Expedition 3 Trial

Achaia Taltoan, Mercer University College of Pharmacy

Alzheimer’s disease (AD) involves the development of extracellular amyloid beta (Aβ) plaques and intracellular fibrous tangles of tau protein. [1] The Aβ hypothesis postulates that overproduction or reduced clearance of Aβ from the cerebrum leads to formation of Aβ plaques, resulting in the cognitive deficits of Alzheimer’s disease. [1] Solanezumab is a humanized G1 monoclonal antibody that binds to Aβ peptides to increase clearance from the brain.[2] The Expedition and Expedition 2 trials evaluated the use of solanezumab in mild to moderate Alzheimer’s disease; pooled secondary analyses demonstrated a significant improvement in functional and cognitive decline in mild Alzheimer’s disease patients.[3] The Expedition 3 trial seeks to clarify the findings of the previous Expedition trials through limiting the population to mild Alzheimer’s disease patients.

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Vitamin D and Nifedipine in Preeclampsia

Achaia Taltoan, Mercer University College of Pharmacy

Preeclampsia is a syndrome characterized by a persistent blood pressure ≥ 140/90 mmHg and urine protein ≥ 300 mg/24 hours after 20 weeks of gestation. The American College of Obstetrics and Gynecology guidelines on pregnancy induced hypertension recommend immediate release nifedipine as one of the first line agents for treatment of blood pressure ≥ 160/110 mmHg. [1]

Although the pathogenesis of preeclampsia is unclear, some evidence suggests that vitamin D plays a role in the emergence of preeclampsia. [2] It is thought that vitamin D deficiency is associated with increased TNF-α and decreased IL-10 that are linked to hypertension during pregnancy and preterm birth. [2] The role of vitamin D as an antihypertensive agent for preeclampsia has not been assessed in human patients until this trial was conducted. [3]

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Erenumab for the Treatment of Episodic Migraine

Achal Patel, Mercer University College of Pharmacy

It is reported that migraines are the third most prevalent illness in the world, prominently affecting women. [1] Symptoms include visual disturbances, extreme sensitivity to sound, light, touch, and smell, and tingling or numbness in the extremities and face. [1] Migraines can be classified as either episodic (< 15 headache days/month) or chronic (≤ 15 headache days/month). [2

Erenumab is a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide (CGRP) receptor that is involved in migraine pathophysiology through nociceptive mechanisms in the trigeminovascular system. [3] In a prior phase two trial, erenumab has shown a reduction in the number of episodic migraines at monthly doses of 70 mg and 140 mg. [3]

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Searching for a New Indication

Tibin K. Titus, Mercer University College of Pharmacy

Hypertension is a worldwide problem with its prevalence increasing in the aging population. Complications of hypertension include stroke and cardiovascular diseases. [1] Angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), diuretics, and calcium channel blockers are recommended as first line therapy. [2]

Sacubitril/valsartan (Entresto®) is a combination product consisting of an angiotensin receptor neprilysin inhibitor, sacubitril, and an ARB, valsartan. [3] Previous studies with sacubitril/valsartan have demonstrated significant reductions in office and ambulatory BP compared with valsartan or placebo. [4]

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Novel Therapeutic Option Striking Multiple Downstream Inflammatory Pathways Associated with Uncontrollable Asthma

JoAnn Filipov, Mercer University College of Pharmacy

Despite established standard of care therapies, literature suggests that patients diagnosed with moderate-to-severe asthma experience frequent exacerbations and significant lung function limitations due to uncontrolled asthma. [1] A proposed molecular mechanism in asthma is the type 2 (T2) inflammatory pathway, characterized by elevated levels of blood eosinophils, serum IgE, and fractional exhaled nitric oxide (FENO). [2] Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine central for regulation of T2 immunity.  It has been identified as a potential therapeutic target for its ability to activate various cell types, such as basophils, mast cells, innate lymphoid cells, natural killer T cells, and neutrophils, across a broad patient population. [3]

Tezepelumab is an investigational human IgG2 monoclonal antibody. It binds to TSLP to prevent TSLP-receptor interaction. [4] This mechanism prevents the release of cytokines via immune cells targeted by TSLP early in the inflammation cascade. [5] It has been suggested that tezepelumab could be an adjunct therapy for patients with a history of asthma exacerbations and uncontrolled asthma who have failed previous therapies. [6]

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CRYSTAL Trial: Efficacy and Safety of Lesinurad and Febuxostat in Tophaceous Gout

Achaia Taltoan, Mercer University College of Pharmacy

Tophaceous gout is a form of advanced gout characterized by persistent arthritis, white-yellow intradermal deposits, and frequent recurrent acute attacks. The 2012 American Rheumatology Association and the European League Against Rheumatism (EULAR) guidelines for gout recommend xanthine oxidase inhibitors, allopurinol, or febuxostat as first line treatment for chronic tophaceous gout with a goal serum urate <6 mg/dL. [1,2] The EULAR and American Rheumatology Association guidelines suggest a goal serum urate < 5 mg/dL for patients with severe gout symptoms, including tophi, chronic arthropathy, and frequent attacks. [2] Evidence shows that approximately 40% of patients treated with allopurinol achieve serum urate levels less than 6 mg/dL, and about 48% of febuxostat patients can maintain target serum urate levels for three consecutive months. [3,4]

Lesinurad is a novel selective urate anion absorption inhibitor approved for combination with a xanthine oxidase inhibitor for gout patients whose serum urate targets are not achieved with xanthine oxidase inhibitor monotherapy. The CLEAR 1 and CLEAR 2 trial assessed the use of lesinurad with allopurinol in patients who failed to meet serum urate goals with monotherapy. [5,6] However, no trial assessed the combination of febuxostat and lesinurad in patients who failed xanthine oxidase monotherapy, until the CRYSTAL trial was conducted. [7]

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Reaching a New APEX; Betrixaban vs. Enoxaparin for Thromboprophylaxis

Achal Patel, Mercer University College of Pharmacy

Venous thromboembolism (VTE) is the third leading cause of vascular diagnosis following heart attack and stroke. [1] It is categorized into two types: deep vein thrombosis (DVT) and pulmonary embolism (PE). Venous thromboembolism affects men and women of all ages, and patients that are immobilized are at a higher risk. [1]

The Chest Guidelines recommend anticoagulants for up to two weeks after hospital discharge. [2] However, the risk of a VTE remains increased for at least a month. Therefore, Bevyxxa® (betrixaban), which is a direct and selective factor Xa inhibitor, was tested for extended-duration therapy for thromboprophylaxis in acutely ill medical patients. [3]

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