT01523301.
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Expert Opin Pharmacother · Jul 2016
ReviewRecent advances in pharmacological treatments of hyperkalemia: focus on patiromer.
Hyperkalemia is a common electrolyte disorder, especially among patients with chronic kidney disease (CKD), diabetes mellitus, or heart failure, and is associated with a significantly increased risk for all-cause mortality. Hyperkalemia remains a vexing and challenging problem for clinicians, particularly in the management of patients with chronic kidney disease and congestive heart failure. Several observational and retrospective studies have reported a large gap between recommendations in guidelines and real-world practice in the implementation of RAASi therapies. RAASi treatment regimens are frequently down-titrated or discontinued following hyperkalemia events, with consequent worse outcomes than patients who remain on maximum doses. ⋯ Recently, patiromer was approved by the FDA as the first new potassium binder for the treatment of hyperkalemia in over 50 years. Based on the results of phase II and phase III studies, we conclude that patiromer is a well-tolerated and predictable medication to consistently and safely reduce serum potassium levels and to sustain normokalemia for periods up to 52 weeks in patients with diverse underlying diseases including congestive heart failure, and chronic kidney disease. Future research questions that should be evaluated are: the role of patiromer in treating hyperkalemia and the potential to thereby allow the optimal management of resistant hypertension and the use of high dose MRAs in patients with acute decompensated heart failure. Additional research is also warranted in the potential safety benefits of reducing potassium fluctuations in patients on hemodialysis as a result of treatment of hyperkalemia with patiromer.