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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Adasuve for the Rapid Treatment of Agitation in Schizophrenia

JoAnn Filipov, Mercer University College of Pharmacy

Limited options of antipsychotic drug administration exist in the current standard of care for the acute treatment of agitation. [1] According to the Expert Consensus Guidelines for Treatment of Behavioral Emergencies, speed of onset is key in choosing medication administration route. [2] Since intravenous administration of antipsychotics necessitates established intravenous access, oral and intramuscular administrations are more prominently used. However, oral and intramuscular formulations have a more gradual onset of action, unlike intravenous pharmacokinetics, thus allowing for symptoms to escalate before they begin to resolve. [3] It is reported that patients with an episode of acute agitation often resist intramuscular administration, further escalating the risk of intensifying symptoms. Therefore, there is a need for anti-agitation medications with rapid onset of action and acceptable safety profile that are easy to administer. [4]

Loxapine, an antipsychotic indicated for the treatment of schizophrenia. [5] Loxapine is available as a capsule and intramuscular injection formulations, that have demonstrated efficacy in the treatment of agitation. [6] Due to the unmet need, a new formulation of loxapine, AdasuveÒ, was developed that can be inhaled via Staccato inhalation system. The system is shown to distribute loxapine with intravenous-like pharmacokinetics. [7] Below article summarized the efficacy and safety of Adasuve®. [8]

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A Novel drug, Ingrezza, for the Treatment of Tardive Dyskinesia

JoAnn Filipov, Mercer University College of Pharmacy

Tardive Dyskinesia is an involuntary movement disorder induced by continued exposure to dopamine receptor agents (DBRAs). It is associated with persistent, hindering physical conditions causing significant problems for psychiatric patients. [1] Second-generation (“atypical”) antipsychotics were thought have a decreased risk for tardive dyskinesia compared to first-generation antipsychotics, but current literature indicates the risk may be increased with both generations. [2] For management, the two main methods are: 1) reduce the antipsychotic dose or 2) discontinue the drug. However, literature suggests both may not be the best strategies as they may lead to suboptimal management of the psychiatric illness without resolving tardive dyskinesia. [3]

Vesicular monoamine transporter 2 (VMAT 2) inhibitors (e.g. tetrabenazine) have been used to treat movement-related symptoms of Huntington’s disease. [4] They regulate presynaptic packaging and dopamine release into the synapse. Due to this mechanism of action, it was proposed that VMAT2 inhibitors may be able to counterbalance involuntary movement side effects of antipsychotics. [5] Research sparked to develop valbenazine (Ingrezza Ò). Its exact mechanism of action is unknown; however, it is thought to reversibly inhibit VMAT2. [6] In 2017, the Food and Drug Administration approved valbenazine for the treatment of tardive dyskinesia in adults. Below summarizes the phase 3 trial of valbenazine. [7]

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Degludec Versus Glargine in Type 2 Diabetes for CV Risk

Tibin K. Titus, Mercer University College of Pharmacy

Type 2 diabetes affects millions of people worldwide. [1] Among the complications that arise from diabetes are cardiovascular (CV) complications such as stroke, coronary heart disease, and vascular disease. [1] Additionally, studies have shown that type 2 diabetics who require insulin have increased rates of cardiovascular events. [2,3]

Degludec is a new and ultra long acting basal insulin that came into the market in 2016. It is approved for glycemic control in type 2 diabetes. The Food and Drug Administration (FDA) requires all new diabetes drugs to have a CV risk study. [6] To fill the gap in knowledge for the CV safety of degludec, the following study was conducted. [7]

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Sotagliflozin Added to Insulin in Type 1 Diabetics

Shanterra Grable, Mercer University College of Pharmacy

Type 1 diabetes, previously considered juvenile diabetes, affects approximately 29 million adults worldwide. It develops when the pancreas stops producing insulin, eliminating the body’s ability to maintain glucose control. The autoimmune disease can have a rapid onset and must be managed with insulin administered via injection or by pump.  It is  approximated that less than one-third of people living with type 1 diabetes achieve the target A1c of less than 7%. [1]

Sotagliflozin is the newest agent in a class of antidiabetic agents known as sodium –glucose cotransporter 1 and 2 (SGLT2) inhibitors. Prior phase two studies on sotagliflozin have shown improved glycemic control, reduced body weight, and reduced glycemia in both type 1 and type 2 diabetics. None of the current medications on the market are approved for use in conjunction with insulin to lower glucose in type 1 diabetic patients. The inTandem3 phase three trial evaluated the effects of sotagliflozin when used in combination with insulin on glycemic control, instances of severe hypoglycemia, and diabetic ketoacidosis in adults with type 1 diabetes. [2]

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A Controlled Trial of Erenumab for Episodic Migraine

Shawn Yee, Mercer University College of Pharmacy

Migraine is a common neurological disorder that is ranked top 10 in terms of global disease burden. [1] The term migraine can be categorized into either episodic (< 15 migraine or headache days per month) or chronic (≥ 15 headache days per month, with ≥ eight days of migraine days). [2] Patients with debilitating or frequent migraines are eligible for preventative treatment; however, none of these options target the pathophysiologic pathways involved in migraines. [3]

Erenumab is a fully human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor, which is involved in migraine pathophysiology of the trigeminovascular system. [3] There are other monoclonal antibodies targeting CGRP, such as fremanezumb that have shown safety and efficacy in migraine prevention. Erenumab in particular, has also demonstrated efficacy in reducing the number of migraine days per month at doses ranging from 70 mg to 140 mg per month in a prior phase II trial. [3,4] Below is the summary of a phase III trial. [3]

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Delayed Versus Immediate Umbilical Cord Clamping

Shanterra Grable, Mercer University College of Pharmacy

Delayed umbilical cord clamping is performed from 25 seconds to five minutes after birth. The practice is thought to allow more blood to transfer from the placenta to the newborn, possibly increasing the baby’s blood volume by 30%. The American Congress of Obstetricians and Gynecologists (ACOG) supports delayed cord clamping in preterm infants but not in full term infants due to insufficient evidence showing benefits. The current standard during delivery  is to clamp the umbilical cord 10 to 30 seconds immediately after birth.  [1]

One of the associated benefits of delayed clamping is decreased risk of iron deficiency anemia due to transfer of additional 40 to 50 mg/kg of iron from the placenta to the infant. [1] Prior randomized controlled trials found that delayed cord clamping in preterm infants less than 32 weeks gestational age had lower instances of mortality, necrotizing enterocolitis, and infection than infants with immediate cord clamping; however, these studies did not show if delayed cord clamping is the sole factor leading to mortality and neurodevelopmental benefits. Despite the potential benefits, delayed clamping is not a universal practice due to concerns of delayed resuscitation and hyperbilirubinemia.  The following study was performed to add knowledge regarding the effects of delayed clamping on death and major morbidity in preterm infants. [2]

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