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News Capsules - May 2025

Long-Term Effects of Atorvastatin in Cardiovascular Disease

The Anglo-Scandinavian Cardiac Outcomes Trial investigated the long-term effects of atorvastatin, a cholesterol-lowering drug, on cardiovascular (CV) disease in hypertensive individuals with additional risk factors. The lipid-lowering arm of the trial randomized over 10,000 participants with total cholesterol <6.5 mmol/L to receive either atorvastatin 10 mg or a placebo for an average of 3.3 years. The initial results showed that atorvastatin significantly reduced the incidence of major CV events like myocardial infarction (MI) and stroke.

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Brexpiprazole for Adolescents with Schizophrenia

A randomized, double-blind, placebo-controlled phase 3 trial evaluated the efficacy and safety of brexpiprazole in adolescents (ages 13 to 17) with schizophrenia. Participants in the trial had a confirmed diagnosis of schizophrenia, a history of illness for at least 6 months, a need for antipsychotic medication, and a score of 80 or greater on the Positive and Negative Syndrome Scale (PANSS).

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Cenobamate in Drug-Resistant Epilepsy

A retrospective, multicenter study analyzed the real-world effectiveness and tolerability of cenobamate as adjunctive therapy for adults with drug-resistant focal-onset seizures participating in Early Access Programs. The study included 298 patients with a long history of epilepsy (median 22 years) and a high number of previously failed antiseizure medications, with 41.9% having undergone epilepsy surgery. The primary efficacy endpoint was a 50% or greater reduction in seizure frequency after 3 months of maintenance therapy.

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Inebilizumab in Generalized Myasthenia Gravis

Autoimmune myasthenia gravis is characterized by autoreactive B cells producing autoantibodies that disrupt neuromuscular transmission, leading to fluctuating muscle weakness. Current treatments include glucocorticoids, cholinesterase inhibitors, thymectomy, and immunosuppressants, which aim to reduce mortality and alleviate symptoms; however, limitations in efficacy, side effects, and poor response in some patients highlight the need for alternative therapies.

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Drug News Abstracts Archive

Drug News Abstracts - May 2022
Differences in Response to Antidepressants in Combination with Mood Stabilizers and Antipsychotics for Unipolar and Bipolar DepressionA study published in the Journal of Clinical Psychopharmacology is the first to explore clinical response rates to antidepressants in combination augmentation strategies with either antipsychotics or mood stabilizers and to illuminate the differences between response to similar pharmacotherapies in patients with unipolar and bipolar depression. Antidepressant prescriptions in bipolar disorder have surged in the past two decades, from 17.9% to 40.9% of patients, mostly based on the success of newer antidepressants in treating unipolar depression. They remain the leading treatment prescribed for bipolar disorder, despite inconsistent evidence for efficacy and the occurrence of adverse events, such as treatment-emergent affective switch (TEAS).READ MORE...The study relied on data from a research database for patients followed at the McGill University Health Center’s Mood Disorders Clinic for 2 or more years (mean, 7.5 years). It included 206 patients; 76 met the criteria for treatment-resistant depression (TRD), failing two or more trials with different antidepressants in either monotherapy or combination therapy for 3 or more weeks. The remaining 130 patients met criteria for bipolar disorder, all of whom had failed to respond to one or more trials with a mood stabilizer plus an antipsychotic. Clinical outcomes were determined by comparing changes on these behavioral scales between start of a treatment regimen and after 3 months of an unchanged regimen; scales were the 17-item Hamilton Depression Rating Scale (HAMD-17), Quick Inventory of Depressive Symptomatology (QIDS-C16), and Clinical Global Impression–Severity of Illness (CGI-S). Response was defined as 50% or greater reduction from the pretreatment HAMD-17 score, and remission was defined as a score of less than 7 on the HAMD-17 at the end point.At baseline, the TRD group had, on average, moderate to severe depression (HAMD-17: 23.86), with scores on QIDS-C16 of 15.0 and on CGI-S of 5.2. The bipolar group had, on average, mild to moderate depression (HAMD-17, 18.3), with scores on QIDS-C16 of 12.3 and on CGI-S of 4.5. Clinical improvements in depression severity were seen with the different treatment strategies:· Antidepressants plus antipsychotics produced significantly greater improvement on HAMD-17 for the TRD group (score, 9.2) vs. bipolar group (score, 5.1), but no significant differences on other scales: 5.6 vs. 4.5 on QIDS-C16 and 1.7 vs. 1.4 on CGI-S.· Antidepressants plus mood stabilizers showed marginally greater improvement on HAMD-17 for the TRD group (score, 8.8) vs. the bipolar group (score, 6.3); the combination of antidepressants, antipsychotics, plus mood stabilizers also showed marginally significant differences between the TRD group (score, 9.3) and the bipolar group (score, 6.9) on the HAMD-17. But other clinical scales failed to reveal significant differences in outcomes.Response and remission rates did not differ significantly between the two types of depression, nor did they differ based on any type of combination treatment. Response rates were 26% in the TRD group and 19% in the bipolar group for all treatment strategies; remission occurred in 5% of the TRD group and in 7% of the bipolar group. These low rates of remission reflect the refractory nature of depression in these patients.These data, seen in a natural clinical setting, highlight the importance of augmentation strategies in depression. The study also showed that the reduction of depressive symptoms was greater in the TRD group compared with the bipolar group when pharmacologic combinations included an antidepressant and that adding an antidepressant to the treatment regimen for bipolar depression increased the risk of TEAS, cycle acceleration, and mood destabilization in these patients. Taken together, these results raise questions about the use of antidepressants in bipolar disorder. (Moderie, C., et al. (2022). Distinct effects of antidepressants in association with mood stabilizers and/or antipsychotics in unipolar and bipolar depression. J Clin Psychopharmacol, 42(2), 118–124. Retrieved May 2022 from https://journals.lww.com/psychopharmacology/Fulltext/2022/03000/Distinct_Effects_of_Antidepressants_in_Association.2.aspx)Released: May 2022Nursing Drug Handbook© 2022 Wolters KluwerAtogepant and Sumatriptan Safe to Administer Together for MigraineAcute treatment for migraine attacks includes triptans; the most commonly used triptan is sumatriptan. Preventive therapies are also beneficial; they may be used in those with severe or frequent migraine attacks and in those with a poor response to acute treatments. Atogepant, a calcitonin gene-related peptide (CGRP) receptor antagonist, has been approved as a preventive treatment for migraine; it can be expected, therefore, that it could possibly be given in combination with sumatriptan.READ MORE...An open-label, randomized, 3-way crossover study evaluated the possibility of how administering the two drugs together affected pharmacokinetic parameters, and compared how the body absorbed, distributed, and eliminated the two drugs when given together compared to each drug given alone. The trial enrolled 30 healthy adults, of whom 27 completed the study; 29 received a single oral 100-mg dose of sumatriptan, 28 received a single oral 60-mg atogepant dose, and 27 received the drugs administered together. Blood samples were drawn to determine plasma drug concentrations on days 1, 8, and 15, and safety and tolerability were monitored by physical exams, vital signs, clinical lab tests, and ECGs.Most of the pharmacokinetic parameters were only minimally changed when atogepant was given with sumatriptan, compared to either drug given alone. The peak plasma concentration (Cmax) of atogepant was reduced by 22% when administered with sumatriptan. Coadministration delayed the median atogepant Tmax (time to maximum plasma drug concentration) by 1.5 hours. This lower Cmax and delayed Tmax could be attributed to the effect of sumatriptan on gastric emptying. However, these changes are expected to have minimal clinical relevance because use with sumatriptan was not shown to not affect the overall systemic exposure to atogepant.These results allay concerns about the safety and tolerability of using these two antimigraine medications together, leading to more options for treating severe or frequent migraines. Further studies are needed to confirm these findings. (Boinpally, R., et al. (2021). Atogepant and sumatriptan: No clinically relevant drug-drug interactions in a randomized, open-label, crossover trial. Pain Management; 12(4), 499–508. Retrieved May 2022 from https://www.futuremedicine.com/doi/10.2217/pmt-2021-0073)Released: May 2022Nursing Drug Handbook© 2022 Wolters KluwerRisk of Anaphylaxis after Second Dose of COVID Vaccine is Low in Those Who Had Such a Reaction to First DoseOne barrier to successful vaccination is the occurrence of rare adverse reactions to the vaccines, including severe allergic reactions, which occur in 7.9 per 1 million vaccinations. As the rollout for the SARS-CoV2 mRNA vaccines was underway, allergic reactions rapidly led to recommendations that people with an immediate allergic reaction to the first dose shouldn’t receive additional doses. But this places those people at risk of contracting the disease.READ MORE...A review article published in JAMA Internal Medicine examined 22 studies and asked the question: What is the risk of an immediate severe allergic reaction (anaphylaxis) to a second dose of a SARS-CoV2 mRNA vaccine among individuals who had an immediate allergic reaction of any severity to their first dose? The researchers examined studies conducted from the onset of COVID-19 vaccination through October 4, 2021; immediate allergic reaction was defined as one that occurred within 4 hours of the first dose. The individuals received the second vaccine under the supervision of an allergist.The meta-analysis identified 1,366 individuals who had immediate allergic reactions to their first vaccination, among them, 78 persons who had suffered an anaphylactic reaction to the first dose. Of the 1,366 individuals, pooled analysis showed that 6 experienced severe immediate allergic reaction (absolute risk, 0.16%) and 232 developed mild immediate symptoms (absolute risk, 13.65%) to the second dose of the vaccine. Of the 78 persons who had suffered anaphylaxis after the first dose, 4 had a second severe allergic immediate reaction (absolute risk, 4.94%) and 15 had mild immediate symptoms (absolute risk, 9.54%). None of the 6 persons who experienced severe allergic reactions to the second dose died; 5 recovered after receiving IM epinephrine and the sixth recovered without treatment. Subgroup analysis, examining studies that permitted altered dosing, premedication before vaccination, or skin testing, didn’t result in alterations to these findings.These findings contradict the common assumption that a history of allergic reactions guarantees another to subsequent vaccine exposure. In such individuals, consultation with an allergist before the second vaccination is recommended. (Chu, D. K., et al. (2022). Risk of second allergic reaction to SARS-CoV-2 vaccines: A systematic review and meta-analysis. JAMA Intern Med, 182(4), 376–385. Retrieved May 2022 from https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2788991)Released: May 2022Nursing Drug Handbook© 2022 Wolters KluwerFDA Considering Changes to Improve Safe Disposal of Unused Prescription Opioid AnalgesicsThe FDA is seeking public comments until June 21, 2022, to a potential change to the Opioid Analgesic Risk Evaluation and Mitigation Strategy that would require that opioid analgesics used in outpatient settings be dispensed with prepaid mail-back envelopes and that pharmacists provide patient education on safe disposal of unused opioids. They seek comments from interested parties: patients, patient advocates, health care professionals, academics, researchers, pharmaceutical industry, and other government entities.READ MORE...The FDA’s efforts to address the opioid crisis include a focus on encouraging appropriate disposal of unused opioids. Current recommendations for disposal of unused drugs include permanent collection sites, such as kiosks in pharmacies or at community take-back events. If such opportunities aren’t available, the FDA recommends flushing those opioids on the Flush List (safe to be disposed in that way) or mixing with an unpalatable substance and disposing in the household trash. All these methods have their drawbacks, from environmental concerns to worries about safety to concerns about cost and inconvenience. Data show that educating patients about disposal options increases the disposal rate of unused medications; it’s hoped that providing an easy, cost-free option along with education will further increase that rate.Patients commonly report having unused opioid analgesics after surgical procedures; studies show a range of 67% to 92% of patients, depending on the surgery, report excess opioid analgesics. Opioids used for chronic pain can also result in excess pills requiring disposal, due to changes in dose or medication, discontinuation of opioid treatment, or death of the patient. These unused opioids then end up sitting in their house, creating opportunities for nonmedical use, accidental exposure, overdose, and new cases of opioid addiction. Despite the risks associated with having unused opioid analgesics in the home, most studies found that fewer than 50% of patients report disposing of them. Patient education on the need to dispose of them has been shown to increase disposal rates; in one study that examined the effect of providing patient education, a take-home disposal method, or both, use of either intervention increased the disposal rate by about 12% and the combined intervention increased the disposal rate by 19.5%. It is reasonable to assume that mail-back envelopes are one such method that could increase this disposal rate.The FDA is anticipating that this REMS-mandated disposal program could complement programs already in place. Recognizing that dispensing mail-back envelopes with every opioid prescription would be inefficient, the FDA proposes the use of algorithms that could enable pharmacists to target those prescriptions most likely to result in unused medications (that is, when filling new prescriptions for acute pain treatment or when changing the dose, medication, or formulation in a recurring prescription). (U.S. Food & Drug Administration. News Release. (2022). FDA considers new approach to improve safe disposal of prescription opioid analgesics, decrease unnecessary exposure to unused medication. Retrieved May 2022 from https://www.fda.gov/news-events/press-announcements/fda-considers-new-approach-improve-safe-disposal-prescription-opioid-analgesics-decrease-unnecessary; Federal Register. (2022). Providing mail-back envelopes and education on safe disposal with opioid analgesics dispensed in an outpatient setting; establishment of a public docket; request for comments. Retrieved May 2022 from https://www.federalregister.gov/documents/2022/04/21/2022-08372/providing-mail-back-envelopes-and-education-on-safe-disposal-with-opioid-analgesics-dispensed-in-an)Released: May 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - April 2022
Follow-Up Analysis Shows that Adding Isatuximab to Treatment for Resistant Multiple Myeloma Provides Continued SurvivalThe addition of the anti-CD38 monoclonal antibody isatuximab to pomalidomide-dexamethasone treatment resulted in a greater than 6-month difference in median overall survival compared to treatment without isatuximab in relapsed and refractory multiple myeloma. This finding was reported in a prespecified second interim analysis of a key secondary endpoint in the ICARIA-MM study; results of that study supported the March 2020 approval of isatuximab for multiple myeloma.READ MORE...ICARIA-MM was a randomized, multicenter, open-label phase 3 study that enrolled adults with relapsed or refractory multiple myeloma who had received at least two previous lines of therapy. This therapy could include lenalidomide and a protease inhibitor, but no prior pomalidomide treatment was permitted. Patients were recruited from hospitals in 24 countries worldwide; 307 patients were randomly assigned to receive isatuximab plus pomalidomide-dexamethasone (n = 154) or to pomalidomide-dexamethasone alone (n = 153).Median overall survival was 24.6 months in the isatuximab plus pomalidomide-dexamethasone group and 17.7 months in the pomalidomide-dexamethasone group (hazard ratio [HR], 0.76). Serious treatment-emergent adverse effects were observed in 111 patients (73%) who received isatuximab plus pomalidomide-dexamethasone, and in 90 patients (60%) who received pomalidomide-dexamethasone. At cutoff of follow-up, 18% of the patients in the isatuximab plus pomalidomide-dexamethasone group and 8% of patients in the pomalidomide-dexamethasone group remained on the study treatment; death had occurred in 60% of patients. Updated progression-free survival analysis showed a median duration of progression-free survival of 11.1 months with isatuximab plus pomalidomide-dexamethasone and of 5.9 months with pomalidomide-dexamethasone (HR, 0.60).This improved survival supports the assertion that this treatment should be considered as standard of care for patients with multiple myeloma refractory to usual treatments (lenalidomide and protease inhibitors). (Richardson, P. G., Perrot, A., et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): Follow-up analysis of a randomised phase 3 study. (2022). Lancet Oncol, 23(3), 416-427. Retrieved March 2022 from https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00019-5/fulltext; Stenger, M. (2022). Interim analysis of overall survival in ICARIA-MM: Addition of isatuximab to pomalidomide/dexamethasone in relapsed or refractory multiple myeloma. The ASCOT Post. Retrieved March 2022 from https://ascopost.com/news/march-2022/interim-analysis-of-overall-survival-in-icaria-mm-addition-of-isatuximab-to-pomalidomidedexamethasone-in-relapsed-or-refractory-multiple-myeloma/#:~:text=The%20investigators%20concluded%2C%20%E2%80%9CAddition%20of,refractory%20or%20relapsed%20multiple%20myeloma)Released: April 2022Nursing Drug Handbook© 2022 Wolters KluwerRelying on Informal Sources of Information Increases Vaccine Hesitancy in Medicare BeneficiariesCirculation of misleading information on the COVID-19 vaccines on social media is considered one of the important causes for vaccine hesitancy. A study published in the Journal of the American Geriatric Society examined this hypothesis, and further sought to learn if reliance on multiple sources of information about COVID-19 was associated with less vaccine hesitancy among a sample of Medicare beneficiaries.READ MORE...The Medicare Current Beneficiary Survey (MCBS) contains data collected from a nationally representative sample of Medicare beneficiaries. The MCBS COVID-19 Fall 2020 Rapid Response Supplement, administered between October and November 2020, included a study cohort of 7,278 beneficiaries, a weighted sample representing 43,829,153 community-dwelling Medicare beneficiaries. Respondents answered questions about their sources of COVID-19 information and about their presumptive vaccine uptake (the questions were posed before vaccines were available). The survey aimed to determine COVID-19 vaccine hesitancy, scored as 1 if they answered, “probably not, definitely not, not sure” and 0 if they answered, “definitely, probably,” to the question “Would you get a COVID-19 vaccine if available?” Then they analyzed these findings according to key independent variables: the reliance on formal vs. informal sources of COVID-19 information, and the total number of information sources the respondent relies on, both formal and informal. Informal sources include social media, the Internet, or friends and family. Formal sources include traditional news outlets, government guidance, and information from medical professionals.The survey demonstrated that 16% of respondents (n = 1,231) reported getting their information about COVID-19 from informal information sources. Vaccine hesitancy was found in 44% of those relying on informal information sources vs. 38% of those who reported relying on formal information sources. Relying on informal sources was associated with a 29% higher odds of vaccine hesitancy (OR, 1.29). Relying on more, varied sources of information on COVID-19 was associated with lower odds of vaccine hesitancy, with a decrease of 0.91 in odds ratio for each additional source used.These results can provide insights to guide future efforts that aim to build up positive attitudes toward the vaccine and to increase vaccine uptake. In addition, they add support to the importance of taking precautionary measures to address false anti-vaccination claims. The study has limitations, as the survey didn’t include Medicare beneficiaries living in long-term care facilities and, importantly, was conducted before the vaccines were available. But later events have strengthened the evidence for its hypothesis proving true. (Kim, J., Kim, Y., et al. (2022). Source of information on COVID-19 vaccine and vaccine hesitancy among U.S. Medicare beneficiaries. J Am Geriatr Soc, 70(3), 677–680. Retrieved March 2022 from https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.17619)Released: April 2022Nursing Drug Handbook© 2022 Wolters KluwerWHO-Recommended Essential Medicines Not Always Available in Age-Appropriate Formulations for Young ChildrenThe World Health Organization (WHO) compiles and disseminates the WHO Essential Medicines List for children (EMLc) to guide the selection of medicines for use in children ages 0 to 12. Essential medications are defined as those necessary to prevent, treat, or manage the most prevalent diseases in a population. The EMLc is an important tool; for most low- and middle-income countries, the list serves as a template for national drug formularies. But a study published in Archives of Diseases in Childhood documents that most essential enteral medications listed in both the 2011 and 2019 EMLc couldn’t be considered age-appropriate for children under age 6.READ MORE...The study sought to determine the appropriateness of all enteral formulations on the EMLc by assessing two important characteristics: swallowability and dose adaptability. Researchers defined age-appropriate formulations as ones which “a child of a specified age or age-group would have the natural ability to use (either directly or indirectly) without the product having to be altered from its original presentation before administration.” Two pharmacists evaluated each of the recommended medications for each of the five age-groups under age 12 and ranked them as 1 (not age-appropriate), 2 (possibly age-appropriate), or 3 (age-appropriate) for those two characteristics.When assessing swallowing ability, they used certain criteria to gain consistency in their evaluations:Liquids, oral powders/granules, dispersible tablets: appropriate from birth, with dose volumes under 10 mL being acceptable under age 5Crushed tablets, sprinkle capsules: appropriate from age 6 months, or the age at which a child can swallow solidsChewable tablets, dispersible tablets: appropriate from age 2, or the age at which a child can safely chew and swallow tabletsConventional tablets and capsules: not appropriate for those under age 5; children this age are incapable of swallowing the medication safelyEffervescent tablets: not appropriate for those under age 5, because of the need for large volumes, typically in excess of 100 to 200 mL.To examine dose adaptability, the evaluators compared the recommended doses in mg/kg body weight or mg/m2 BSA for each essential medicine, as given in the WHO formulary, to the mean body weight or BSA for each age-group. They determined whether the volume of a liquid or size/amount of a solid form was appropriate to deliver the recommended dose to a given age-group.The evaluation found that, in the 2011 edition of the EMLc, 77% of formulations were appropriate for older children (older than age 6). But for younger children, those percentages dropped: 34% were age-appropriate for preschoolers (ages 3 to 5), 30% were age-appropriate for toddlers (ages 1 to 2), 22% were age-appropriate for infants (ages 28 days to 11 months), and 15% were age-appropriate for neonates (ages 0 to 27 days). Overall, these proportions held true for EMLc 2019. The researchers further found that 55% of the active pharmaceutical ingredients were available in a variety of formulations that resulted in the drug being appropriate for all age-groups and that at least 47% had, at the minimum, one formulation (usually an oral liquid) that was considered appropriate for all age groups. But in practice, especially in low-income countries, the whole range of formulations aren’t readily commercially available. For example, only 33% of drugs on the 2011 EMLc were available in Nigeria in formulations suitable for younger children, significantly lower than the 52% to 57% availability seen in countries like the United States, the United Kingdom, and France.Going forward, all formulations included in the EMLc should be assessed for age-appropriateness, and that assessment should be a guide to development of new products or alternative administration strategies. Ensuring that age-appropriate formulations are actually available can help support decisions and strategies intended to provide access to essential medicines. (Orubu, E. S., Duncan, J., et al. (2022). WHO essential medicines for children 2011-2019: Age-appropriateness of enteral formulations. Arch Dis Child, 107, 317–322. Retrieved March 2022 from https://adc.bmj.com/content/107/4/317)Released: April 2022Nursing Drug Handbook© 2022 Wolters KluwerCardioselective Beta Blockers a Better Choice for Patients with COPD Who Experience Heart AttackBeta blockers are known to reduce death and adverse cardiac events in patients after a myocardial infarction (MI). But clinicians hesitate to prescribe beta blockers in patients with respiratory disease who experience an MI, fearing that the beta blockers might precipitate bronchospasm and reduced pulmonary function in these patients. A retrospective Taiwanese study investigated use of beta blockers, and specifically of cardioselective beta blockers, in patients with chronic obstructive pulmonary disease (COPD) being treated in hospital after their first-ever MI.READ MORE...The study identified 65,699 patients with COPD in the Taiwan National Health Insurance Research Database who were prescribed beta blockers after their first MI from January 2001 to December 2013. After excluding patients who had been treated with both cardioselective and nonselective beta blockers, those younger than age 20, those who died during their hospitalization for that initial MI, and those who had been followed up for less than 90 days, the study enrolled 14,789 patients. The researchers examined patient records for all-cause mortality and for the secondary outcomes of hospitalization for heart failure, incidence of major cardiac or cerebrovascular events (MACCE), including death, revascularization, repeated MI, or ischemic stroke, and of major adverse pulmonary events (MAPE), such as exacerbations of COPD and hospitalizations due to pneumonia. The patients were categorized into two groups: 7,247 patients were prescribed cardioselective beta blockers during that hospitalization and 7,542 patients were prescribed nonselective beta blockers. There were no significant differences in most baseline characteristics between the two groups, and no significant differences in hospital treatment for the initial MI, including similar admission rates and ICU stays, the need for inotropic agents and intubation, and interventions for coronary artery disease.The patients who were prescribed cardioselective beta blockers had a lower risk of all-cause mortality than those who were prescribed nonselective beta blockers—8.9 vs. 9.6 events per 100 person-years (HR, 0.93), and of MACCE—13.2 vs. 13.9 events per 100 person-years (HR, 0.96), as well as of hospitalization for heart failure—3.3 vs. 3.8 events per 100 person-years (HR, 0.89). The incidence of MAPE was significantly lower in the cardioselective group compared to the nonselective group: 10 vs. 10.8 events per 100 person-years (HR, 0.94).Similar results were found in subgroup analysis between those prescribed the cardioselective beta blocker bisoprolol (n = 5,644; 74% of patients receiving cardioselective beta blockers) and those prescribed the nonselective beta blocker carvedilol (n = 4,881; 64.7% of patients receiving nonselective beta blockers). All-cause mortality was significantly lower with bisoprolol than with carvedilol at the end of follow-up—9.3 vs. 10.3 events per 100 person-years (HR, 0.90), as was hospitalization for heart failure—3.5 vs. 4.4 events per 100 person-years (HR, 0.84), and MAPE—10.5 vs. 11.5 events per 100 person-years (HR, 0.94). Incidence of MACCE was not significantly different between the two drugs: 14 vs. 14.7 events per 100 person-years (HR, 0.96).These results strongly suggest that patients with COPD who experience an MI can be prescribed beta blockers, but they should be cardioselective beta blockers, as they are safer and more effective than nonselective beta blockers in this population. The study has limitations, as it’s a retrospective study only; a randomized, controlled trial is still needed to confirm these beneficial effects. (Chung, C-M., Lin, M-S., et al. (2022). Cardioselective versus nonselective ß-blockers after myocardial infarction in adults with chronic obstructive pulmonary disease. Mayo Clinic Proceed, 97(3), 531-546. Retrieved March 2022 from https://www.mayoclinicproceedings.org/article/S0025-6196(21)00622-4/fulltext#secsectitle0010)Released: April 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - March 2022
Combination of Inhaled Corticosteroids and Long-Acting Beta Agonists Improves Lung Function in Children Born PrematurelyCombination therapy with an inhaled corticosteroid (ICS) and a long-acting beta agonist (LABA) significantly improved lung spirometry results in children with significant lung function deficits compared with either steroids alone or placebo. These are results of a study conducted in Wales, at the Children’s Hospital for Wales in Cardiff, which tested the combination in school-aged children who had been born prematurely (before 34 weeks’ gestation). These children are known to be at increased risk of decreases in future lung function, especially when they are diagnosed with bronchopulmonary dysplasia (BPD) in infancy.READ MORE...The randomized controlled trial enrolled 53 children ages 7 to 14, who were born at <34 weeks’ gestation, with low lung function (pretreatment %FEV1 [percent forced expiratory volume in 1 second] ≤85%) and examined whether 12 weeks of treatment would improve incentive spirometry results and exercise capacity. Approximately 40% of participants in the study had BPD; other signs of respiratory morbidity were similar in all groups. They were randomized to the ICS fluticasone 50 mcg plus placebo (n = 20), fluticasone 50 mcg plus the LABA salmeterol 25 mcg (n = 19), and placebo (n = 14), all given as 2 puffs per day for 12 weeks.Both ICS and ICS/LABA combination treatment produced improvements in %FEV1, both significantly greater than placebo. The increase in %FEV1 with ICS was 7.7% higher than placebo; with the ICS/LABA combination, the increase was twice as great: 14.1% higher than placebo. The %FEV1 increased from 75.1% to 81.1% (mean difference, 6.0%) in the ICS group and from 77.9% to 86.2% (mean difference, 8.3%) in the ICS/LABA group. Active treatment decreased the fractional exhaled nitric oxide (FENO) and increased postexercise bronchodilator response but didn’t improve exercise capacity. The FENO dropped from 29.8 ppb (parts per billion) to 15.7 ppb in the ICS group and from 25.2 ppb to 15.9 ppb in the ICS/LABA group. FENO didn’t decrease after placebo.The combination ICS/LABA may produce its greater effects by targeting both the structural changes in the respiratory system of children born preterm and inflammatory processes, as suggested by the improvement in FENO. The lack of improvement in exercise capacity in this trial may have resulted from the test not being sensitive enough to note small differences, especially in a population that might have been habitually inactive. (Goulden, N., et al. (2022). Inhaled corticosteroids alone and in combination with long-acting β2 receptor agonists to treat reduced lung function in preterm-born children: A randomized clinical trial. JAMA Pediatr,176(2), 133–141. Retrieved March 2022 from https://jamanetwork.com/journals/jamapediatrics/fullarticle/2786783)Released: March 2022Nursing Drug Handbook© 2022 Wolters KluwerThird Dose Boosts COVID-19 Vaccine Efficacy in Patients with CLLIn an Israeli study, in patients with CLL (chronic lymphocytic leukemia) who had failed to achieve an antibody response to two doses of an mRNA vaccine against SARS-CoV2, close to a quarter of the patients in the study became seropositive after a third dose.Patients were enrolled from July 2020 to August 2021; eligible patients had a diagnosis of CLL or small lymphocytic lymphoma (SLL), were age 18 or older, had no know history of SARS-CoV2 infection, and had failed to respond to a second dose of a vaccine against SARS-CoV2. The 172 patients were classified into three groups: the treatment-naive (n = 40, 23.3%), those who were on active treatment for CLL/SLL (n = 100, 58.1%), and those not currently receiving treatment who had been treated previously (n = 32, 18.6%). Among those who had received treatment in the past, 24 (75%) were in remission, 18 of them in complete remission, and 8 (25%) were experiencing relapse. Patients on active treatment included 59 who were receiving a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib) and 39 receiving venetoclax either with or without an anti-CD20 antibody (rituximab or obinutuzumab).READ MORE...Serologic response after the third vaccine dose correlated with the degree of immunosuppression accompanying CLL in each patient. Antibody response was seen in 41/172 patients (23.8%), with a median antibody level of 2 AU/mL. Treatment-naïve patients and those who were no longer receiving treatment for their illness had higher response rates and higher antibody levels: 16/40 (40%) of treatment-naive patients had antibody response, with median antibody level of 8 AU/mL, and 13/32 of patients no longer on treatment, with median antibody level of 6 AU/mL. In actively treated patients, response rates were lower (n = 12/100, 12%), with a median antibody level of 0 AU/mL.Among patients who had previously received treatment, serologic response rates of those in complete remission was 38.9%, in partial remission was 50%, and those experiencing relapse was 37.5%. Among those on active treatment, those receiving BTK inhibitors had a response rate of 15.3% and those receiving venetoclax with or without anti-CD20 antibodies had a response rate of 7.7%. Only 1 of 28 patients (3.6%) treated with anti-CD20 antibodies within 12 months of the third dose responded, compared to 15/63 (22.7%) of those treated with anti-CD20 antibodies at least 12 months before. Each month that elapsed from the end of anti-CD20 antibody treatment increased odds for serologic response to the vaccine by 1.03 times.The study authors suggested that an additional booster be considered for all patients with CLL who had been vaccinated with mRNA vaccines. Since results were lowest in those on active therapy, they suggest that it may be appropriate to delay the start of treatment to allow for vaccination before treatment produces immunosuppression. (Herishanu, Y., et al. (2022). Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination. Blood, 139(5): 678–685. Retrieved March 2022 from https://ashpublications.org/blood/article/139/5/678/482889/Efficacy-of-a-third-BNT162b2-mRNA-COVID-19-vaccine?searchresult=1)Released: March 2022Nursing Drug Handbook© 2022 Wolters KluwerStatin Intolerance May Be OverestimatedFindings of a recent meta-analysis indicate that intolerance to statin therapy is much less common than previous data suggested, showing that fewer than 1 in 10 patients are unable to tolerate the cholesterol-lowering treatment. Nonadherence to statin therapy due to the fear of statin intolerance results in suboptimal treatment for dyslipidemia and a high risk of cardiovascular events.READ MORE...The meta-analysis of 176 studies (involving more than 4 million patients) published in the European Heart Journal found that 9.1% of patients had statin intolerance. The analysis included 112 randomized clinical trials and 64 cohort studies of statin-treated patients followed for a mean of 19 months. It estimated the overall prevalence of statin intolerance and also aimed to determine prevalence according to differing international diagnostic criteria and in different disease settings. In addition, the researchers identified possible risk factors for statin intolerance.In published studies, the mean prevalence of statin intolerance in randomized clinical trials was 4.9%, and in cohort studies was 17%. The higher prevalence in cohort studies, which is as high as 30%, is most likely an overestimate and could be attributable to “nocebo” effects. On the other hand, it’s possible that exclusion criteria in randomized controlled trials may result in underestimates, as older patients and those with comorbidities associated with statin intolerance are excluded. When examining prevalence of intolerance based on varied diagnostic criteria, it was 7% in studies that used the National Lipid Association (NLA) criteria, which defines intolerance as an adverse effect that limits quality of life and leads to a decision to decrease or stop the statin. Prevalence under International Lipid Expert Panel criteria, which were similar to those of NLA, was 6.7%. Under the stricter definition provided by the European Atherosclerosis Society, which focused specifically on statin-associated muscle symptoms (SAMS) and CK elevations, prevalence was 5.9%.Increased risk of statin intolerance was associated with demographic characteristics and with clinical indices. Women had a 47% higher relative risk (RR) of statin intolerance compared to men, and the RR was 31.2% higher in those over age 65 than in younger patients. Positive associations were also seen in patients with obesity (RR, 30.6%), diabetes (RR, 26.6%), and hypothyroidism (RR, 37.6%). The positive associations in Black and Asian patients and in those with chronic liver and kidney disease were smaller, but still clinically significant.Nonadherence with statin therapy is most commonly ascribed to muscle pain, but it’s important for clinicians to determine whether that muscle pain is actually related to statin use. The criteria necessary for a diagnosis of SAMS are that the symptoms (pain, weakness, or cramps, often with CK changes or severe myopathy) must appear within 12 weeks after treatment initiation or dose increase. Clinicians should explore whether muscle pain at later stages results from interactions with a new medication or as a result of a comorbid condition that’s not controlled. (O’Riordan, M. (2022). Statin intolerance overestimated – Only ‘small number’ get side effects: Meta-analysis. TCTmd.com. Retrieved March 2022 from https://www.tctmd.com/news/statin-intolerance-overestimated-only-small-number-get-side-effects-meta-analysisBytyҫi, I., et al. (2022). Prevalence of statin intolerance: A meta-analysis. Eur Heart J, 1–16. Retrieved March 2022 from https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac015/6529098?login=false)Released: March 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - February 2022
Efficacy of Outpatient Treatment with Ciclesonide in COVID-19Systemic corticosteroids have been used to treat severe COVID-19 infection, resulting in lower 28-day mortality rates in these patients. But the role of inhaled steroids in mild to moderate COVID-19 infection is less clear. Inhaled ciclesonide is a promising candidate: it’s been shown to have anti-inflammatory properties in lung and bronchial structures through inhibition of the PAK1 enzyme in cells, a known pathogenic pathway for COVID-19.READ MORE...A phase 3, multicenter, double-blind, randomized clinical trial conducted in 400 nonhospitalized patients with mild to moderate COVID-19 infection from June to November 2020 compared inhaled ciclesonide to placebo. Patients were randomly assigned to receive ciclesonide (n = 197) by metered-dose inhaler, 160 mcg/actuation, 2 actuations b.i.d., for a total daily dose of 640 mcg, or placebo (N = 203) for 30 days. The primary endpoint was time to alleviation of COVID-19-related symptoms, including cough, dyspnea, fever, shaking chills, muscle pains, headache, sore throat, and lack of sense of taste or smell). The study also followed the patients to determine if they had subsequent emergency department (ED) visits or hospital admissions for reasons attributable to COVID-19. Patients were eligible for the study if they were older than age 12, were positive for SARS-Cov2 but not at risk for hospitalization, with an oxygen saturation of at least 93% on room air and at least one of the common symptoms of COVID-19 infection. They were told to notify researchers if they experienced an ED visit or hospitalization during the study; they were instructed to seek ED evaluation if their oxygen saturation level fell below 92%. All patients took the study medication for 30 days, even if symptoms resolved earlier.The median time to alleviation of all COVID-related symptoms was 19.0 days in both the ciclesonide and placebo arms. There was also no difference in resolution of symptoms by day 30 (odds ratio, 1.28). The most common symptoms on day 30 were cough (11.7% vs. 12.3%), muscle pain (9.6% vs. 8.9%), and dyspnea (10.2% vs. 7.9%). But though there were no differences in resolution of symptoms, those treated with inhaled ciclesonide had fewer subsequent ED visits or hospital admissions for reasons related to COVID-19 by day 30 compared to those receiving placebo (1.0% vs. 5.4%; odds ratio, 0.18).An important consideration is that it’s not uncommon for patients with COVID-19 infection to continue to experience lingering symptoms for some time; as a result, testing for this endpoint may have masked a significant portion of the population who were able to safely return to usual life and who were no longer at risk for viral transmission. The secondary outcome of fewer ED visits or hospitalizations may be more relevant, offering evidence that inhaled ciclesonide or other steroids are a low-cost intervention that can prevent such events. (Clemency, B. M., et al. (2021). Efficacy of inhaled ciclesonide for outpatient treatment of adolescents and adults with symptomatic COVID-19: A randomized clinical trial. JAMA Intern Med, 182(1), 42–49. Retrieved February 2022 from https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2786012)Released: February 2022Nursing Drug Handbook© 2022 Wolters KluwerWhich Vaccine for COVID-19 Booster?Although the vaccines against SARS-CoV2 that have been available in the United States since early 2021 provide high levels of protection against severe illness and death resulting from COVID-19 infection, the increasing number of breakthrough infections in fully vaccinated persons from the delta variant starting in late spring 2021, followed by the even more transmissible omicron variant, raised concerns about waning immunity. The phase 1-2, open-label MixNMatch study, conducted at 10 sites in the United States, was designed to assist in the development of booster strategies during the ongoing pandemic. It assessed both homologous boosters (the same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in persons who had completed a COVID-19 vaccination regimen at least 12 weeks earlier and had no reported history of SARS-CoV2 infection.READ MORE...MixNMatch enrolled 458 people, who received a booster from one of three vaccines: 154 received the Moderna mRNA vaccine, 100 mcg; 150 received the Johnson & Johnson/Janssen vaccine, 5 × 1010 virus particles; and 150 received the Pfizer/BioNtech vaccine, 30 mcg. Both homologous and heterologous booster vaccines had an acceptable safety profile and immunogenicity. As with the primary series of vaccines, mild adverse effects—myalgia, headache, malaise, injection-site pain—were common. Reactogenicity was similar to that seen in previous evaluations of the vaccines and didn’t differ between homologous and heterologous boosters. In addition, all boosters were immunogenic in participants, regardless of which primary vaccine regimen they had received.The factor increases after booster in both binding and neutralizing antibody titers were similar or greater after heterologous boosters than after homologous boosters. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20; in heterologous boosters, they increased by a factor of 5 to 55. Increases were greatest in participants who received an mRNA booster after a primary J&J/Janssen vaccination (34 with Pfizer/BioNTech, 55 with Moderna). Interestingly, binding antibody titers peaked at day 15 for those who received an mRNA vaccine as a booster and were similar or declining on day 29; for those who received the J&J/Janssen vaccine as a booster, titers on day 29 were similar to those measured on day 15.Spike-specific T-cell responses increased in all combinations but the homologous J&J/Janssen-boosted subgroup. CD8+ T-cell levels were more durable in participants whose primary vaccine was J&J/Janssen, and heterologous booster with that vaccine substantially increased spike-specific CD8+ T-cells in those who had previously received the mRNA vaccines. These vaccine-elicited spike-specific T-cell responses may contribute to the antibody response and the prevention of severe disease in cases of breakthrough infections.These data strongly suggest that both homologous and heterologous booster vaccine doses will increase protective efficacy against symptomatic SARS-CoV2 infection. The data show that an immune response will be generated for each of these vaccines used as a booster regardless of the primary vaccination regimen. (Atmar, R. L., et al. (2022). Homologous and heterologous covid-19 booster vaccinations. New Engl J Med. Retrieved February 2022 from https://www.nejm.org/doi/full/10.1056/NEJMoa2116414?query=TOC)Released: February 2022Nursing Drug Handbook© 2022 Wolters KluwerOral Penicillin Recommended for Treatment of High-Risk Rheumatic Heart DiseaseMore than 39 million people worldwide have rheumatic heart disease, a condition in which heart valves are permanently damaged as a result of a bout of rheumatic fever, which can occur if strep throat or scarlet fever is inadequately treated. Most cases of rheumatic heart disease, especially in lower income nations, aren’t diagnosed until after severe valvular heart disease or other CV complications have already developed.READ MORE...The recommended treatment for rheumatic heart disease is a long-term (that is, 10 years or longer) regimen of penicillin G benzathine, given by IM injection every 3 to 4 weeks. For many years, death after these injections were ascribed to anaphylaxis, but evidence is growing that points to a different cause: cardiac compromise. Such a shift in perspective has important ramifications for the management of this disease, and an American Heart Association Presidential Advisory statement addresses this, recommending oral penicillin as a safer option for some patients with rheumatic heart disease at high risk for a vasovagal response and resultant cardiac compromise.The advisory panel divided patients into low-risk and elevated-risk groups, based on symptoms and the severity of the underlying valvular heart disease. The risks of cardiac compromise are highest among patients with severe valvular disease, as they have low CV reserves and may not compensate well to pain on injection. Patients with severe mitral stenosis, who depend on increased preload to maintain cardiac output, are at highest risk.The advisory panel suggests that those with a low risk of cardiac compromise and no history of penicillin allergy or anaphylaxis can safely continue to receive the injectable penicillin G benzathine, and they advocate a multifaceted strategy for vasovagal reaction risk reduction in those patients. Noting that pain or fear of the penicillin injection, along with physiologic and other stresses, such as dehydration, drives the vasovagal response, the advisory panel recommends the following protocols:Reduce injection pain and anxiety by applying pressure and ice to the injection site and administering acetaminophen or NSAIDs.Ensure that patients are well-hydrated and have eaten a small amount of food in the hour before injection.To reduce the risk of postural hypotension and fainting, administer the injection with the patient supine.Ensure that those administering the injection can recognize and quickly treat any cardiac symptoms.For those in the elevated-risk group, the advisory panel states that treatment with oral penicillin should be strongly considered. They note that making a change from injectable to oral penicillin prophylaxis carries its own challenges, particularly requiring a commitment from governments to ensure its availability and from health care providers to educate patients. (American Heart Association. (2022). Oral penicillin, not injectable, advised for people with high-risk rheumatic heart disease. Retrieved February 2022 from https://newsroom.heart.org/news/oral-penicillin-not-injectable-advised-for-people-with-high-risk-rheumatic-heart-disease?preview=326b; Sanyahumbi, A., et al. (2022). Penicillin reactions in patients with severe rheumatic heart disease: A Presidential Advisory from the American Heart Association. J Am Heart Assoc. Retrieved February 2022 from https://www.ahajournals.org/doi/10.1161/JAHA.121.024517)Released: February 2022Nursing Drug Handbook© 2022 Wolters KluwerInhaled Treprostinil Continues to Prevent Progression Events in Pulmonary Hypertension on Post Hoc AnalysisInterstitial lung disease complicated by pulmonary hypertension (PH-ILD) results in worse outcomes than other forms of ILD: worsened functional status, increased requirements for supplemental oxygen, increased health care resource use, and increased mortality. INCREASE, a 16-week, phase 3, multicenter, double-blind, placebo-controlled study, showed a benefit from inhaled treprostinil, a stable prostacyclin analogue with potent vasodilation on pulmonary vasculature, in patients with PH-ILD. The study’s primary endpoint—change in 6-minute walking distance from baseline, a measure of exercise tolerance—showed improvement of 31 meters in the active treatment group. In addition, treatment with inhaled treprostinil resulted in a delayed time to first disease progression compared to placebo, and fewer clinical worsening events.READ MORE...Post hoc analysis sought to determine the efficacy of continuing inhaled treprostinil use after disease progression. It therefore evaluated the effects of continued treatment on the frequency of multiple disease progression events. On analysis, 147 disease progression events occurred in the inhaled treprostinil group (in 89 of 163 patients; 55%) compared with 215 events in the placebo group (in 109 of 163 patients; 67%). The incidence of each type of disease progression event was also lower in the inhaled treprostinil group vs. placebo:15% decline in 6-minute walking distance (45 vs. 64 events)exacerbation of lung disease (48 vs. 72 events)10% decline in forced vital capacity (19 vs. 33 events)cardiopulmonary hospitalization (23 vs. 33 events)death (10 vs. 12 events).Fewer patients receiving inhaled treprostinil experienced multiple progression events compared with those receiving the placebo (35 patients, 22% vs. 58 patients, 36%).This comprehensive analysis of all disease progression events in the INCREASE study provides a more complete view of the benefits of inhaled treprostinil in patients with PH-ILD and supports the continuation of this therapy in those patients who do experience a clinical worsening event. (Nathan, S. D., et al. (2021). Efficacy of inhaled treprostinil on multiple disease progression events in patients with pulmonary hypertension due to parenchymal lung disease in the INCREASE trial. Am J Respir Crit Care Med, 205(2), 198–207. Retrieved February 2022 from https://www.atsjournals.org/doi/full/10.1164/rccm.202107-1766OC; Behr, J. (2022). Inhaled treprostinil in pulmonary hypertension in the context of interstitial lung disease: A success, finally. Am J Respir Crit Care Med, 205(2), 144–145. Retrieved February 2022 from https://www.atsjournals.org/doi/full/10.1164/rccm.202110-2444ED)Released: February 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - January 2022
Apixaban a Better Choice for Atrial Fibrillation in Older AdultsA retrospective cohort study offered compelling evidence that the direct oral anticoagulant (DOAC) apixaban carries a smaller risk of bleeding complications than rivaroxaban. DOACs have replaced warfarin as the treatment of choice for stroke prevention in atrial fibrillation, but they haven’t been tested head-to-head in randomized clinical trials. Choice of which DOAC to use has come down to clinician preference; this study aimed to determine differences between the two DOACs, rivaroxaban and apixaban.READ MORE...The observational study looked at claims data on 581,451 Medicare beneficiaries (mean age, 77 years; 50.2% women) with atrial fibrillation who initiated treatment with a DOAC between January 2013 and November 2018. Apixaban was given to 353,879 patients (61%); 227,572 patients (39%) received rivaroxaban. About 23.1% of patients (n = 134,393) received a reduced dose of either drug. The claims data was examined for evidence of the primary outcome, a composite of major ischemic events (stroke and systemic embolism) and major hemorrhagic events (intracerebral hemorrhage, other intracranial bleeding, and fatal extracranial bleeding).The effectiveness of the two drugs was similar, but new users of rivaroxaban had a greater risk of a range of adverse outcomes compared with those started on apixaban. Through median follow-up of about 6 months, the rate of the primary outcome was higher with rivaroxaban (16.1 per 1,000 person-years) vs. apixaban (13.4 per 1,000 person-years). Breaking down the composite shows that rivaroxaban was associated both with more major ischemic events than apixaban (8.6 vs. 7.6 per 1,000 person-years; hazard ratio [HR], 1.12) and with more major hemorrhagic events (7.5 vs. 5.9 per 1,000 person-years; HR, 1.26). Other key outcomes also favored apixaban: fatal extracranial bleeding (1.4 per 1,000 person-years with rivaroxaban vs. 1.0 per 1,000 person-years with apixaban; HR, 1.41), nonfatal extracranial bleeding (39.7 per 1,000 person-years with rivaroxaban vs. 18.5 per 1,000 person-years with apixaban; HR, 2.07), fatal ischemic or hemorrhagic events (4.5 vs. 3.3 per 1,000 person-years; HR, 1.34), and total mortality (44.2 vs. 41.0 per 1,000 person-years; HR, 1.06). The risk of the primary outcome was higher with rivaroxaban whether the patients received a reduced dose (27.4 vs. 2.1 per 1,000 person-years; HR, 1.28) or a standard dose (13.2 vs. 11.4 per 1,000 person-years; HR, 1.13).This new analysis, because of its size, allowed investigators to examine differences in events that occurred less frequently, to combine ischemic and hemorrhagic events to get a risk-benefit picture, and to include analysis of different dosage strengths. These results demonstrate that although the two drugs are comparable in efficacy, apixaban is superior in safety. (Neale, T. (2021). Apixaban appears safer, more effective than rivaroxaban in Medicare study. TCTMD. Retrieved January 2022 from https://www.tctmd.com/news/apixaban-appears-safer-more-effective-rivaroxaban-medicare-study; Ray, W. A., et al. (2021). Association of rivaroxaban vs apixaban with major ischemic or hemorrhagic events in patients with atrial fibrillation. JAMA, 326(23), 2395–2404. Retrieved January 2022 from https://jamanetwork.com/journals/jama/article-abstract/2787319)Released: January 2022 Nursing Drug Handbook © 2022 Wolters KluwerEtrolizumab for Ulcerative ColitisAnti-integrin therapy is used to treat ulcerative colitis because it blocks the effect of the cell-surface glycoprotein integrin on the surface of leukocytes and endothelial cell adhesion molecules, thereby inhibiting leukocytes from interacting with the intestinal mucosa. The Lancet Gastroenterology and Hepatology published results of studies that evaluated etrolizumab, a gut-targeted anti-β7 integrin monoclonal antibody, as induction and maintenance therapy for ulcerative colitis. The HIBISCUS studies compared the efficacy and safety of etrolizumab to the tumor necrosis factor (TNF) blocker adalimumab and placebo for induction of remission in patients with moderate to severe ulcerative colitis. Another study, LAUREL, compared etrolizumab to placebo as maintenance therapy.READ MORE...HIBISCUS I and II followed up on findings of a phase 2 study that indicated that etrolizumab significantly improved induction of clinical remission compared to placebo. The HIBISCUS studies, identically designed, multicenter, phase 3, randomized, double-blind, placebo-controlled and active-controlled studies, enrolled patients with moderate to severe ulcerative colitis, with a Mayo Clinic total score of 6 to 12 and endoscopic subscore of 2 or greater, rectal bleeding subscore of 1 or greater, and a stool frequency subscore of 1 or greater, who hadn’t previously been treated with TNF blockers. Patients were randomly assigned to subcutaneous etrolizumab 105 mg once every 4 weeks (n = 144 in HIBISCUS I and 143 in HIBISCUS II), to subcutaneous adalimumab 160 mg on day 1, 80 mg at week 2, and 40 mg at weeks 4, 6, and 8 (n = 142 in HIBISCUS I and 143 in HIBISCUS II), or to placebo (n = 72 in HIBISCUS I and 72 in HIBISCUS II).The studies tested for induction of remission at week 10, defined as a Mayo Clinic total score of 2 or lower, with individual subscores of 1 or lower, including a rectal bleeding subscore of 0. Posted analysis of both studies were examined for several clinical and endoscopic endpoints. Etrolizumab was found to be significantly superior to placebo for induction of remission in HIBISCUS I, but not in HIBISCUS II. In HIBISCUS I, 28 patients (19.4%) in the etrolizumab group and 5 patients (6.9%) in the placebo group were in remission by week 10. On pooled analysis, treatment with etrolizumab was not superior to the TNF blocker adalimumab for induction of remission, endoscopic improvement, clinical response, histologic remission, or endoscopic remission.LAUREL, a randomized, placebo-controlled, double-blind, phase 3 study, examined etrolizumab and compared it to placebo for maintenance of remission. The study enrolled adults with an established diagnosis of moderate to severe ulcerative colitis for at least 3 months, corroborated by clinical and endoscopic evidence. After an open-label induction phase, where 359 patients received subcutaneous etrolizumab 105 mg once every 4 weeks, if the participant had a clinical response at week 10, they were enrolled in the maintenance phase. The study found that 214 patients had such response, and were randomly assigned to receive subcutaneous etrolizumab 105 mg once every 4 weeks (n = 108) or placebo (n = 106) until week 62. At week 62, 32 patients (29.6%) in the etrolizumab group and 21 patients (20.6%) in the placebo group were in remission, a difference that is not clinically significant. (Rubin, D. T., et al. (2021). Etrolizumab versus adalimumab or placebo as induction therapy for moderately to severely active ulcerative colitis (HIBISCUS): Two phase 3 randomised, controlled trials. Lancet Gastroenterol Hepatol, 7(1), 17–27. Retrieved January 2022 from https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00338-1/fulltext;Vermeire, S, et al. (2021). Etrolizumab for maintenance therapy in patients with moderately to severely active ulcerative colitis (LAUREL): A randomized, placebo-controlled, double-blind, phase 3 study. Lancet Gastroenterol Hepatol, 7(1), 28–37. Retrieved January 2022 from https://www.thelancet.com/journals/langas/article/PIIS2468-1253(21)00295-8/fulltext)Released: January 2022 Nursing Drug Handbook © 2022 Wolters KluwerAccelerating Development of Gene Therapies for Rare DiseasesGene therapy represents hope for individuals with rare genetic disorders. But the very rarity of these disorders means that pharmaceutical companies cannot recover the costs incurred in the development of these therapies. The National Institutes for Health (NIH) have announced the launch of a consortium that aims to reduce some of those associated costs and to encourage companies to pursue gene therapies for rare disorders.READ MORE...The Bespoke Gene Therapy Consortium, or BGTC, will focus on adeno-associated virus (AAV) vectors, one of the safest platforms for gene delivery. BGTC aims to make AAV vector technology more accessible, pursuing an understanding of the life cycle of AAV, thereby facilitating optimization of vector generation and delivery. In addition, the consortium aims to streamline regulatory requirements: Because AAV vectors have been used before in clinical trials, it’s hoped that their use will shorten the path from animal models to human clinical trials. Working with the FDA, the consortium will explore methods of streamlining the FDA approval process for safe, effective gene therapies.The consortium includes the NIH in general as well as various components, including the National Institute for Neurological Disorders and Stroke and National Human Genome Research Institute, the FDA, and 15 partners. These partners include 10 pharma companies, including Biogen, Janssen, and Spark Therapeutics, and 5 nonprofits, including The Alliance for Regenerative Medicine, National Organization for Rare Disorders, CureDuchenne, American Society of Gene and Cell Therapy, and the National Institute for Innovation in Manufacturing Biopharmaceutics. The members of the consortium will contribute about $76 million for 5 years to support the BGTC-funded projects, with about half coming from NIH institutes and centers. BGTC will fund research to support 4 to 6 clinical trials, focusing on different rare diseases. It’s hoped that this approach will have substantial positive impacts on the larger gene therapy field. (Philippidis, A. (2021). National Institutes of Health, U.S. Food and Drug Administration, 15 partners to accelerate development of rare disease gene therapies. Human Gene Therapy, 32 (No. 23-24). Retrieved January 2022 from https://www.liebertpub.com/doi/full/10.1089/hum.2021.29188.bfs; Foundation for NIH. (n.d.). Accelerating Medicines Partnership® Bespoke Gene Therapy Consortium (AMP® BGTC). Retrieved January 2022 from https://fnih.org/our-programs/AMP/BGTC)Released: January 2022 Nursing Drug Handbook © 2022 Wolters Kluwer
Drug News Abstracts - December 2021
HPV Vaccine Safe for Young Survivors of CancerOnly 55% of U.S. adolescents are up-to-date on the recommended immunization schedule against human papillomavirus (HPV), well below the Healthy People 2030 goal of 80%. This low uptake is particularly of concern in young cancer survivors, whose risk of new cancers, including the cancers related to HPV, is higher than that of the general population.READ MORE...A study conducted by researchers from Emory University and the University of Alabama at Birmingham assessed the effectiveness, immunogenicity, and safety of the HPV vaccine in adolescent and young adult cancer survivors. The phase 2, single-arm, open-label, noninferiority trial enrolled 453 cancer survivors between ages 9 and 26, who had completed cancer treatment from 1 to 5 years previously and were considered in remission, who hadn’t received the HPV vaccine. The participants received three IM doses of either the quadrivalent vaccine (HPV4) or the nonavalent vaccine (HPV9), with mean age at first dose of 15.6 years. Data from published trials of the HPV vaccine in similar-age subjects (n = 26,486) were used as comparison. The study examined antibody response to the oncogenic HPV types 16 and 18 at month 7. Responses in the tested participants were considered noninferior if the lower bound of the adjusted 95% confidence interval was greater than 0.5 for the ratio of anti-HPV-16 and anti-HPV-18 geometric mean titers (GMT) in cancer survivors when compared to the general population.Responses were determined for male and female participants, and by age group (ages 9 to 15 and 16 to 26). The ratio of mean GMT for anti-HPV-16 and anti-HPV-18 in survivors versus the general population was greater than 1 for all subgroups in both vaccine cohorts, ranging from 1.64 for anti-HPV-16 in females ages 9 to 15 who received HPV9 to 4.77 for anti-HPV-18 in males ages 16 to 26 who received HPV4. Noninferiority criteria were met for each age and sex subgroup, except for anti-HPV-18 in females ages 16 to 26 who received HPV9. The safety profile among cancer survivors is also similar to that of the general population, with one or more adverse effects reported by 55% of participants: 51% who received HPV4 and 59% who received HPV9.These results provide evidence for use in this clinically vulnerable population and can encourage clinicians to discuss the HPV vaccine with cancer survivors. (Landier, W., et al. (2021). Immunogenicity and safety of the human papillomavirus vaccine in young survivors of cancer in the USA: A single-arm, open-label, phase 2, non-inferiority trial. Lancet Child Adolesc Health. Advance online publication. Retrieved December 2021 from https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00278-9/fulltext; Brewer, N. T., et al. (2021). Human papillomavirus vaccination for young survivors of cancer. Lancet Child Adolesc Health. Advance online publication. Retrieved December 2021 from https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(21)00312-6/fulltext)Released: December 2021Nursing Drug Handbook© 2021 Wolters KluwerNivolumab Improves Survival in Relapsed Malignant MesotheliomaThe CONFIRM trial is the first phase 3 trial to examine survival in patients with pleural or peritoneal mesothelioma whose disease had progressed after platinum-based chemotherapy. It demonstrated longer progression-free survival and overall survival with the anti-PD-L1 antibody nivolumab compared with placebo. Malignant mesothelioma is a universally lethal cancer that is usually caused by exposure to asbestos fibers. Since 2004, when pemetrexed and cisplatin were approved for treatment of pleural mesothelioma, no other agent has shown improved survival after disease progression in patients with the cancer.READ MORE...The study enrolled 333 patients with mesothelioma and ECOG performance status of 0-1, who had previously received first-line platinum chemotherapy and had radiologic evidence of disease progression. Mean age of patients was 70 years, with 76% male and 80% with ECOG status of 1; 316 patients (95%) had pleural mesothelioma, 293 (88%) had epithelioid histology, and 230 (69%) had been exposed to asbestos. All patients had received platinum-based chemotherapy; 97% had received pemetrexed. They were assigned to 240-mg nivolumab over 30 minutes IV every 2 weeks until disease progression or 12 months (n = 221) or to placebo (n = 111). Participants were assessed with computed tomography scans on day 1 of each 2-week cycle and 4 weeks after treatment discontinuation.Median follow-up was 11.6 months. By the date of preliminary analysis, 210 (63%) of the patients had experienced disease progression. Median progression-free survival in the nivolumab group was 3.0 months, compared to 1.8 months in the placebo group (hazard ratio [HR], 0.67). Progression-free survival at 1 year was 14.2% in the nivolumab group vs. 7.2% in the placebo group. Median overall survival in the nivolumab group was 10.2 months, compared to 6.9 months in the placebo group (HR, 0.69). Overall survival at 1 year was 43.4% in the nivolumab group vs. 30.1% in the placebo group. The overall response rate was significantly higher in the nivolumab group: 25 patients (11%) had a partial response compared to 1 (1%) in the placebo group. The most frequently reported grade 3 or worse treatment-related adverse events were diarrhea (6 patients [3%] with nivolumab and 2 patients [2%] with placebo) and infusion-related reactions (6 patients [3%] with nivolumab). (Fennell, D. A., et al. (2021). Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): A multicenter, double-blind, randomized, phase 3 trial. Lancet Oncol, 22(11), 1530–1540. Retrieved December 2021 from https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00471-X/fulltext#seccestitle10)Released: December 2021Nursing Drug Handbook© 2021 Wolters KluwerAnticoagulant and Antiplatelet Treatments Associated with Lower Mortality Among Critically Ill COVID-19 PatientsEarly in the pandemic, the mortality rate among critically ill patients was about 50%, but over time, there has been a downward trend in mortality, to between 19% and 40%. Effective treatments for the complications of the viral disease are among the factors responsible for that decline, so quantifying the effectiveness of various treatments used in critically ill patients is essential. A 1-year retrospective cohort study that examined all patients (n = 2,070) admitted to ICUs during the study period in six hospitals affiliated with the Yale-New Haven Health System aimed to identify treatments associated with lower COVID-19 mortality based on multivariable analysis and then to evaluate that finding by propensity score-matching analysis.READ MORE...Treatments studied included any COVID-related pharmacologic or organ support interventions initiated during hospitalization, including antivirals, anticoagulants, antiplatelets, steroids, immunomodulators, immunosuppressants, vasopressors, oxygen therapy delivered through nasal cannula or face mask, bilevel positive airway pressure, continuous positive airway pressure, mechanical ventilation, venovenous hemofiltration, and extracorporeal membrane oxygenation. Potential confounders included in the analysis were known risk factors for COVID, the severity of the acute illness during the first 24 hours after ICU admission, and the various phases of the pandemic. The final analysis included 856 patients (41%) admitted to the ICU during phase 1; 138 (6.7%) during phase 2; 400 (19.3%) during phase 3; and 676 (32.7%) during phase 4. Of the 2,070 patients, 593 died during hospitalization, and 1,477 were discharged alive.The treatments identified as being associated with lower mortality on multivariable analysis included the antiviral atazanavir; the anticoagulants enoxaparin, heparin, and apixaban; the antiplatelet aspirin; famotidine; and oxygen therapy. But after multiple testing corrections, only apixaban and aspirin remained significantly associated with lower mortality.Apixaban treatment was associated with a 52% lower mortality risk. Propensity-score matching analysis with apixaban examined 360 pairs of patients; mortality risk in those treated with apixaban was 27% vs. 37% in the matched cohort not treated with apixaban (hazard ratio [HR], 0.48). Enoxaparin was the anticoagulant of choice for hospitalized COVID patients; in total, 72.7% of patients received enoxaparin, whereas only 19.7% received apixaban. Although multivariable analysis suggested an association between enoxaparin treatment and lower mortality, this result was no longer significant after multiple testing correction. Antiplatelet treatment with aspirin was associated with a 43% lower mortality risk. On propensity-score matching analysis, which examined 473 pairs, mortality risk in those treated with aspirin was 26% vs. 30% in the matched cohort not treated with aspirin (HR, 0.57).Patients admitted to the ICU experienced a much higher risk (30%) of venous thromboembolism than other hospitalized COVID patients (13%). These results suggest taking a more proactive approach toward use of these drugs and in increasing the use of apixaban, to ease the burden of severe COVID disease. (Zhao, X., et al. (2021). Treatments associated with lower mortality among critically ill covid-19 patients: A retrospective cohort study. Anesthesiology, 135, 1076–1090. Retrieved December 2022 from https://pubs.asahq.org/anesthesiology/article/135/6/1076/117698/Treatments-Associated-with-Lower-Mortality-among)Released: December 2021Nursing Drug Handbook© 2021 Wolters Kluwer
Drug News Abstracts - November 2021
Vaccines for COVID-19 Prevention in School-Age ChildrenPediatricians, health officials, and schools are awaiting rollout of COVID-19 vaccines for younger children amid concerns about the effect of the pandemic on children’s mental health and development. As of early November, the Advisory Committee on Immunization Practices (ACIP) has recommended emergency use authorization of a two-dose regimen of 10-mcg apiece, 21 days apart, for the Pfizer-BioNTech mRNA COVID-19 vaccine. The Moderna vaccine could be made available to children and teens by the end of the year.READ MORE...The decision on the Pfizer vaccine was supported by results of a phase 2/3 study that enrolled 3,109 participants ages 5 to 11 who received the vaccine and 1,528 who received placebo. The trial demonstrated efficacy of 90.7%, with 3 COVID cases in the vaccine group and 16 in the placebo group, none of those cases severe.On October 25th, Moderna announced interim data from its phase 2/3 study, KidCOVE, that examined the company’s vaccine candidate against COVID-19 in children ages 6 to 12. KidCOVE showed a robust neutralizing antibody response after two 50-mcg doses. The SARS neutralizing antibody geometric mean ratio comparing the response in the 4,753 participants in the study to that of young adults for the phase 3 COVE study was 1.5, with a seropositive rate of 99.3%.The new vaccines are being made available in an atmosphere of controversy, with a recent poll finding that 25% of parents with school-age children said they would “definitely not” get their child vaccinated. At the same time, other parents are looking to protect their children with vaccines in regions where mask mandates aren’t enforced. As a result of this contentious atmosphere, health care providers are an important source of accurate information. They need to be prepared to counter myths and misconceptions about the vaccine’s risks and benefits. (Walker, M. (2021). FDA panel: High marks for Pfizer’s kid-dose COVID vaccine. MedPage Today. Retrieved November 2021 from https://www.medpagetoday.com/infectiousdisease/covid19vaccine/95278; Moderna. (2021). Moderna announces positive top line data from phase 2/3 study of COVID-19 vaccine in children 6 to 11 years of age. [Press release]. Retrieved November 2021 from https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-top-line-data-phase-23-study-covid-19; Walker, M. (2021). Kids 5-11 can now get Pfizer's COVID vaccine. MedPage Today. Retrieved November 2021 from https://www.medpagetoday.com/infectiousdisease/covid19vaccine/95410)Released: November 2021Nursing Drug Handbook© 2021 Wolters KluwerWeekly Lonapegsomatropin in Growth Hormone DeficiencySince 1987, children with growth hormone (GH) deficiency have been treated with daily injections of somatropin. Although safe, daily injection carries a high treatment burden, which can lead to poor adherence and suboptimal outcomes. Development of a long-acting form of GH aims to create a more convenient treatment, thus improving adherence. Lonapegsomatropin is a once-weekly, long-acting prodrug consisting of the parent drug somatropin, an inert PEG (polyethylene glycol) carrier, and a linker.READ MORE...The phase 3 heiGHt trial of weekly lonapegsomatropin demonstrated superior annualized height velocity (AHV) and statistically greater change in height standard deviation score (SDS) from baseline compared to equivalent doses of daily somatropin. The study, conducted in 73 sites across 15 countries, enrolled 161 prepubertal patients (Tanner stage 1) with GH deficiency, defined as peak GH level ≤10 ng/mL confirmed via two GH stimulation tests. The subjects had a height SDS ≤−2.0, insulin-like growth factor-1 SDS ≤−1.0, and BMI within + 2.0 standard deviation of the mean, as well as bone age ≥6 months behind chronological age. By week 52, 13.8% of all subjects had entered the pubertal transition.The primary endpoint for the study was AHV at week 52; a secondary endpoint was the change from baseline in height SDS. The least squares mean AHV at 52 weeks was 11 cm/year for weekly lonapegsomatropin vs. 10.3 cm/year for daily somatropin. The increase from baseline in least-square mean height SDS was 1.10 SDS for lonapegsomatropin vs. 0.96 SDS for daily somatropin. The study therefore met its goal of demonstrating that the weekly formulation performed at least as well as the daily dose.The AHV range observed was between 5.9 and 18.0 cm/year for lonapegsomatropin and between 4.7 and 16.3 cm/year for somatropin. The treatment difference favoring the weekly formulation started at week 5 and continued throughout the study. There were no serious adverse events related to the study drug, and none led to treatment discontinuation or death. (Thornton, P. S., et al. (2021).Weekly lonapegsomatropin in treatment-naïve children with growth hormone deficiency: The phase 3 heiGHt trial. J Clin Endocrinol Metab, 106(11), 3184–3195. Retrieved November 2021 from https://academic.oup.com/jcem/article/106/11/3184/6323258?searchresult=1)Released: November 2021Nursing Drug Handbook© 2021 Wolters KluwerMitigating Medication Complacency in EpilepsyThe STEP Survey (Seize the Truth of Epilepsy Perceptions), discussed in Neurology Clinical Practices, examined the perceptions of adult patients with epilepsy, along with those of caregivers and health care providers, on treatments for seizuresand treatment decisions. Findings of the surveypoint to potential strategies to mitigate treatment complacency: increased reporting of all seizure occurrences and frequent discussion of and education about possible treatment changes.READ MORE...The self-administered online survey was completed by 400 patients, 200 caregivers, and 258 health care providers. Patient participants were older than age 18, had been diagnosed with epilepsy, and were receiving one or more antiseizure medications. More than half of patients were on their third or more antiseizure medication regimen (58%). In the survey, 61% of patients reported at least 1 seizure with impaired awareness in the past year, 52% reported 1 to 9 seizures, 15% reported 10 to 20 seizures, and 17% reported no seizures in the past year. Eligible caregivers included a patient’s partner (23%), parent (25%), adult child (13%), another family member (27%), and friend (18%). Health care providers surveyed included neurologists (n = 112), epileptologists (n = 96), and nurse practitioners/physician assistants (NPs/PAs; n = 50), who saw at least 20 patients with epilepsy in their practice. The average percentage of patients these providers saw who had focal seizures was 67% for neurologists, 66% for epileptologists, and 55% for NPs/PAs.Treatment complacency was common among all these surveyed groups, despite many patients with uncontrolled seizures. Survey responses point to several factors underlying that complacency. Significantly, according to patients in the survey, they report less than half their seizures (45%) to their health care providers, and caregivers and health care providers aren’t aware of this; caregivers estimate that patients report 83% of their seizures, and health care providers estimate that patients report 73% of their seizures. This disconnect likely contributes to delays in discussions of changes in antiseizure medication treatments.All groups agreed that health care providers were most likely to be the ones to initiate such discussions: 73% of patients, 66% of caregivers, and 77% of health care providers report this. Patients become complacent with their current antiseizure medication regimen, since they are expecting the health care provider to bring the subject up. To close the gap between seizures experienced and those reported, the reasons given by patients for not reporting them—not considering the seizure as serious enough, forgetting, fear of losing their driver’s license, or because health care providers didn’t ask—should be addressed. (Penovich, P. E., et al. (2021). Epilepsy treatment complacency in patients, caregivers, and health care professionals. Neurol Clin Pract, 11(5), 377–384. Retrieved November 2021 from https://cp.neurology.org/content/11/5/377)Released: November 2021Nursing Drug Handbook© 2021 Wolters KluwerSacituzumab Govitecan Effective against Metastatic Triple-Negative Breast CancerFuture Oncology published a summary of findings of the ASCENT study, which demonstrated the effectiveness of the antibody-drug conjugate sacizutumab govitecan against metastatic triple-negative breast cancer. The antibody-drug conjugate is made up of an antibody that targets the human trophoblast cell-surface antigen-2 (Trop-2) coupled to a topoisomerase-1 inhibitor (SV-38). In triple-negative breastcancer, the tumor cells lack expression of estrogen, progesterone, and human epidermal growth factor 2 (HER2) receptors. Because most treatments for breast cancer depend on them being positive for one of these receptors, treating this form of breast cancer is challenging.READ MORE...The randomized, phase 3 ASCENT trial compared the antibody-drug conjugate with single-therapy chemotherapy, the standard treatment for metastatic triple-negative breast cancer. The study included 529 people with metastatic triple-negative breast cancer, all of whom had progressed on two previous chemotherapies and had tumors that could be measured by computed tomography scan or magnetic resonance imaging. They were randomized to Group A (n = 267), receiving IV injections of sacituzumab govitecan on days 1 and 18 of a 21-day cycle, or to Group B (n = 262), chemotherapy determined by the treating health care practitioner: either eribulin (54%), vinorelbine (20%), capecitabine (13%), or gemcitabine (12%).Treatment was continued until disease progression, unacceptable toxic effects, withdrawal from the trial, or death. Those with brain metastases were included in the study only if there was evidence that the tumor had stopped growing for at least 4 weeks. But the primary endpoint was progression-free survival among patients without brain metastases. Progression-free survival in those without brain metastases was 5.6 months in Group A, compared to 1.7 months in Group B; in the total population, progression-free survival was 4.8 months in Group A and 1.7 months in Group B. Overall survival in those without brain metastases was 12.1 months in Group A compared to 6.7 months in Group B; in the total population, it was 11.8 months in Group A and 6.9 months in Group B. Decrease in tumor size was seen in 35% of patients without brain metastases (82/235) in Group A and in 5% of patients (11/233) in Group B; in the total population, decrease in tumor size was seen in 31% of patients (83/267) in Group A and in 4% of patients (11/262) in Group B. The duration of response in patients without brain metastases was 6.3 months in Group A and 3.6 months in Group B; in the overall population, it was 6.3 months in Group A and 3.6 months in Group B.Side effects were seen in 98% of patients receiving sacituzumab govitecan and 86% of those receiving chemotherapy. The most common adverse effects were neutropenia (63% with sacituzumab govitecan and 43% with chemotherapy), diarrhea (59% with sacituzumab govitecan and 12% with chemotherapy), and nausea (57% with sacituzumab govitecan and 26% with chemotherapy). (Bardia, A., et al. (2021). A plain language summary of the ASCENT study: Sacituzumab govitecan for metastatic triple-negative breast cancer. Future Oncol, 17(30), 3911–3924. Retrieved November 2021 from https://www.futuremedicine.com/doi/pdf/10.2217/fon-2021-0868; Bardia, A., et al. (2021). Sacituzumab govitecan in metastatic triple-negative breast cancer. NEJM, 384: 1529–1541. Retrieved November 2021 from https://www.nejm.org/doi/full/10.1056/NEJMoa2028485)Released: November 2021Nursing Drug Handbook© 2021 Wolters Kluwer
Drug News Abstracts - October 2021
Empagliflozin in Heart Failure and Preserved Ejection FractionEMPEROR-Preserved is the first trial to show unequivocal benefit of a medication for treatment of patients with heart failure with preserved ejection fraction (HFpEF). The sodium-glucose transporter-2 (SGLT2) inhibitor empagliflozin lowered the combined risk of cardiovascular (CV) death or hospitalization for heart failure in patients with HFpEF, regardless of the presence or absence of diabetes.READ MORE...The randomized, double-blind, parallel-group, placebo-controlled trial enrolled 5,988 patients with NYHA Class II to IV heart failure and left ventricular ejection fraction (LVEF) >40% (mean age, 72 years; 45% women; mean LVEF, 54%). Nearly half of all patients also had diabetes and nearly half had an eGFR (estimated glomerular filtration rate) of <60 mL/min/1.73 m2. They were randomized to empagliflozin 10 mg once daily (n = 2,997) or to placebo (n = 2,991).SGLT2 inhibition with empagliflozin led to a 21% lower relative risk in the primary composite outcome of death from CV causes and hospitalization for heart failure. The composite outcome occurred in 415 patients (13.8%) in those receiving empagliflozin and in 511 patients (17.1%) in those on placebo. This reduction was mostly attributed to a lower number of hospitalizations for heart failure, with fewer admissions—407 in the empagliflozin arm vs. 514 in the placebo arm (hazard ratio, 0.73). Breaking the composite down into its parts, deaths from CV causes occurred in 219 patients (7.3%) in the empagliflozin arm and in 244 patients (8.2%) in the placebo arm (hazard ratio, 0.91); hospitalization for heart failure occurred in 259 patients (8.6%) in the empagliflozin arm and 352 patients (11.8%) in the placebo arm (hazard ratio, 0.7). The trial also showed a slower decline in renal function over time in those treated with empagliflozin. The rate of decline in eGFR was −1.25 mL/min/1.73 m2/yr in the empagliflozin arm vs. −2.62 mL/min/1.73 m2/yr in the placebo arm.These results are likely to result in a change in clinical practice, as clinicians now have an option for treatment of patients with HFpEF. (Neale, T. (2021). EMPEROR-Preserved: Empagliflozin improves outcomes in HFpEF. Retrieved September 2021 from https://www.tctmd.com/news/emperor-preserved-empagliflozin-improves-outcomes-hfpef; New Engl J Med. 27 August 2021. Empagliflozin in heart failure with preserved ejection fraction. Retrieved September 2021 from https://www.nejm.org/doi/full/10.1056/NEJMoa2107038?query=recirc_curatedRelated_article)Released: October 2021Nursing Drug Handbook© 2021 Wolters KluwerMaternal COVID-19 VaccinationA cohort study published in the American Journal of Obstetrics and Gynecology provided data on maternal antibody generation and suggests that COVID-19 vaccination of women who are pregnant and lactating can confer robust maternal and neonatal immunity against SARS-CoV2 infection. Although the absolute risk of severe COVID-19 is low in women who are pregnant, pregnancy is a risk factor for severe disease. Mothers with severe COVID-19 infections and their neonates are at increased risk for a number of perinatal complications, including cesarean birth, hypertensive disease of pregnancy, venous thromboembolism, preterm birth, low birthweight, and NICU admission. COVID-19 infection in pregnancy is also associated with an increased risk for ICU admission, need for extracorporeal membrane oxygenation, and maternal death.READ MORE...The study enrolled 131 reproductive-age vaccine recipients (84 pregnant, 31 lactating, 16 nonpregnant). Researchers measured titers of SARS-CoV2 spike and reception-binding domain IgA, IgG, and IgM in the recipients’ blood and human milk at the time of the first vaccine dose, at the time of the second dose, 2 to 6 weeks after the second dose, and at delivery (for patients who were pregnant). Umbilical cord titers (n = 10) were assessed at delivery. These titers were then compared with those of women who were pregnant 4 to 12 weeks after a SARS-CoV2 infection (n = 37) by enzyme-linked immunosorbent assay.The mRNA vaccine was highly effective in inducing antibody titers in women who were pregnant (median titer, 5.74) and lactating (median titer, 5.62), results similar to those in women who were not pregnant (median titer, 5.59). Higher levels of antibodies were observed in all women who were vaccinated compared to those of the women who were pregnant who had experienced natural SARS-CoV2 infection. Antibodies were also present in all umbilical cord blood and human milk samples. In particular, a boost in human milk IgG levels was observed, paralleling the boost seen in maternal IgG levels in serum after the second dose. Interestingly, IgA was not increased in the blood or human milk of the women in the study, an unexpected finding, as IgA is the largest component of the immune response in the human milk of women with natural SARS-CoV2 infection.Vaccine-related fever and chills were reported by 32% of women who were pregnant (25/77) and by 50% of women who were not pregnant (8/16) after the second dose. Cumulative symptom score after the first dose was low in all groups, and there were no significant differences between groups in cumulative symptom score after the second dose (median score of 2 for women who were pregnant, 3 for women who were lactating, and 2.5 for women who were not pregnant).Further research in larger populations is needed to support recommendations for vaccine administration in women who are pregnant, as well as providing a greater understanding of vaccine-induced and antibody transfer kinetics across all trimesters. (Pham, A., et al. (2021). Maternal COVID-19, vaccination safety in pregnancy, and evidence of protective immunity. J Allergy Clin Immunol, 148(3), 728–731. Retrieved September 2021 from https://www.jacionline.org/article/S0091-6749(21)01133-7/fulltext; Gray, K. J., et al. (2021). Coronavirus disease 2019 vaccine response in pregnant and lactating women: A cohort study. Am J Obstet Gynecol, 225(3), P303.E1–303.E17. Retrieved September 2021 from https://www.ajog.org/article/S0002-9378(21)00187-3/fulltext#secsectitle0060)Released: October 2021Nursing Drug Handbook© 2021 Wolters KluwerQuadruple Pill for HypertensionA study conducted by the University of Sydney and the George Institute for Global Health showed that a strategy of combining one-quarter doses of four antihypertensive medications into one pill (quadpill) as a first intervention against high blood pressure is more effective than the currently recommended single-drug therapy. This multicenter, double-blind, parallel-group, randomized, phase 3 trial, published in The Lancet and presented at the European Society of Cardiology Conference on August 29th, enrolled 591 patients across 10 Australian centers; participants had high blood pressure (BP) (baseline mean BP: 141/85 mm Hg) and were receiving no therapy or were receiving their first single antihypertensive treatment.READ MORE...The patients were assigned to the quadpill (n = 300), which contained 37.5 mg irbesartan, 1.25 mg amlodipine, 0.625 mg indapamide, and 2.5 mg bisoprolol, or to standard-dose monotherapy (n = 291) with 150-mg irbesartan. Patients who didn’t reach the target BP within 12 weeks could have additional medications added to the regimen, starting with amlodipine at 5 mg. A subgroup continued their randomly assigned treatment for 12 months to assess long-term effects.Blood pressure was brought under control in 76% of participants receiving the quadpill in 12 weeks, compared to 58% in the control group. Mean BP at 12 weeks was 121/71 mm Hg on quadpill therapy versus 127/79 mm Hg on monotherapy; the mean difference in systolic BP was −6.9 mm Hg. The differences in outcome were sustained, with continued better BP control with the quadpill approach at 52 weeks. Mean systolic BP at that time remained lower on quadpill therapy (−7.7 mm Hg); rates of BP control remained higher in the quadpill group (81%) versus controls (62%).Traditional medication treatment for hypertension starts with one antihypertensive and then adds other medications as needed, but this is not always successful; in some regions of the world, as few as 1 in 10 patients have their BP under control. These results could reduce risks of myocardial infarction or stroke by about 20% in areas with access to high levels of specialized treatment; in areas with little or no existing treatment, the benefits could be even greater. (George Institute for Global Public Health. News release. (2021, 30 August). Ground breaking study shows 4 in 1 blood pressure pill is more effective than current treatment. Retrieved September 2021 from https://www.georgeinstitute.org/media-releases/ground-breaking-study-shows-4-in-1-blood-pressure-pill-is-more-effective-than; University of Sydney. Media Release. (2021, 29 August). 4 in 1 blood pressure pill: Safe and much more effective than usual hypertension treatment. Retrieved September 2021 from https://cdn.georgeinstitute.org/sites/default/files/quartet_mr_final.pdf; Chow, C. K., et al. (2021). Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): A phase 3, randomised, double-blind, active-controlled trial. The Lancet, 398(10305), P1043–1052.)Released: October 2021Nursing Drug Handbook© 2021 Wolters KluwerRanibizumab against Retinopathy of PrematurityAnalysis of 2-year outcomes of the RAINBOW extension study, which compares results of intravitreal injection with the vascular endothelial growth factor (VEGF) inhibitor ranibizumab versus laser therapy for treatment of very-low-birthweight infants with retinopathy of prematurity (ROP), were published in Lancet Child and Adolescent Health. Because the retina develops late in fetal development, very premature babies can have incomplete development of the blood vessels needed to provide oxygen to the retina. After birth, blood vessels develop abnormally, causing the vision loss known as ROP. It’s known that an overabundance of VEGF can produce the abnormal blood vessels seen in ROP.READ MORE...Families of the 201 infants who completed the core RAINBOW study were approached for consent to enter an extension study through age 5; 180 infants were enrolled in the extension study, and 153 (85%) were evaluated at age 20 to 28 months for ophthalmic, developmental, and health outcomes, after correcting age for prematurity.No child in this cohort developed new ocular abnormalities (the primary outcome). Structural abnormalities were present in 1 (2%) of the 56 infants in the ranibizumab 0.2-mg group, 1 (2%) of the 51 infants in the ranibizumab 0.1-mg group, and 4 (9%) of 44 infants in the laser therapy group. The odds ratio for structural abnormality was 5.68 for ranibizumab 0.2 mg versus laser therapy, 4.82 for ranibizumab 0.1 mg versus laser therapy, and 1.21 for ranibizumab 0.2 mg versus ranibizumab. 0.1 mg. High myopia, defined as −5 diopters or worse, was less frequent after the 0.2-mg dose of ranibizumab (5/110 eyes [5%]) than with laser therapy (16/82 eyes [20%]); odds ratio, 0.19. In addition, composite vision-related quality of life scores, based on parents’ reports using the Children’s Visual Function Questionnaire, were higher among patients receiving 0.2 mg ranibizumab (mean score, 84) compared with those receiving laser therapy (mean score, 77). Developmental scores, as assessed by the Mullen Scales of Early Learning, were similar across the three groups. (Marlow, N., et al. (2021). 2-year outcomes of ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW extension study): Prospective follow-up of an open label, randomised controlled trial. Lancet Child Adolesc Health. Advanced online publication. Retrieved September 2021 from https://www.thelancet.com/pdfs/journals/lanchi/PIIS2352-4642(21)00195-4.pdf)Released: October 2021Nursing Drug Handbook© 2021 Wolters Kluwer
Drug News Abstracts - September 2021
COVID Boosters Supported by CDC, FauciIn a White House press briefing, U.S. health officials laid out the case for a scientific rationale for administering a third dose of the COVID-19 mRNA vaccines for all U.S. adults. CDC Director Rochelle Walensky presented evidence that showed that vaccine effectiveness has been decreasing over time against both symptomatic and asymptomatic infections, although protection against severe disease, hospitalizations, and death remains relatively high. Dr. Walensky presented evidence from several studies published in MMWR and by the Mayo Clinic (posted on medRxiv).READ MORE...MMWR data from New York showed a decline in vaccine effectiveness against infection from May 3 to July 25, from 91.7% to 79.8%. Overall age-adjusted vaccine effectiveness against hospitalization was relatively stable: from 91.9% to 95.3%. The total of new cases was 9,675 among fully vaccinated adults, compared with 38,505 among unvaccinated persons (rate of 1.31 per 1,000 person-days vs.10.69 per 1,000 person-days).Data from the Mayo Clinic found a similar decrease in vaccine effectiveness in Minnesota. Moderna vaccine effectiveness fell from 86% earlier in the year to 76% during July, and Pfizer vaccine effectiveness fell from 76% to 42% over the same time. The analysis also found that both mRNA vaccines were effective at protecting against COVID-associated hospitalizations (91.6% for Moderna, 85% for Pfizer) and ICU admissions (93.3% for Moderna, 87% for Pfizer), with no deaths in either cohort.New nursing home data reported in MMWR also showed a reduction in protection against infection, from 78% in March to 53% by August 1. These results may reflect the effect of the greater transmissibility of the Delta variant along with demonstrating waning immunity: adjusted effectiveness against infection in the pre-Delta period (March 1 to May 9) was 74.7%, fell to 67.5% in the intermediate period (May 10 to June 20), and to 53.1% during the Delta-dominant period (June 21 to August 1).At the briefing, Anthony Fauci provided the immunologic evidence supporting booster shots. A paper published in Science showed that antibody levels peaked 43 days after the second dose of Moderna, but fell by 209 days after vaccination. Additional research demonstrated that a serum neutralizing titer of 1:100 is needed to produce a vaccine efficacy rate of 91%. Dr. Fauci believes that the booster shot should increase antibody titers by tenfold and that such higher antibody levels are likely to be necessary to protect against the Delta variant. (Fiore, K. (2021). The science supporting the U.S. case for COVID boosters. MedPage Today. Retrieved August 2021 from https://www.medpagetoday.com/infectiousdisease/covid19vaccine)Released: September 2021Nursing Drug Handbook© 2021 Wolters KluwerTriple-Drug Therapy Effective for Cystic FibrosisUse of a three-drug combination improved lung functionand sweatchloride concentration relative to an active control in a subclass of patients with cystic fibrosis.In a phase 3, double-blind, randomized, active-control trial, the three-drug combination ivacaftor–tezacaftor–elexacaftor was tested as treatment for cystic fibrosis in patients who had Phe508del-gating or Phe508del-residual function genotypes. In cystic fibrosis, deficiencies in the cystic fibrosis transmembrane conductance regulator (CFTR) proteins manifests in progressive respiratory impairment, exocrine pancreatic insufficiency, hepatobiliary disease, and abnormal sweat composition. Cystic fibrosis results from biallelic mutations in the CFTR gene, among them processing mutations, which reduce the quantity of CFTR protein on the cell surface; channel-gating defects, which limit anion transport; and residual function mutations, which result in lesser impairment of CFTR protein activity. Ivacaftor is a CFTR potentiator that augments gating of mutant CFTR proteins, tezacaftor is a CFTR corrector that acts to ease the defects of CFTR processing and cell-surface trafficking intrinsic to Phe508del, andelexacaftor is a CFTR corrector with a mechanism of action complementary to tezacaftor.READ MORE...The trial aimed to determine whether additional clinical benefit could be derived from that complementarity. The trial enrolled 258 patients and randomized them to receive the three-drug combination at 200 mg/day (n = 132) or to one of two active control regimens (n = 126): ivacaftor 150 mg b.i.d. or ivacaftor 150 mg b.i.d. and tezacaftor 100 mg/day, based on the patients’ specific genotype and approvals in their country. At baseline, the mean sweat chloride concentration was 58 mmol/L; the mean forced expiratory volume in 1 second (FEV1) was 67% to 68%, with about half in the 40% to 70% range and the rest at 70% to 90%; and the mean score on the Cystic Fibrosis Questionnaire Revised (CFQ-R) respiratory domain was 77.The mean absolute change in percentage of predicted FEV1 from baseline through week 8 was 3.7 percentage points (range, 2.8 to 4.6) in patients receiving the three-drug combination and 0.2 percentage points (range, –0.7 to 1.1) in patients on active control, reflecting a between-group difference of 3.5 percentage points. The mean absolute change in sweat chloride concentration from baseline through week 8 with the three-drug combination was –22.3 mmol/L (range, –24.5 to –20.2 mmol/L) and with active controls was 0.7 mmol/L (range, –1.4 to –2.8 mmol/L), a between-group difference of –23.1 mmol/L. Change from baseline in scores on the CFQ-R respiratory domain was 10.3 points (range, 8.0 to 12.7) on the three-drug combination and 1.6 points (range, –0.8 to 4.1 points) on active control, reflecting a between-group difference of 8.7 points.Two-thirds of patients experienced an adverse event, but most were mild or moderate in severity and resolved during the trial. Serious events were reported in 5 patients (3.8%) in the treatment group and 11 patients (8.7%) in the control group. (Gever, J. (2021). Three drugs better than two (or one) in cystic fibrosis. MedPage Today. Retrieved August 2021 from https://www.medpagetoday.com/pulmonology/cysticfibrosis; Barry, P. J., et al. (2021). Triple therapy for cystic fibrosis Phe508del–gating and –residual function genotypes. New Engl J Med 385, 815–825.)Released: September 2021Nursing Drug Handbook© 2021 Wolters KluwerAtopegant: An Effective Oral Migraine PreventiveOnce-daily oral treatment with atopegant, a small-molecule, calcitonin gene-related peptide (CGRP) receptor antagonist, was effective in reducing the number of migraine days and headache days over 12 weeks in patients with episodic migraine. These are the findings of ADVANCE, a phase 3multinational, randomized, double-blind, parallel-group, placebo-controlled trial that examined three dosage strengths of atopegant for prevention of migraine.READ MORE...In the trial, adults with 4 to 14 migraine days/month were randomly assigned to receive once-daily doses of 10 mg, 30 mg, or 60 mg of atopegant or to placebo for 12 weeks. Patient characteristics were similar across all groups: mean age, 41.6 years; 88% female and 83.4% white; with a mean BMI of 30.6. Overall, patients reported an average of 7.4 migraine days/month over the previous 3 months; at screening, 99.3% reported current use of medications to treat migraine attacks, and 70.3% reported having previously used a preventive medication for migraine.After screening and randomization, patients returned to the clinic five times during the double-blind 12-week period, with another visit at 16 weeks. The protocol was amended due to the COVID-19 pandemic to allow remote visits, with the final visit being conducted remotely for all participants. In an electronic diary, patients recorded headache duration, the clinical features of the headache (pain severity, location, and the effect of routine physical activity on migraine), nonheadache-associated symptoms (nausea/vomiting, photophobia, phonophobia, aura), and any medications used to treat the migraine attacks.Analysis included 873 patients: 214 in the 10-mg group, 223 in the 30-mg group, 222 in the 60-mg group, and 214 in the placebo group. Oral atopegant at any of the doses resulted in significantly greater reductions in the number of migraine days per month versus placebo. The change from baseline was –3.7 days for the 10-mg dose, –3.9 days for the 30-mg dose, and –4.2 days for the 60-mg dose, compared to –2.5 days with placebo. The differences with placebo in secondary outcomes were also significant: The change from baseline in mean number of headache days/month was –3.9 days for the 10-mg dose, –4.0 days for the 30-mg dose, and –4.2 days for the 60-mg dose, compared to –2.5 days with placebo. The change in the mean number of days of medication use to treat migraine was –3.7 days for the 10-mg dose, –3.9 days for the 30-mg dose, and –3.9 days for the 60-mg dose, compared to –2.4 days with placebo. The percentage of participants with a reduction of at least 50% in the 3-month average of migraine days/month has been recommended as a particularly relevant endpoint in controlled trials of preventive treatments for migraine; in this trial, this goal was reached at all three dosage levels: 55.6% of those receiving the 10-mg dose, 58.7% of those receiving the 30-mg dose, and 60.8% of those receiving the 60-mg dose, compared to 29.0% of those receiving placebo.Adverse events were reported in 486/902 participants (53.9%) with similar frequency across all groups. The most common adverse events were constipation, nausea, and upper respiratory infections. Serious adverse events were reported in 4 participants, 2 on the 10-mg dose and 2 on placebo. Because of potential hepatotoxicity, elevated ALT or AST levels at least three times the upper level of normal were evaluated throughout the trial. These elevated levels were found in 2 participants in the 10-mg group, 2 in the 30-mg group, 1 in the 60-mg group, and 4 in the placebo group.Previous studies have shown an association between CGRP blockade and decreased GI motility, so continued monitoring for constipation, as well as measuring for hepatotoxicity, is appropriate going forward. In addition, longer, larger trials are necessary to examine the long-term safety of once-daily atopegant as a migraine preventative; a 52-week trial is currently underway. (Ailani, J., et al. (2021). Atogepant for the preventive treatment of migraine. New Engl J Med; 385: 695–706.)Released: September 2021Nursing Drug Handbook© 2021 Wolters Kluwer
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