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Drug News Abstracts - June 2024

Analysis of Self-Administered Aspirin Post-Chest Pain to Prevent Cardiovascular Mortality

According to the American Heart Association, someone experiences an acute myocardial infarction (AMI) in the United States every 40 seconds, making it a leading cause of mortality. However, a significant number of AMI deaths occur outside the hospital, with delayed access to medical care being a contributing factor. The International Study of Infarct Survival sought to analyze the potential benefits and risks of self-administering aspirin within 4 hours of experiencing severe chest pain to reduce mortality post-AMI.

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Dequalinium as Potential Treatment for Bacterial Vaginosis

Bacterial vaginosis (BV), a common and recurrent vaginal infection in females of reproductive age, is typically treated with antibiotics, like metronidazole and clindamycin. However, their adverse effects and risk of antibiotic resistance necessitate alternative treatments. A recent study evaluated the efficacy of dequalinium chloride, an antiseptic with broad-spectrum activity against various microorganisms, as a potential nonantibiotic treatment for BV.

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Progestogen Versus Combined Oral Contraceptive for Endometriosis Pain

Endometriosis, affecting up to 1-in-10 women of reproductive age, involves the growth of endometrial-like tissue outside the uterus, leading to severe pelvic pain and infertility. Surgical treatment is common, but recurrence rates are high, with many women undergoing multiple operations. Hormonal treatments, like the combined oral contraceptive pill (COCP) and progestogens, are recommended postsurgery, but it's uncertain which is more effective in preventing pain recurrence.

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Perioperative Nivolumab for Non-Small-Cell Lung Cancer

Nivolumab, an antibody targeting programmed death-1, in combination with chemotherapy is standard neoadjuvant treatment for patients with resectable non-small-cell lung cancer (NSCLC). Studies, including the landmark CheckMate 816 trial, showed significant improvements in event-free survival and pathologic complete response with this combination compared to chemotherapy alone. Based on these results, researchers questioned whether a perioperative approach, combining neoadjuvant therapy with nivolumab, followed by surgery and adjuvant therapy, could reduce disease relapse rates, and enhance clinical outcomes by bolstering antitumor immunity.

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Drug News Abstracts Archive

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
Drug News Abstracts - August 2021
Combination of Atezolizumab and Bevacizumab Effective in Peritoneal MesotheliomaCombination treatment with atezolizumab and bevacizumab was well-tolerated and led to strong, durable responses in patients with malignant peritoneal mesothelioma whose disease progressed with platinum-pemetrexed chemotherapy or were intolerant to that prior therapy. A phase 2 single-center study conducted at the University of Texas MD Anderson Cancer Center and published in Cancer Discovery examined results in patients with this rare but aggressive disease, a cancer in the lining of the abdomen. Malignant peritoneal mesothelioma has an annual incidence of 0.11/100,000 (300 to 500 Americans each year) and a 5-year survival rate lower than 20%.READ MORE...Malignant peritoneal mesothelioma is usually treated following recommendations developed for pleural mesothelioma, with first-line treatment with platinum-based/pemetrexed chemotherapy, but there are no approved treatments if that fails. The single-center study evaluated the combination of atezolizumab and bevacizumab as treatment for various advanced cancers. Atezolizumab is an immune checkpoint inhibitor that targets PD-L1, and bevacizumab is a VEGF inhibitor that slows the growth of new blood vessels and therefore tumor growth. The malignant peritoneal mesothelioma cohort included 20 participants, median age 60. Mean follow-up was 23.5 months. These patients had experienced disease progression at a median of 8.3 months with prior platinum-pemetrexed therapy.The confirmed objective response rate to treatment with this combination, as measured by RECIST (Response Evaluation Criteria in Solid Tumors) was 40% (8/20 patients). Median duration of response was 12.8 months, and responses were ongoing at cutoff in 6 patients. Median progression-free survival was 17.6 months, and the 1-year progression-free survival rate was 61%. Overall survival rate at 1 year was 85%. Disease control per RECIST was 95% (19/20) at 12 weeks, and 85% (17/20) at 18 weeks. Responses occurred no matter the tumor mutational burden or PD-L1 expression status. Treatment was well-tolerated; grade 3 adverse events occurred in 10 patients, most commonly hypertension and anemia. No grade 4 or 5 events occurred.These results address the challenges of caring for advanced forms of this orphan disease. Further studies that enroll more patients and that examine this combination as front-line treatment or as preoperative treatment are needed. (University of Texas MD Anderson Cancer Center. (2021). Drug combination shows meaningful responses for malignant peritoneal mesothelioma patients. ScienceDaily. Retrieved August 2021 from https://www.sciencedaily.com/releases/2021/07/210714110422.htm; Raghav, K., et al. (2021). Efficacy, safety and biomarker analysis of combined PD-L1 (atezolizumab) and VEGF (bevacizumab) blockade in advanced malignant peritoneal mesothelioma. Cancer Discovery: American Association for Cancer Research. Advance online publication. Retrieved August 2021 from https://cancerdiscovery.aacrjournals.org/content/candisc/early/2021/07/01/2159-8290.CD-21-0331.full.pdf)Released: August 2021Nursing Drug Handbook© 2021 Wolters KluwerA Booster COVID Shot May Produce Antibody Response in Kidney Transplant RecipientsA French study offers evidence that a third dose of a COVID-19 mRNA vaccine can be beneficial to transplant recipients who failed to maintain sufficient antibody responses to the first two doses. Studies have reported low seroconversion rates (58%) after the second dose insolid organ transplant recipients. In April 2021, the French National Authority for Health recommended administration of a third dose of the mRNA vaccines in immunosuppressed patients who hadn’t responded after two doses.READ MORE...The single-center study enrolled 159 kidney transplant recipients at the outpatient Kidney Transplantation Department of Strasbourg University Hospital in the first half of 2021. Median age was 57.6 years, 61.6% were men, and median time from transplantation was 5.3 years. More than half were receiving tacrolimus or mycophenolate mofetil and steroids as immunosuppressive maintenance therapy. All had a negative history of COVID-19 and, though they had been vaccinated, had SARS-CoV2 antispike IgG levels of less than 50 AU/mL. Of these patients, 95 (59.7%) had no antibody response at all, with titers less than 6.8 AU/mL, and 64 (40.3%) had a response below the positivity level, with titers between 6.8 and 49.9 AU/mL.Patients received a third dose of the Moderna mRNA vaccine about 51 days after the second dose; serologic response was measured a median of 28 days later. That measure demonstrated that 78 patients (49%) did have an antibody response greater than 50 AU/mL. Those who had a weak response after the second dose were more likely than those with no response to reach this level: 81.3% vs. 27.4%, respectively. Those who were taking tacrolimus, mycophenolate mofetil, and steroids for immunosuppression were less likely to develop antibodies than those treated with other regimens: 35% vs. 63%, respectively. No serious adverse events were reported after the third dose. (Benotmane, I., et al. (2021). Antibody response after a third dose of the mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients with minimal serologic response to 2 doses. JAMA. Retrieved August 2021 from https://jamanetwork.com/journals/jama/fullarticle/2782538;Monaco, K. (2021). Case mounts for COVID vaccine boosters in kidney transplant recipients. MedPage Today. Retrieved August 2021 from https://www.medpagetoday.com/infectiousdisease/covid19vaccine)Released: August 2021Nursing Drug Handbook© 2021 Wolters KluwerTofacitinib Improves Inflammatory Bowel Disease SymptomsTreatment with tofacitinib improved results versus placebo on all items on an Inflammatory Bowel Disease Questionnaire (IBDQ) in patients with ulcerative colitis, reflecting improvements in health-related quality of life, with the greatest benefits reported in bowel symptoms.The 8-week, randomized, double-blind, phase 3 OCTAVE Induction 1 and 2 studies examined the oral, small-molecule Janus kinase inhibitor as treatment of ulcerative colitis. The objective of this analysis was to enrich understanding of the treatment effect of tofacitinib versus placebo on individual items in the IBDQ at week 4 and week 8.READ MORE...Patients in the study had moderately to severely active ulcerative colitis with a confirmed diagnosis of at least 4 months, and treatment failure or intolerance to oral or IV glucocorticoids, azathioprine, mercaptopurine, infliximab, or adalimumab. The pooled OCTAVE 1 and 2 studies randomized 234 patients to placebo and 905 to tofacitinib. The patients self-administered the IBDQ questionnaire at baseline, week 4, and week 8, with higher scores indicating better health-related quality of life. Significant improvements were observed in all 32 IBDQ items from baseline, grouped into four domains—bowel symptoms, systemic symptoms, emotional function, and social function. The largest differences reported in the bowel symptom domains were in loose bowel movements (1.1-point improvements at weeks 4 and 6) and rectal bleeding (1.1-point improvement at week 8). The largest differences reported in the systemic symptoms domain were reported in improvements in sleep (0.8-point improvement at week 4 and 0.9-point improvement at week 8). The largest improvements reported in the emotional function domain were seen in “fear of not finding a restroom” (0.6-point improvement at week 4 and 0.8-point improvement at week 8) and in embarrassment and anger (both improved by 0.6 points at week 4). The largest improvements reported in the social function domain were seen in avoidance of attendance at events (0.8-point improvement at week 4 and 1-point improvement at week 8) and in “difficulty doing leisure/sports” (1.0-point improvement at week 8).Larger effect sizes (above 0.65 points) were seen, therefore, in two bowel symptoms (loose bowel movements and rectal bleeding), and small or medium effect sizes in all other components of the IBDQ except for “problems with maintaining weight” and “lack of understanding from others.” The effect sizes were mostly unchanged between week 4 and week 8 for many items, indicating that most of the treatment effect was observed early as the patient’s inflammatory burden and symptoms improved. (Dubinsky, M. C., et al. (2020). Tofacitinib in patients with ulcerative colitis: Inflammatory Bowel Disease Questionnaire items in phase 3 randomized controlled induction studies. Inflammatory Bowel Dis; 27(7): 983–993. Retrieved August 2021 from https://academic.oup.com/ibdjournal/article/27/7/983/5892619)Released: August 2021Nursing Drug Handbook© 2021 Wolters KluwerAntidepressants May Improve Outcomes in People with Diabetes and DepressionA new study published in the Journal of Clinical Endocrinology and Metabolism suggests that patients with both diabetes and depression who take antidepressants have a lower riskof death and of serious diabetes complications. The nationwide retrospective cohort study identified 36,276 patients with depression and diabetes using Taiwan’s universal health insurance database.The majority of the study population was female and between ages 45 and 64. The study classified antidepressant treatment patterns within a 6-month window as none, poor, partial, and regular use. Macrovascular and microvascular diabetes complications and all-cause mortality were the main outcomes of the study.READ MORE...Patients with greater adherence to antidepressants appeared to experience fewer complications and a lower risk of mortality when compared to those with suboptimal use of their antidepressant medications. Overall, 9,670 patients developed macrovascular diabetes complications, 6,837 patients developed microvascular diabetes complications, and 3,820 patients died. Compared with poor use, regular use of oral antidepressants was associated with an 8% decreased risk for macrovascular complications (adjusted hazard ratio [HR], 0.92) and a 14% decreased risk for all-cause mortality (adjusted HR, 0.86). It was not associated with changes in risk of microvascular complications.On further analysis, regular use of SSRIs was associated with a 17% decreased risk for macrovascular complications (adjusted HR, 0.83) and a 25% reduced risk for all-cause mortality (adjusted HR, 0.75). Regular use of tetracyclic or tricyclic antidepressants was associated with a 22% decreased risk for all-cause mortality (adjusted HR, 0.78). Regular use of benzodiazepines, on the other hand, showed no association with diabetic outcomes.Patients with diabetes are at higher risk for depression, and depression worsens diabetes complications related to stress, body weight changes, and lack of exercise. This makes these patients more likely to develop diabetes complications, including heart and kidney disease, stroke, and eye and foot problems. Controlling comorbid depression is therefore important in these patients. Clinicians should encourage antidepressant treatment adherence among patients with diabetes and depression. (The Endocrine Society. (2021). Antidepressants may improve outcomes in people with diabetes and depression. ScienceDaily. Retrieved August 2021 from https://www.sciencedaily.com/releases/2021/07/210714131927.htm; Wu, C-S., et al. (2021). Associations between Antidepressant Use and Advanced Diabetes Outcomes in Patients with Depression and Diabetes Mellitus. J Clin Epidemiol Metab, Article dgab443. Retrieved August 2021 from https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgab443/6321009?redirectedFrom=fulltext)Released: August 2021Nursing Drug Handbook© 2021 Wolters Kluwer
Drug News Abstracts - July 2021
Research into Antivirals for Outpatient Treatment of COVID-19Antiviral treatment of early COVID-19—before hospitalization—is needed to prevent progression of disease, the generation of variants, and secondary transmission of the virus. An article in Clinical Infectious Diseases discusses the current outpatient treatment landscape, outlining the difficulties in treating this disease, and describing ongoing research into antivirals.READ MORE...The ability to provide early antiviral treatment to prevent progression of the disease is hampered by the difficulties in detecting COVID-19 and in predicting which infected individuals will become symptomatic. This remains a major challenge to management of the pandemic, as some persons who appear to have few risk factors have been known to develop serious, even fatal, infections.The FDA has issued emergency use authorization for two monoclonal antibody (MAb) combinations—casirivimab + imdevimab and bamlanivimab + etesevimab—for patients with mild to moderate COVID-19. Research shows that these treatments are most effective in those patients who are slow to mount a SARS-CoV2-specific immune response. When given early in the course of symptomatic infection, these MAb regimens demonstrate both reductions in the SARS-CoV2 detected on polymerase chain reaction and in the risk of more severe illness. But timely use of MAbs is difficult, given the problems with obtaining testing results in many populations.The IV administration route for MAbs also presents a barrier to their use in outpatients. Research is ongoing into developing agents that can be administered by more user-friendly routes, including oral and inhaled agents. The Centers for Disease Control and Prevention’s ACTIV-2 study is part of ongoing efforts to develop antiviral agents that are easier to administer, and thus can be used in the outpatient setting; these agents include:· AZD8895 and AZD1061, a MAb combination that is in phase 2 studies and is being examined in both IV and IM formulations· Camostat mesylate, an oral serine protease inhibitor that blocks entry of the virus into cells· Interferon beta is an inhaled formulation delivered by nebulizer that is also in phase 2.A final emerging consideration in development of antiviral treatments for early COVID-19 infection is any interaction between these treatments and the vaccines. COVID-19 in a person who is fully vaccinated suggests either an inadequate immune response or infection with a variant. The struggle to contain this outbreak continues. (Cohen, M. S., et al. (2021). Outpatient treatment of SARS-CoV-2 infection to prevent COVID-19 progression. Clin Infect Dis. Advance online publication. Retrieved June 2021 from https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab494/6287650)Released: July 2021Nursing Drug Handbook© 2021 Wolters KluwerRisks of Discontinuing Statins in Older PatientsOlder people are at risk for polypharmacy, and increasingly there have been calls for deprescribing to simplify medication regimens because of fears of negative clinical consequences, including cognitive impairment and drug-drug interactions, arising from such use. But deprescribing carries risks of its own. A population-based observational study demonstrated that when older patients who are taking numerous drugs for multiple conditions stop taking statins, they are at higher risk for heart failure or other CV events and of death compared to patients who continue statins.READ MORE...The study collected data from an Italian health care utilization database and included 24,097 patients who were taking statins, antihypertensives, antidiabetic agents, and antiplatelets. Using the Multisource Comorbidity Score (MCS), an index of clinical status based on the presence of conditions derived from inpatient diagnostic information and outpatient drug prescriptions, 11.7% of these patients were considered to have a “severe” clinical profile. After approximately 2 ½ years of follow-up, 9,204 patients (31.7%) discontinued taking statins, including 5,819 patients who stopped statins before discontinuing other drug therapy. The researchers matched 4,010 patients who stopped statins alone (discontinuing group) with 4,010 patients who maintained adherence to all four drug classes (maintenance group) and then followed both groups to estimate the hazard of negative outcomes. The discontinuing group was 60% men, with a mean age of 76.5 years, and 12.6% had MCS scores of 4 to 5. In the maintenance group, 61.7% were men, with a mean age of 76.1 years, and 12.6% had MCS scores of 4 to 5. Compared with the maintenance group, the discontinuing group had an increased risk of hospital admissions for heart failure or any CV outcome, death from any cause, and emergency admissions for any cause. After a mean follow-up of 20.6 months and 20.4 months, respectively, for patients who discontinued and maintained statins, the results were as follows:· Hospital admissions for heart failure: 408 vs. 337 events, with an incidence rate of 64 per 1,000 patient-years vs. 51.5 per 1,000 patient-years· Hospital admissions for ischemic heart disease: 439 vs. 413 events, with an incidence rate of 69.7 per 1,000 patient-years vs. 64.6 per 1,000 patient-years· Deaths from any cause: 528 vs. 463 events, with an incidence rate of 77.5 per 1,000 patient-years vs. 67.4 per 1,000 patient-years· Emergency department (ED) admissions for any cause: 2,209 vs. 2,055 events, with an incidence rate of 506.2 per 1,000 patient-years vs. 449.8 per 1,000 patient-years.Stopping statins was associated with a 12% higher risk of ED admissions for any cause, a 24% higher risk of heart failure, and a 15% higher risk of death from any cause. But the simplification of the patient’s medication regimen didn’t generate a significant reduction in ED access for neurologic causes, a proxy for episodes of delirium.This study was limited by its design, in which adherence to medication was determined by prescriptions rather than actual use. In addition, researchers didn’t know why prescriptions were discontinued. It’s possible that the patients who discontinued were not following other health guidelines or effectively managing their CV risk factors. But some discontinuations could be due to adverse drug effects, perceived adverse effects, or to a physician’s judgment that the patient is low risk. Further research is necessary to understand these findings. (O’Riordan, M. (2021). Stopping statins ups CVD and mortality risks in pill-burdened seniors. TCTMD. Retrieved June 2021 from https://www.tctmd.com/news/stopping-statins-ups-cvd-and-mortality-risks-pill-burdened-seniors; Rea, F., et al. (2021). Cardiovascular outcomes and mortality associated with discontinuing statins in older patients receiving polypharmacy. JAMA Netw Open. 4(6), Article e2113186. Retrieved June 2021 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780952)Released: July 2021Nursing Drug Handbook© 2021 Wolters KluwerAcute Medication Overuse in Patients with MigraineAcute medication overuse (AMO) is common in people with migraine and is associated with risk of disease progression from episodic migraine to chronic migraine. Analysis of data from the CaMEO study (Chronic Migraine Epidemiology and Outcomes) published in Neurology Clinical Practice sought to estimate the frequency of AMO and to characterize the type of medications involved.READ MORE...CaMEO was a cross-sectional, longitudinal web-based survey of the U.S. population. From September 2012 to November 2013, data was collected on the clinical course of migraine, family burden, barriers to care, migraine type, and comorbidities. In patients who met criteria for migraine consistent with the International Classification for Headache Disorders (ICHD-3), this analysis evaluated the types of medications used to treat or prevent migraine and the frequency of their use, comorbidities, and the number of emergency department (ED) and urgent care visits.Medication overuse headache (MOH) is defined by the ICHD-3 as headache occurring at least 15 days per month in individuals with preexisting headache disorder and regular overuse of acute medications for longer than 3 months. AMO in the ICHD-3 refers to taking medications for at least 10 days per month (or at least 15 days per month for simple analgesics). Of 16,789 CaMEO respondents with migraine, 2,975 (17.7%) met criteria for AMO; about 67.9% reported fewer than 15 monthly headache days and 49% reported fewer than 10 monthly headache days; this finding suggests that these respondents are taking their antimigraine medications on days when they don’t have a headache (perhaps in anticipation of a headache), or were taking multiple drugs to treat each headache, thus meeting the criteria for AMO.The majority of respondents met the criteria for at least one medication class (2,753/2,975 [92.5%]), including at least 15 days’ use for simple analgesics like naproxen sodium, aspirin, ibuprofen, acetaminophen, and prescription, or at least 10 days’ use for ergotamines, triptans, opioids, or combination analgesics. A much smaller group met the criteria for AMO when their use of multiple medications was considered (222/2,975 [7.4%]); use of two or more simple analgesics cumulatively, but not any single medication, for more than 15 days; or use of two or more ergotamines, triptans, opioids, or combination analgesics, but not any single medication, for more than 10 days. Of the respondents with migraine, 14,936 (89%) reported using any acute medication; use of any OTC medication for headache was reported by 14,279 (85%) and of prescription medications was reported by 4,902 (29.2%).Those with AMO were more likely than other respondents to have moderate to severe depression, anxiety, headache-related disability, and burden of disease between attacks. They also reported a higher incidence of ED and urgent care visits related to their headaches within the past 6 months. These findings illustrate the need for comprehensive migraine treatment plans that include improved acute treatment options as well as guideline-based preventive treatments, which include both nonpharmacologic and pharmacologic methods, to reduce frequency of AMO and the associated burden from possible MOH. (Schwedt, T. J., et al. (2021). Medication overuse and headache burden: Results from the CaMEO study. Neurol Clin Pract; 11(3): 216–222. Retrieved June 2021 from https://cp.neurology.org/content/11/3/216)Released: July 2021Nursing Drug Handbook© 2021 Wolters KluwerSotorasib Has Anticancer Activity in NSCLCKRAS is one of the most highly mutated genes in human cancers, found in 32% of lung adenocarcinomas. The KRASG12C variation is the most common variant in non–small-cell lung cancer (NSCLC), with a prevalence of 13%. The New England Journal of Medicine reported results from the phase 2 CodeBreak100 trial, a multicenter, single-group, open-label trial that evaluated the efficacy and safety of the highly selective irreversible KRASG12C inhibitor sotorasib in patients with KRASG12C mutated advanced NSCLC.READ MORE...The study enrolled 126 patients, of whom 124 had measurable disease at baseline and so were evaluated for their response to sotorasib. The patents were older than age 18, had locally advanced or metastatic NSCLC with the KRASG12C mutation, with disease progression after receipt of anti-PD-1 or anti-PD-L1 immunotherapy or platinum-based combination chemotherapy, ECOG performance status scale of 0 to 1, and measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients were enrolled from August 2019 to February 2020 and received at least one dose of sotorasib (960 mg/day PO).Median duration of treatment was 5.5 months. As of the data cutoff date, 103 patients (81.7%) had discontinued treatment with sotorasib, 83 due to disease progression and 11 due to adverse effects. Dose reduction was seen in 26 patients (20.6%). Objective tumor response was observed in 46 patients (37.1%), 4 (3.2%) with a complete response and 42 (33.9%) with a partial response. Among those 46 patients, median time to response was 1.4 months and median duration of response was 11 months. As of data cutoff, 16 patients (34.7%) were continuing to receive sotorasib without disease progression. Median progression-free survival was 6.8 months, and median overall survival was 12.5 months. Treatment-related adverse events occurred in 88 patients (69.8%), including grade 3 events in 25 patients (19.8%) and grade 4 events in 1 patient (0.8%).Further analysis evaluated the potential association between response to sotorasib therapy and these variables:· baseline PD-L1 expression (86 patients assessed): objective response and tumor shrinkage were observed in 48% of patients in the PD-L1-negative group and in 42% of those in the PD-L1-positive group· tumor mutational burden (84 patients assessed: objective response and tumor shrinkage were observed in 42% of patients with low tumor mutational burden and 40% of patients with high tumor mutational burden· co-occurring genomic alterations (104 patients assessed): objective response was seen in 50% of patients with mutated STK11 and wild-type KEAP1, in 23% of those with mutations in both KEAP1 and STK11, and in 14% of those with mutated KEAP1 and wild-type STK11.These data provide further evidence in support of the use of sotorasib in this population. A phase 3 trial comparing sotorasib to docetaxel in patients with previously treated, locally advanced, unresectable or metastatic NSCLC with KRASG12C mutation is underway. (Rosen, N. (2021). Finally, effective inhibitors of mutant KRAS. New Engl J Med; 384: 2447–2449. Retrieved June 2021 from https://www.nejm.org/doi/full/10.1056/NEJMe2107884; Skoulidis, F., et al. (2021). Sotorasib for lung cancers with KRAS p.G12C mutation. New Engl J Med; 384: 2371–2381. Retrieved June 2021 from https://www.nejm.org/doi/full/10.1056/NEJMoa2103695?query=featured_home)Released: July 2021Nursing Drug Handbook© 2021 Wolters Kluwer
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