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Drug News Abstracts - April 2024

Great Variation in Opioid Prescribing for High-Risk Infants in U.S. Hospitals

A study of nearly 150,000 infants admitted to 47 children's hospitals in the United States found that most of the high-risk infants received opioids during hospitalization, with wide variations across U.S. regions and between hospitals. It demonstrated significant hospital-level variations in opioid and methadone exposure and in the cumulative days of opioid use.

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Leptin Increase during Dexamethasone Use in Pediatric Acute Lymphoblastic Leukemia

High-dose dexamethasone, a common component of maintenance treatment in children with acute lymphoblastic leukemia (ALL), induces well-known side effects, including dyslipidemia, increased appetite, and consequent unhealthy eating behaviors, as well as increased fatigue and sleep problems. A study conducted within the Dexa Days-2 study, a Dutch national randomized controlled trial that analyzes dexamethasone-induced neurobehavioral problems in ALL patients, aimed to determine the influence of the 5-day dexamethasone course on changes in leptin, as well as fat mass, body mass index (BMI), hunger, sleep, and fatigue and to explore associations between these variables.

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Nirsevimab 90% Effective Against Hospitalization for RSV

Respiratory syncytial virus (RSV) is the leading cause of hospitalization for infants in the United States; 50,000 to 80,000 hospitalizations annually are attributed to the virus, with the highest rates of hospitalization occurring during the first months of life. The Centers for Disease Control and Prevention has taken a two-pronged approach to combatting the problem. In August 2023, the Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, to protect infants younger than age 8 months against lower respiratory infection during their first RSV season and to protect children ages 8 to 19 months at increased risk for severe RSV disease who are entering their second RSV season. In September 2023, the FDA made available a maternal RSV vaccine to provide protection to the youngest infants.

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Omalizumab Reduced Allergic Reactions Across Multiple Food Allergies

It's estimated that food-related anaphylactic reactions result in 30,000 emergency department visits in the United States annually; more than 40% of children and more than 50% of adults with food allergies will experience at least one severe reaction yearly. The prevalence of IgE-mediated food allergies has been on the rise; it now affects approximately 3.4 million children and 13.6 million adults in the United States.

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Drug News Abstracts Archive

Drug News Abstracts - July 2023
Fruquintinib Prolongs Survival in Metastatic Colorectal CancerNealy 50% of patients with colorectal cancer will develop distant metastases, and the overall survival rate for these patients is about 15%. An international, randomized, double-blind, placebo-controlled, phase 3 study published in The Lancet demonstrated that fruquintinib, a selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 is effective as a treatment for such metastatic colorectal cancer.READ MORE...FRESCO-2 was conducted at 124 hospitals and cancer centers across 14 countries. It enrolled 691 patients with documented metastatic colorectal adenocarcinoma who had progressed on or been intolerant to cytotoxic and targeted therapies. They were randomly assigned to fruquintinib 50 mg (n = 461) or placebo (n = 230) once daily on days 1 to 21 in 28-day cycles. The patients had received a median of four lines of previous systemic therapy for the disease; 73% of patients had received more than three lines of therapy.The use of fruquintinib resulted in meaningful improvements in overall and progression-free survival among patients who had progressed or been intolerant to multiple previous therapies. At 6 months, 24% of the patients in the treatment group demonstrated progression-free survival, compared to 1% in the placebo group. The treatment group also had longer overall survival than the placebo group, with a 34% reduced risk of death. The median survival of patients in the fruquintinib group was 7.4 months, compared with 4.8 months in the placebo group (hazard ratio, 0.66).Adverse events were generally manageable, with minimal discontinuation due to treatment-related toxicity. Grade 3 or worse adverse events occurred in 286 (63%) who received fruquintinib and 116 (50%) who received placebo. The most common of these were hypertension (n = 62 [14%]), asthenia (n = 35 [8%]), and hand-foot syndrome (n = 29 [6%]). One treatment-related death occurred in each group.These data support the use of fruquintinib as a treatment option for patients with refractory metastatic colorectal cancer. Future research is needed, both to assess patient quality of life after fruquintinib therapy and the safety of the drug, and to determine the optimal sequencing strategy for patients with metastatic colorectal cancer who have failed at least two lines of therapy. (Dasari, A., et al. (2023). Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): An international, multicentre, randomised, double-blind, phase 3 study. The Lancet, 402(10395): 41–53. Retrieved June 2023 from – https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00772-9/fulltext#%20; Norris, J. (2023). New therapy may be on the horizon for metastatic colorectal cancer. Medical News Today. Retrieved June 2023 from https://www.medicalnewstoday.com/articles/new-therapy-may-be-on-the-horizon-for-metastatic-colorectal-cancerReleased: July 2023Nursing Drug Handbook© 2023 Wolters KluwerExamining Possible Association between Menopausal Hormone Therapy and DementiaIn a Danish nationwide, nested case-control study, exposure to menopausal hormonal therapy with estrogen and progestin was positively associated with development of all-cause dementia and Alzheimer disease, even with short-term usage around the age of menopause onset. The study identified 5,589 incident cases of dementia and 55,890 age-matched controls in Danish women ages 50 to 60 with no history of dementia or contraindications for menopausal hormone therapy. For all included participants, researchers assessed the history of menopausal hormone therapy in each patient starting from ages 45 to 55 up to 2 years before study initiation or dementia diagnosis. Using the program Medicin Macro, they were able to calculate probable daily dose and duration of medication use.READ MORE...The study examined the cohort for development of dementia, defined by first-time diagnosis or first-time use of dementia-specific medications. Compared with people who had never used estrogen-progestin therapy, those who did had an increased rate of all-cause dementia (hazard ratio [HR], 1.24). Increasing duration of use produced higher HRs, ranging from 1.21 for 1 year or less of use to 1.74 for more than 12 years of hormonal therapy. Both continuous (HR, 1.31) and cyclical (HR, 1.24) treatment regimens were associated with the development of dementia. This association persisted in women who received estrogen-progestin therapy at age 55 or younger (HR, 1.24); for those who initiated therapy at ages 45 to 50, HR was 1.26 and for those who initiated therapy at ages 51 to 60 years, HR was 1.21. It also held for either late-onset (HR, 1.21) or Alzheimer disease (HR, 1.22).Before the index date, 1,782 (31.9%) of patients with dementia and 16,154 (28.9%) of those in the control group had received menopausal treatment with estrogen-progestin. Among all users of estrogen-progestin, 66.2% had their last treatment day more than 8 years before the index date; 8.7% were still users at diagnosis or matching. Median age at initiation of estrogen-progestin was 53 years for both case and control groups; the median duration of use was 3.8 years for cases and 3.6 years for controls. Among those in the case group, 25.7% received continuous progestin, 38.9% received cyclical progestin, and 30.4% received both continuous and cyclical treatment before the index date. In the control group, among those who received hormonal therapy, 24.3% received continuous progestin, 38.9% received cyclical progestin, and 31.5% received both continuous and cyclical progestin.Further studies are necessary to determine whether these findings represent an actual effect of menopausal hormone therapy on dementia risk or whether they reflect an underlying predisposition in women in need of these therapies. In addition, the effect of short-term use of hormone therapy around the age of menopause remains to be fully explained. (Kantarci, K., & Manson, J. E. (2023). Menopausal hormone therapy and dementia. BMJ, 381, 1404. Retrieved June 2023 from https://www.bmj.com/content/381/bmj.p1404; Pourhadi, N., et al. (2023). Menopausal hormone therapy and dementia: Nationwide, nested case-control study. BMJ, 381, Article e072770. Retrieved June 2023 from https://www.bmj.com/content/bmj/381/bmj-2022-072770.full.pdf)Released: July 2023Nursing Drug Handbook© 2023 Wolters KluwerTezepelumab Effective in a Range of Severe Asthma TypesPost hoc pooled analysis of two studies of patients with severe asthma suggest that treatment with tezepelumab resulted in clinically meaningful reductions in asthma exacerbations, including those associated with hospitalization or an emergency department (ED) visit, across patient subgroups. Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin, which is released by airway epithelial cells in response to allergens or other triggers and drives airway inflammation. The two studies analyzed were PATHWAY, a phase 2 dose-finding study of tezepelumab in adults with inadequately controlled severe asthma, and NAVIGATOR, a phase 3 study of subcutaneous tezepelumab in adults and adolescents with severe asthma.READ MORE...The pooled analysis included patients ages 18 to 75 years in PATHWAY and ages 12 to 80 years in NAVIGATOR who had received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Overall, 1,334 patients were included (665 tezepelumab, 669 placebo). All patients had experienced at least two exacerbations of their asthma in the year before enrollment. The annualized asthma exacerbation rate (AAER) over 52 weeks was calculated both in the overall population and in subgroups defined by inflammatory biomarkers or clinical characteristics. To examine the reduction of AAER in patients across the spectrum of T2 inflammation, AAER reduction was assessed in patients grouped by combinations of baseline blood eosinophil counts (BEC), functional exhaled nitric oxide (FENO) levels, and perennial allergy status. Patients were grouped by combinations of low and high BEC (less than 150 cells/microliter, or greater than or equal to 150 cells/microliter) and low and high FENO levels (less than 25 ppb, or greater than or equal to 26 ppb).In both studies, treatment with tezepelumab reduced the AAER; in the pooled population, tezepelumab reduced AAER by 60% compared with placebo; clinically meaningful reductions in exacerbations were observed in patients with type 2-low disease, defined by low (less than 300 cells/microliter) or very low (less than 150 cells/microliter) baseline BEC, low FENO levels (less than 25 ppb), and negative perennial allergy status in the absence of maintenance corticosteroid use at baseline. Reductions in exacerbations ranged from 37% in type 2-low disease (BEC less than 300 cells/microliter, FENO levels less than 25 ppb) to 77% in type 2-high disease (BEC greater than or equal to 300 cells/microliter, FENO levels greater than or equal to 25 ppb). In the triple T2-low subgroup (BEC less than 150 cells/microliter, FENO levels less than 25 ppb, no perennial allergies), the AAER over 52 weeks was 34% lower with tezepelumab compared with placebo. Use of tezelepumab reduced rate of exacerbations requiring hospitalization or ED visit by 79% in the total population and by 60% in type 2-low disease and by 91% in type 2-high disease subgroups. The AAER among these patients remained consistent across baseline BECs but increased as baseline FENO levels increased. Exacerbations associated with hospitalizations or ED visit was decreased by 80% in patients with perennial allergies and by 74% in those without.Tezepelumab also improved lung function, asthma control, and asthma-related quality of life. In the overall population, the incidence of adverse events was similar between the two groups: in 75% of patients receiving tezepelumab and in 77% of patients receiving placebo. Serious adverse events were seen in 9% of patients receiving tezepelumab and in 13% of patients receiving placebo.Capturing a clear picture of the efficacy of tezepelumab in different subgroups is important as it represents the first in a new class of asthma medications. Real-world studies are warranted to further illuminate the drug's safety and its optimal use. (Brusselle, G., & Riemann, S. (2023). Is efficacy of Tezepelumab independent of severe asthma phenotype. Am J Respir Crit Care Med, 208(1), 1–3. Retrieved June 2023 from https://www.atsjournals.org/doi/epdf/10.1164/rccm.202304-0700ED?role=tab; Corren, J., et al. (2023). Efficacy of tezepelumab in severe, uncontrolled asthma: Pooled analysis of the PATHWAY and NAVIGATOR clinical trials. Am J Respir Crit Care Med, 208(1): 13–24. Retrieved June 2023 from https://www.atsjournals.org/doi/full/10.1164/rccm.202210-2005OC)Released: July 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - June 2023
Baclofen and Risk of EncephalopathyThe 30-day risk of encephalopathy was at least two times as high in patients treated with the muscle relaxant baclofen when compared with other muscle relaxants, tizanidine or cyclobenzaprine. This was demonstrated in an active comparator study conducted using new user data from the Geisinger Health System, a large tertiary health care system in Pennsylvania.READ MORE...Baclofen is a GABA agonist, and case reports and recent population-based studies have linked its use to encephalopathy in patients with kidney disease. It's thought that this encephalopathy is related to baclofen's effect on GABAB receptors, that excessive activation can reduce the release of neurotransmitters, resulting in disorientation and other cognitive impairments, and can also decrease cerebral blood flow and metabolic activity, leading to more severe symptoms.The study examined results in patients age 18 and older who were studied in two separate paired cohorts; cohort 1 compared baclofen and tizanidine, and cohort 2 compared baclofen and cyclobenzaprine. It balanced the cohorts on 45 patient characteristics and conducted subgroup analyses based on age, estimated GFR, sex, and concomitant opioid use.In cohort 1, the 30-day risk of encephalopathy was 64.7 per 1,000 person-years with baclofen compared to 28.3 per 1,000 person-years with tizanidine. The 30-day risk in cohort 2 was 52.6 per 1,000 person-years with baclofen compared to 22.3 per 1,000 person-years with cyclobenzaprine. The elevated risk, apparent as early as 30 days, persisted through the first year of treatment. In cohort 1, the subdistribution hazard ratio (SHR) of elevated encephalopathy risk at 30 days was 2.29; at 1 year, SHR with baclofen was 1.32. In cohort 2, the SHR at 30 days was 2.35; at 1 year, SHR with baclofen was 1.94. This increased risk remained consistent in all subgroup analyses.These findings may inform shared treatment decisions between patients and prescribers. Doctors and other prescribers could consider the use of alternative muscle relaxants or initiate baclofen at a lower dose, especially in patients with kidney disease. Patients should be educated to watch for the signs of the toxic effects, and health care providers should monitor for them. Finally, it might be appropriate for regulatory agencies to consider issuing warning labels about the potential risk, particularly in patients with chronic kidney disease. (Hwang, Y. J., et al. (2023). Baclofen and the risk of encephalopathy: A real-world, active-comparator cohort study. Mayo Clin Proceed, 98(5), 676&en688. Retrieved June 2023 from https://www.mayoclinicproceedings.org/article/S0025-6196(22)00649-8/fulltext; Muanda, F. T., et al. (2023). Reviewing the evidence of the association between baclofen and encephalopathy. Mayo Clin Proceed, 98(5), 647–649. Retrieved June 2023 from https://www.mayoclinicproceedings.org/article/S0025-6196(23)00134-9/fulltext)Released: June 2023Nursing Drug Handbook© 2023 Wolters Kluwer   Dupilumab Appears to be Superior Biologic for AsthmaA study using data from a single integrated health system suggests that dupilumab has the lowest overall risk of asthma-related exacerbations when compared with omalizumab and mepolizumab. Multiple biologics have been approved for treatment of asthma, but head-to-head comparisons of these biologics are lacking. Researchers conducted a retrospective cohort study that emulated a hypothetical randomized trial, a target trial to compare the effectiveness of these biologics in reducing asthma exacerbations and improving lung function.READ MORE...The agents in the analysis were omalizumab, an anti-IgE biologic approved for allergic asthma with sensitivity to perennial allergens and IgE levels between 30 and 700 kU/L; mepolizumab, an anti-IL-5 biologic effective in eosinophilic asthma with blood eosinophil counts of at least 150 cells/microliter; and dupilumab, an anti-IL-4 receptor biologic effective in both allergic and eosinophilic asthma. Using the integrated health records from the Massachusetts General Bingham Research Patient Data Registry, the study examined results for adults with moderate to severe asthma and no other chronic lung diseases; participants included 68 patients receiving dupilumab, 68 omalizumab, and 65 mepolizumab. Researchers examined for incidence of asthma-related exacerbations and change in baseline FEV1 value over 12 months of follow-up. Clinically significant exacerbations were defined as emergency department visits or hospitalizations with a primary diagnostic code for asthma or an outpatient prescription for corticosteroids in patients with asthma. Over 12 months of follow-up, asthma-related exacerbations occurred in 17 patients in the dupilumab group (25.0%), 28 patients in the mepolizumab group (43.1%), and 27 patients in the omalizumab group (39.7%). The number of exacerbations recorded and their incidence were as follows:dupilumab: 31 exacerbations (0.46 per person-year)omalizumab: 63 exacerbations (0.93 per person-year)mepolizumab: 86 exacerbations (1.32 per person-year)The adjusted incidence rate ratios (IRR) were 0.28 for dupilumab versus mepolizumab, 0.36 for dupilumab versus omalizumab, and 0.78 for omalizumab versus mepolizumab. Results were similar for adjusted IRR in patients with eosinophil counts of at least 300 cells/microliter: 0.26 for dupilumab versus mepolizumab and 0.33 for dupilumab versus omalizumab.At 12 months' follow-up, change from baseline in prebronchodilator FEV1 values was greater in patients receiving dupilumab than in those receiving mepolizumab (mean difference, 0.11 L) or in those receiving omalizumab (mean difference, 0.082 L), but were not statistically significant. (Akenroye, A. T., et al. (2023). Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation. J Allergy Clin Immunol, 151(5), 1269–1276. Retrieved June 2023 from https://www.jacionline.org/article/S0091-6749(23)00144-6/fulltext)Released: June 2023Nursing Drug Handbook© 2023 Wolters KluwerProphylactic Antiemetics before Apomorphine to Treat Parkinson Disease May Be UnnecessaryPost hoc analysis of data from the dose optimization phase of an open-label, long-term safety and efficacy study of sublingual apomorphine (SL-APO) in patients with Parkinson disease demonstrated rates of nausea and vomiting similar to those seen with other dopaminergic medications and with other apomorphine preparations. Nausea is common in patients with Parkinson disease, and many Parkinson disease medications in particular, levodopa and dopamine agonists can exacerbate nausea and vomiting. Because prophylactic antiemetics were used in clinical trials of apomorphine but not in trials of other dopamine agonists, the FDA recommends their use. This study evaluated the need for such antiemetics. U.S. prescribing information recommends prophylactic use of trimethobenzamide, but it has been in short supply and the alternative, domperidone, is not approved for use in the United States.READ MORE...Eligible patients had idiopathic Parkinson disease, were responsive to and were receiving stable doses of carbidopa-levodopa (with or without adjunctive medications), and had experienced at least one OFF episode per day with at least 2 hours of daily OFF time. During sequential office visits, patients underwent dose optimization (10 to 35 mg at 5-mg increments) when in an OFF state to determine the individualized dose that resulted in a tolerable FULL ON within 45 minutes. FULL ON was considered to be achieved when SL-APO treatment produced benefits in mobility, stiffness, and slowness; achieved adequate motor function to perform normal activities of daily living; and resulted in a response comparable or better than the patient's former responses to Parkinson disease medications. Once such a tolerable FULL ON dose was identified for the individual patient, the patient progressed into an open-label maintenance phase.The dose optimization population in the study included 449 patients; most were male (66.4%), white (96.0%), and had a mean age of 64.3 years. Of these 449 patients, 82.2% were new patients with no prior exposure to SL-APO, and all patients were also receiving carbidopa-levodopa. In the dose optimization phase of the trial, 88.4% (n = 397) successfully achieved an effective and tolerable dose; of these patients, 12.3% (n = 49) and 1.3% (n = 5) experienced vomiting during the optimization phase. Among those who had nausea and vomiting during dose optimization and continued into the long-term maintenance phase of the study, nausea occurred in 44.9% (22/49) and vomiting in 40.0% (2/5) during maintenance. Among those who had not experienced nausea and vomiting during dose optimization, 19.1% went on to report nausea and vomiting during maintenance.Of the patients in the dose optimization phase, 43.7% (n = 196) didn't use an antiemetic during that phase of the study; most of these patients (169/196) achieved an effective and tolerable SL-APO dose. Nausea and vomiting were uncommon in these patients: 12.2% (n = 24) had nausea, and 0.5% (n = 1) experienced vomiting. Nausea and vomiting were also seen among the 56.3% (n = 253) of patients who had used an antiemetic at any time during that phase of the study: 17.0% (n = 43) had nausea, and 2.4% (n = 6) experienced vomiting. Of the 67 patients who did experience nausea and the 7 who experienced vomiting, all events were mild to moderate, except for 1 severe occurrence of each.Importantly, less than half of all patients in this analysis who experienced nausea and vomiting went on to experience these events again during maintenance treatment, suggesting that patients can develop tolerance to those side effects over time. The choice of using prophylactic antiemetics should be made based on the individual's risks and benefits, as there may be patients who find it lessens their symptoms, but this research demonstrates that it's not necessary for most patients initiating SL-APO for treatment of OFF episodes in Parkinson disease. (Hauser, R. A., et al. (2023). Dose optimization of apomorphine sublingual film for OFF episodes in Parkinson's Disease: Is the prophylactic use of an antiemetic necessary? J Parkinson Dis, 13(3), 403–414. Retrieved June 2023 from https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd223537)Released: June 2023Nursing Drug Handbook© 2023 Wolters KluwerSpironolactone for Acne VulgarisThe Spironolactone for Adult Female Acne (SAFA) trial evaluated the effectiveness of the potassium-sparing diuretic against persistent facial acne in adult women in the UK when given in addition to standard topical treatments. Treatment guidance for acne recommends fixed-combination topical preparations containing retinoids, benzoyl peroxide, and antibiotics as first-line treatments. One-third of people under care for acne in the UK receive secondary treatment with long courses of oral antibiotics; given the increasing prevalence of antibiotic resistance, looking for an alternative is important. Spironolactone, which has been used off-label to treat acne, has been suggested as that alternative.READ MORE...In the pragmatic, multicenter, phase 3, double-blind, randomized controlled trial, study participants were older than age 18 with facial acne for at least 6 months, with acne of sufficient severity to warrant treatment by oral antibiotics, as judged by a clinician, and with an IGA of at least 2; 342 participants were included in the primary analysis. They were randomly assigned to either 50 mg/day spironolactone (n = 176) or matched placebo (n = 166) for 6 weeks, increasing to 100 mg/day up to week 24. At 24 weeks, the study was unblinded, and patients could choose to continue or start spironolactone. The mean age at baseline was 29.2 years; 46% had mild acne, 40% had moderate acne, and 13% had severe acne. Each participant underwent baseline assessments, including pregnancy tests, blood tests to exclude abnormal kidney function or hyperkalemia, a baseline photo, and contraceptive counseling. They were followed up at 6 weeks and 12 weeks, with a primary outcome assessment at 12 weeks, and longer-term follow-up by questionnaires from 24 weeks up to 52 weeks.Researchers measured effectiveness through the Acne-Specific Quality of Life questionnaire (Acne-QOL), which contains 19 questions organized into four domains (self-perception, social role, emotional role, and acne symptoms); each subscale has a range of 0 to 30, in which higher scores reflect improved QOL. Mean Acne-QOL acne symptoms subscale score was 13.2 for spironolactone at baseline and 12.9 for placebo. At week 12, scores had improved to 19.2 in the spironolactone group and 17.8 in the placebo group. The difference, 1.27, was small, but was statistically significant. At 24 weeks, the difference was greater: 3.45 (acne symptom subscale score 2.12 with spironolactone and 17.4 with placebo). More participants in the spironolactone group self-reported acne improvement than in the placebo group. No significant differences were noted at week 12 (72% of participants versus 68%), but the difference at week 24 (82% versus 63%) was significant (odds ratio, 1.16). The IGA of treatment success was demonstrated in 31/168 (19%) of those given spironolactone and in 9/160 (6%) of those given placebo. Most adverse reactions were mild; they were slightly more common in the spironolactone group, with more headaches reported than with placebo (20% versus 12%).Spironolactone improved acne on all outcomes tested, with significant differences at 24 weeks. It offers a useful alternative to oral antibiotics for women with persistent acne when first-line topical treatments have not worked. (Santer, M., et al. (2023). Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: Pragmatic, multicentre, phase 3, double blind, randomised controlled trial. BMJ; 381, e074349. Retrieved June 2023 from https://www.bmj.com/content/381/bmj-2022-074349; Santer, M., & Layton, A. (2023). What do we know about prescribing spironolactone for acne? BMJ, 381, 1114. Retrieved June 2023 from https://www.bmj.com/content/381/bmj.p1114)Released: June 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - May 2023
Evaluating Effectiveness of Text Reminders for Parents in Improving Influenza Vaccination RatesProviding an additional SMS text reminder to parents of children and adolescents with special risk medical conditions (SRMCs) in the context of tertiary care improves the receipt of influenza vaccine in those children. Children with SRMCs (for example, severe asthma, lung or heart disease, immunocompromise, or diabetes) are at increased risk for influenza-associated hospitalizations, intensive care unit admissions, mechanical ventilation, and death, so ensuring their vaccination is a priority in influenza immunization campaigns.READ MORE...The parallel-group randomized controlled trial was conducted in a single Australian public pediatric/obstetric hospital. The study enrolled 600 children and adolescents ages 6 months to 18 years with SRMCs who had an outpatient appointment scheduled during the 2021 Australian seasonal influenza season (from April to August). The patients were randomly assigned to a control group (n = 302; mean age, 11.4 years; 51.3% female) or to the SMS reminder text group (n = 298; mean age, 11.5 years; 54.4% female). The study examined Flutext-40, a nudge intervention, which included a parent-level nudge, in which an SMS text reminder was sent to the patient's primary caregiver. Clinician-level nudges were incorporated into standard practice at the facility and included prompt/reminder stickers and bookmarks placed in the medical record at relevant sites to facilitate vaccine recommendations. These, together with influenza vaccine signage placed around the facility and ensuring ease of access to the vaccine, made up the control intervention. In the SMS reminder arm, those randomized received all the control nudges and in addition had the parent-level nudge added. SMS text reminders were sent using a nondirective educational approach, advising that the child was eligible for a funded vaccine and could receive it at the hospital clinic or in the child's doctor's office. The reminder texts were timed to be sent before and after the child's scheduled specialist appointments during the study period, up to a maximum of three reminders. The SMS reminder intervention ceased if the parent replied that the child had been immunized. At trial conclusion, all participants received a text message with a link to a survey.The influenza vaccination rates increased from 26.2% (n = 79) in the control group to 38.6% (n = 113) with the addition of the SMS reminder (adjusted odds ratio, 1.79). The time to receipt of immunization was significantly shorter among the SMS reminder group (adjusted hazard ratio, 1.67). In the subgroup enrolled before June 15, a significantly greater proportion of patients in the SMS reminder group were vaccinated during the optimal delivery period for influenza vaccine (April to June 30); 40% of patients in this subgroup who received the SMS reminder (n = 50/197) were vaccinated at that time, compared to 25.4% of those in the control group (n = 50/197); adjusted odds ratio, 1.97. This is an important finding given the critical importance of timely immunization for this group. The parent acceptability survey offered at trial completion was completed by 40.3% of participants (n = 242/600); children of those who responded to the survey were more likely to have received the vaccine compared to overall trial participants (43.8%; n = 106/242 vs. 32.7%; n = 192/595).Studies have shown that children are more likely to receive the vaccine if parents remember receiving a recommendation from their child's specialist, but less than 58% of parents recall receiving such a recommendation. This intervention can alleviate that barrier. (Tuckerman, J., et al. (2023). Short message service reminder nudge for parents and influenza vaccination uptake in children and adolescents with special risk medical conditions: The Flutext-4U randomized clinical trial. JAMA Pediat, 177(4), 337-344. Retrieved May 2023 from https://jamanetwork.com/journals/jamapediatrics/fullarticle/2801662)Released: May 2023Nursing Drug Handbook© 2023 Wolters KluwerEarly Initiation of Growth Hormone Treatment Can Improve Outcomes in Children Born SGAEarly initiation of growth hormone (GH) therapy in children of short stature born small for gestational age (SGA) leads to favorable long-term growth outcomes in this cohort. Most children born SGA spontaneously catch up on their growth, but in approximately 10% of patients, short stature persists. GH therapy is prescribed for children who have not shown such spontaneous growth. Although it's recommended that such treatment begin before age 4, real-world data indicate that initiation is often delayed: mean age at initiation of GH treatment is 8.5 years in France, 7.7 years in Germany, and 7.1 years in the UK.READ MORE...Analysis of two multicenter observational studies assessing the long-term safety and effectiveness of GH therapy: the ANSWER Program (American Norditropin Studies: Web-Enrolled Research), conducted in 202 U.S. sites from 2002 to 2016, and NordiNet International Outcome Study, conducted in 469 European sites from 2006 to 2016, pooled data from children born SGA. The analysis assessed the impact of patient age at GH initiation on long-term growth outcomes in children SGA, through measures of height standard deviation score (HSDS), target height-adjusted HSDS, and ratio of bone age to chronological age (BA/CA ratio). Patients were categorized in three groups based on age at initiation of GH therapy (age 2 to less than 4 years, age 4 to less than 6 years, and age 6 and older). The effectiveness analysis included 3,318 patients who were treatment-naïve and were prepubertal at GH therapy initiation; 356 (10.7%) were age 2 to less than 4 years at initiation, 1,048 (31.6%) were age 4 to less than 6 years at initiation, and 1,914 (57.7%) were at least 6 years old at initiation.At GH therapy initiation, the mean HSDS was ~3.3 in the youngest group, ~3.1 in the middle group, and ~2.8 in the oldest group. After 4 years of GH therapy, mean HSDS were ~1.6 in the youngest, ~1.5 in the middle, and ~1.6 in the oldest group; after 8 years, mean HSDS were ~0.9 in the youngest, ~1.1 in the middle, and ~1.4 in the oldest group. The mean improvement in HSDS was significantly greater in the youngest group versus the oldest group both after 4 years of therapy (+1.73 versus +1.3) and after 8 years (+2.5 versus +1.7) and was significantly greater in the youngest group versus the middle group after 8 years (+2.5 versus +2.2). The mean improvement in the HSDS was also significantly greater in the middle group versus the oldest group both after 4 years (+1.6 versus +1.3) and after 8 years (+2.2 versus +1.7). No significant differences were seen in the BA/CA ratio between groups at 4 years (0.93 in youngest, 0.94 in middle, and 0.95 in oldest) and at 8 years (1.02 in youngest, 1.01 in middle, and 0.98 in oldest).Results demonstrate that younger age at start of treatment is associated with greater improvements in growth over the 8 years compared with other patients. It's also possible that the full benefits of early treatment initiation are still to be seen as the children in that youngest age group have the potential to continue growing. A longer follow-up period might demonstrate continued optimization of adult height. (Juul, A., et al. (2023). Early growth hormone initiation leads to favorable long-term growth outcomes in children born small for gestational age.J Clin Endocrinol Metab 108 (5),1043-1052. Retrieved May 2023 from https://academic.oup.com/jcem/article/108/5/1043/6873901)Released: May 2023Nursing Drug Handbook© 2023 Wolters KluwerComparing the Impact of Sacubitril-Valsartan on Heart Failure in Patients With Diabetes and Without DiabetesSacubitril-valsartan, a combination product consisting of sacubitril, a neprilysin inhibitor, and valsartan, an angiotensin-1 receptor antagonist, is a significant tool in the treatment of heart failure with reduced ejection fraction (HFrEF). A significant number of patients suffering from heart failure have concomitant type 2 diabetes, and the presence of these two conditions together increases the risk of mortality as the interaction may worsen both conditions.READ MORE...A single-center study compared the impact of sacubitril-valsartan use on echocardiographic parameters, arrhythmias, atrial fibrillation, and congestion rate in patients with HFrEF over 24-month follow-up and analyzed those findings according to whether the patients had diabetes. The study enrolled 240 consecutive patients with HFrEF who were treated with sacubitril-valsartan from 2016 to 2020; 87 patients had concomitant diabetes (median age, 68 years) and 153 didn't have diabetes (median age, 66 years). At baseline, patients with diabetes were more likely to also have arterial hypertension (87% versus 64%) and coronary artery disease (74% versus 60%).Over 24-month follow-up, improvement was seen on several parameters; in general, there were significant differences between patients with HFrEF and diabetes and those without concomitant diabetes. Median left ventricular ejection fraction (LVEF) increased significantly in patients without diabetes (from 27% interquartile range [IQR] to 35% IQR), but not in patients with diabetes (from 29% to 30% IQR). Systolic pulmonary artery pressure decreased in both groups, from 30 mm Hg to 25 mm Hg in patients without diabetes and from 34 mm Hg to 25 mm Hg in patients with diabetes, but there was no significant difference between the two groups.Median NT-brain natriuretic peptide (NT-proBNP) levels decreased significantly in patients without diabetes (from 1,445 pg/mL IQR to 491 pg/mL IQR) but not in patients with diabetes (from 1,395 pg/mL IQR to 885 pg/mL IQR). Median troponin-1 levels decreased significantly in patients without diabetes (from 0.099 ng/mL IQR to 0.023 ng/mL IQR) but not in patients with diabetes (from 0.05 ng/mL IQR to 0.02 ng/mL IQR). No significant differences were seen in other laboratory parameters, such as GFR, creatinine levels, and potassium levels.Measures on echocardiography didn't differ much except for the tricuspid annular plane systolic excursion, which was significantly increased in patients without diabetes (from 17 mm IQR to 18 mm IQR) and not in patients with diabetes (from 17.5 mm IQR to 18 mm IQR). Similar rates of ventricular tachyarrhythmias were observed in both groups, but the congestion rate decreased significantly in both groups, decreasing from 44.4% before sacubitril-valsartan treatment to 13.5% after 24 months in patients with diabetes and from 28.4% before treatment to 8.4% after 24 months in patients without diabetes.The all-cause mortality rate was higher in patients with diabetes compared to those without concomitant diabetes (25% versus 8.1%). But even this mortality rate reflects an improvement over that found in published data in patients with HFrEF and diabetes not treated with sacubitril-valsartan. The study illustrates the more complicated course of HFrEF with concomitant diabetes but demonstrates that sacubitril-valsartan is still effective in these patients. (El-Battrawy, I., et al. (2023). The impact of sacubitril/valsartan on outcome in patients suffering from heart failure with a concomitant diabetes mellitus. ESC Heart Failure, 10, 943-954. Retrieved May 2023 from https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.14239)Released: May 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - April 2023
Dostarlimab Improves Survival in Endometrial CancerEndometrial cancer is the sixth most common cancer among women worldwide and the second most common type of gynecologic cancer. Standard treatment is chemotherapy with carboplatin plus paclitaxel; however, long-term outcomes remain poor, with median overall survival of less than 3 years. In a phase 3, double-blind, multicenter, randomized, controlled trial, adding the immune checkpoint inhibitor dostarlimab to this combination therapy significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in a subset of patients.READ MORE...The study randomly assigned 494 patients with primary advanced stage 3 or 4 or first recurrent endometrial cancer to 500 mg dostarlimab (n = 245) or placebo (n = 249) in addition to the usual chemotherapy—carboplatin (AUC, 5 mg/mL/min) and paclitaxel (175 mg/m2 BSA)—every 3 weeks for 6 cycles, followed by 1,000 mg dostarlimab or placebo every 6 weeks, continuing treatment for up to 3 years or until disease progression, discontinuation, or death. Of this total, 118 patients had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors. These dMMR–MSI-H tumors occur in 25% to 30% of endometrial cancers; they are marked by increased expression of programmed cell death (PD-1) receptors and its ligands (PD-L1 and PD-L2). Dostarlimab is an immune checkpoint inhibitor targeting the PD-1 receptor.As of data cutoff, 88 patients in the overall trial population were still receiving treatment in one of the two groups. The researchers examined progression-free survival, as assessed using Response Evaluation Criteria in Solid Tumors (RECIST), and for overall survival. Imaging to assess status of the cancer was performed every 6 weeks to week 25, then every 9 weeks until week 52, and then every 12 weeks until progressive disease was documented in accordance with RECIST. Results were stratified according to MMR-MSI status, whether patients had received previous external pelvic radiotherapy, and disease status.In the overall population with endometrial cancer, progression-free survival at 24 months was 36.1% with dostarlimab and 18.1% with placebo (hazard ratio [HR], 0.64). Overall survival in the total population at 24 months was 71.3% with dostarlimab and 56.0% with placebo (HR, 0.64). Of the 118 patients with dMMR–MSI-H tumors, progression-free survival at 24 months was 61.4% with dostarlimab and 15.7% with placebo (HR, 0.28). Overall survival in the dMMR–MSI-H population was 83.3% with dostarlimab and 58.7% with placebo (HR, 0.30).The progression-free survival benefit seen with dostarlimab does not appear to be consistent across all tumor subgroups except in the dMMR–MSI-H population, where the regimen provided a significant benefit, with a 64.1% probability of progression-free survival. Extended follow-up may be necessary to observe a treatment effect in other subgroups, especially in those with stage 3 disease. (Mirza, M. R., et al. (2023). Dostarlimab for primary advanced or recurrent endometrial cancer. New Engl J Med. Retrieved April 2023 from https://www.nejm.org/doi/full/10.1056/NEJMoa2216334?query=main_nav_lg)Released: April 2023Nursing Drug Handbook© 2023 Wolters KluwerIV Methylprednisolone to Treat Pediatric Complications of SARS-CoV2 InfectionBy April 2020, clusters of children who had been infected with SARS-CoV2 began presenting with a new inflammatory disease with similarities to Kawasaki disease. The emergence of this disorder, labeled PIMS-TS (pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV2 infection), led to widespread use of anti-inflammatory treatments. No clinical trials have been conducted to provide evidence to support such use; rather, choice of such treatments has been guided by expert opinion and consensus guidelines, which recommend use of IV glucocorticoids and immunoglobulins as initial treatment of PIMS-TS, with biological disease-modifying antirheumatic drugs being used in more severe cases.READ MORE...An open-label, multicenter, randomized controlled trial conducted at 10 Swiss hospitals is the first reported that compared the two most used anti-inflammatory treatments in these patients. The study, Swissped RECOVERY, was published in The Lancet Child and Adolescent Health, and enrolled 75 patients between May 2021 and April 2022. The patients, children hospitalized with PIMS-TS, were randomized to IV methylprednisolone (10 mg/kg/day for 3 days; n = 37) or IV immunoglobulins (2 g/kg as single dose; n = 38). Patients were eligible for study if the attending practitioner considered them candidates for IV anti-inflammatories; although patients could receive additional anti-inflammatory medications, they had to be observed for at least 24 hours after starting the randomized treatment before doing so. All other treatments given to the patients in the study were reviewed by a committee who were masked as to which treatment group the patient was assigned to.The study compared the two treatments on length of hospitalization to day 28, death, or discharge, and measured the proportion of patients requiring organ support and the duration of such support. They found few differences between the two treatments. The average length of hospital stay was 6.0 days in both groups. But fewer patients in the methylprednisolone group (10/37; 27%) required respiratory support at any time during treatment compared with patients in the immunoglobulin group (21/38; 55%). When comparing the need for respiratory support after randomization, this possible benefit for methylprednisolone still appeared to hold: 3/37 (8%), compared to 11/38 (29%) in the immunoglobulin group. Other outcomes—duration of respiratory support, need for inotropes, intensive care unit admission, cardiac effects after baseline, major bleeding, and thrombotic events—did not differ significantly between the two groups. No children died, and only one was still hospitalized after 28 days.These findings need confirmation because the sample size was so small; hopefully, long-term follow-ups of other cohorts in the RECOVERY trial can provide a clearer picture. But they do offer evidence that methylprednisolone could be acceptable as first-line treatment of PIMS-TS, given that it’s a more affordable and more widely available medication. (Welzel, T., et al. (2023). Methylprednisolone versus intravenous immunoglobulins in children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): An open-label, multicentre, randomised trial. Lancet Child Adolesc Health, 7(4), 238–248. Retrieved April 2023 from https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(23)00020-2/fulltext)Released: April 2023Nursing Drug Handbook© 2023 Wolters KluwerCDC Describes Monkeypox Vaccine Coverage in the United StatesFrom May 2022 through January 2023, 30,157 cases of monkeypox and 32 associated deaths were reported in the United States (with more than 85,000 cases worldwide). Despite a steady decline in cases from a 7-day daily average of more than 400 cases on August 1, 2022, to 5 cases on January 31, 2023, vaccination is still recommended for patients at risk.READ MORE...Injection of Jynneos (modified vaccinia Ankhara vaccine) has been shown to be effective in preventing monkeypox; the Centers for Disease Control and Prevention (CDC) has published data estimating how successful vaccination campaigns have been in providing coverage among populations at risk for monkeypox. Despite the administration of more than 1 million doses of Jynneos (734,510 first dose and 452,884 second dose), the CDC finds that these numbers equate to only 23% of those most at risk being fully vaccinated, with 37% having received just one dose. Those at increased risk include the following:persons with known or presumed exposure to monkeypoxmen who have sex with men (MSM) and gender-diverse persons (transgender, nonbinary, or other gender-diverse individuals) with multiple recent sexual partnersMSM and gender-diverse individuals with newly diagnosed sexually transmitted diseasepersons who have had sex at a commercial sex venue or other large social-cultural gathering during the previous 6 monthsthose with sexual partners with any of the aforementioned riskspersons with HIV or other immunosuppression who might be exposed due to any of these scenarios.The CDC calculated vaccination coverage for each state and U.S. territory, and further determined coverage for various jurisdictions, including major cities. The analysis was done using a numerator created from information on vaccinated individuals in each region and a denominator that represented persons in that region at risk for monkeypox virus exposure. This figure was determined as the number of MSM who met indications for preexposure prophylaxis plus the number of MSM with HIV in the region plus 25% to account for others at risk. Using this formula, only Washington DC is estimated to have achieved at least 50% full (two-dose) vaccine coverage. Those areas with more than 50% single-dose vaccine coverage included these regions:Washington, DC (94.8% coverage)New York City (88.8% coverage)California (61.4% coverage)Rhode Island (58.9% coverage)Massachusetts (53.9% coverage)New York State excluding New York City (50.1% coverage).Three of these six areas (New York City, California, New York State) were also areas with the highest monkeypox case counts. But in 22 of the regions studied by the CDC, vaccination coverage with one dose was less than 25%. Within this low uptake of the vaccine, a special area of concern is that outreach may be failing to reach those most affected; for example, although approximately 1 in 3 monkeypox cases in the United States occurred in Black persons, only 1 in 8 single-dose recipients were Black. The CDC notes that this less-than-optimal uptake has numerous causes:Lower vaccine availability and awarenessFewer vaccination providers in those regionsLower confidence in vaccines and therefore lower demandConcerns about stigma.The CDC has recently made the vaccine available in an intradermal form under an Emergency Use Authorization, noting that, because each intradermal dose is one-fifth the size of a subcutaneous dose, this strategy can increase availability of the vaccine. But clearly, it’s important to find and use strategies to advance health equity among those most affected by the epidemic. This remains true even as the incidence of infection from this outbreak declines. (Owens, L. E., et al. (2023). JYNNEOS vaccination coverage among persons at risk for Mpox – United States, May 22, 2022 – January 31, 2023. MMWR, 72(13), 342–347. Retrieved April 2023 from https://www.cdc.gov/mmwr/volumes/72/wr/mm7213a4.htm?s_cid=mm7213a4_w)Released: April 2023Nursing Drug Handbook© 2023 Wolters KluwerData on Long-Term Safety and Efficacy of Risdiplam in Spinal Muscular AtrophyNew 4-year data presented at the Muscular Dystrophy Association’s Clinical and Scientific Conference, held in March 2023, demonstrate that the findings of the SUNFISH study have persisted. Data from SUNFISH, which examined the safety and efficacy of risdiplam in people with type 2 and nonambulant type 3 spinal muscular atrophy (SMA), showed that increases in motor function that were seen in the first year of the study have been maintained through the fourth year.READ MORE...SMA is caused by a mutation in the SMA1 gene, which codes for survival motor neuron protein, which is critical to maintaining healthy motor neurons. Risdiplam, an orphan drug, is an SMN2 splicing modifier that treats SMA by increasing and sustaining production of SMN protein in the CNS and peripheral tissues.The SUNFISH trial was designed to evaluate risdiplam effects on motor function. It enrolled 180 patients with SMA, all of whom could sit independently but were not able to walk. It evaluated changes in motor function by measuring motor function on the Motor Function Measure-32 (MFM-32) and the Revised Upper Limb Module (RULM), as well as on the Hammersmith Functional Motor Scale Expanded (HMSE). The study showed a statistically significant change from baseline in MFM-32 score at 12 months in patients treated with risdiplam (n = 120) versus placebo (n = 60). Findings from RULM were also statistically significant in the primary trial, with HMSE hinting at benefits but not reaching significance. The greatest improvement in motor function, as assessed by MFM-32 score, was seen in the youngest age group (ages 2 to 5); 78.1% of those receiving risdiplam showed meaningful improvement compared to 52.9% of those on placebo. In older patients, stabilization is a more realistic goal; the oldest group (ages 18 to 25) showed stabilization in 57.1% of patients in the risdiplam group versus 37.5% of patients in the placebo group. Patients and caregivers also completed the SMA Independence Scale-Upper Limb Module, reporting improvements or stabilization in ability to carry out activities of daily living (ADLs).The poster presentation at the MDA meeting demonstrated that these findings have remained generally stable over 4 years, with patients maintaining the improvements or stabilization of motor function from the original trial, demonstrating long-term efficacy. The overall rate of adverse events continued to decrease over the 48 months. In addition, patients and caregivers continued to report better performance on the SMA Independence Scale, which measures the assistance required to complete ADLs, such as feeding, brushing teeth, getting dressed, or writing, than before beginning risdiplam treatment. Patients and caregivers reported continuous improvement or stabilization in the level of assistance needed to perform ADLs. (Genentech. Press release. 19 March 2023. New four-year data for Genentech’s Evrysdi reinforce long-term efficacy and safety profile in some of the most severely affected people with types 2 and 3 spinal muscular atrophy (SMA). Retrieved April 2023 from https://www.gene.com/media/press-releases/14985/2023-03-19/new-four-year-data-for-genentechs-evrysd; Genentech. MEDically. Conference report. 19 March 2023. SUNFISH parts 1 and 2: 4-year efficacy and safety of risdiplam in types 2 and 3 SMA. Retrieved April 2023 from https://medically.gene.com/global/en/unrestricted/neuroscience/MDA-2023/mda-2023-poster-day-sunfish-parts-1-and-2-4-year-effica.html; SMA Today. 22 March 2023. MDA 2023: Evrysdi’s motor benefits found to last for 4 years in trial. Retrieved April 2023 from https://smanewstoday.com/news/mda-2023-evrysdi-motor-benefits-last-4-years-sunfish-trial-data/)Released: April 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - March 2023
Decreasing Risk of Relapse after Anti-TNF Withdrawal in Inflammatory Bowel DiseaseDe-escalation of anti-tumor necrosis factor (TNF) treatment in patients with inflammatory bowel disease (IBD) in remission is a strategy to reduce the side effects of the treatment, including the risks of serious infections and malignancies, while decreasing health care expenditures and treatment burdens. But this strategy is associated with a high relapse rate. A prospective observational study from the Netherlands offers data that can guide clinicians and inform patient selection for such treatment de-escalation. The study concludes that strict patient selection based on endoscopic healing as well as the maintenance of mesalamine treatment in ulcerative colitis may lower the risk of relapse.READ MORE...The multicenter, prospective study in adult patients with Crohn disease (CD), ulcerative colitis, or IBD – unclassified (IBDU) enrolled 81 patients, 51% with CD, with a median follow-up of 2 years. Those included in the study had achieved at least 6 months of corticosteroid-free clinical remission and endoscopic healing and had elected to discontinue anti-TNF therapy between 2018 and 2020. Researchers evaluated the following as potential predictors of relapse:complete endoscopic healing: endoscopic Mayo score of 0 or Simple Endoscopic Score for CD (SES-CD) of 0 to 2partial endoscopic healing: endoscopic Mayo score of 1 or SES-CD of 3 to 4anti-TNF agent trough levelsuse of immunomodulators or mesalamine.The patients could continue or start mesalamine or immunomodulator (thiopurine or methotrexate) treatment at the discretion of the treating physician. Follow-up started at the time of the last dose of the anti-TNF agent, and patients were monitored by measuring C-reactive protein (CRP) and fecal calprotectin at 3, 6, 12, and 24 months and by endoscopy at 12 weeks. In addition, if relapse occurred, monitoring included CRP, fecal calprotectin, and anti-TNF trough levels at 3 months. In addition, the following questionnaires were sent to participants at 0, 3, 6, 12, and 24 months of follow-up, at time of relapse, and 3 months after relapse:Harvey-Bradshaw Index (HBI) for CD patientsSimple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis and IBDU patientsShort IBD Quality of Life Questionnaire (SIBDQ) for all patients.Clinical remission was defined as SCCAI/HBI scores <5; biochemical remission was defined as CRP <10 mg/L and fecal calprotectin <250 mcg/g; endoscopic healing was defined as Mayo score <2 or SES-CD <5 without large ulcers; and clinical relapse was defined as SCCAI/HBI score ≥5 with ≥3-point increase from baseline.All patients in the study met the criteria for endoscopic healing, and 71 had complete endoscopic healing. The risk of relapse after withdrawal of anti-TNF treatment among patients with any endoscopic healing remained high, but complete endoscopic healing was associated with a considerably lower risk of relapse. At 12 months, 7 patients (70%) with partial endoscopic healing had relapsed, compared with 25 patients (35%) with complete endoscopic healing. The large difference in this relapse risk underscores the clinical importance of this finding.The use of mesalamine was independently associated with a decreased risk of relapse in patients with ulcerative colitis/IBDU (adjusted hazard ratio, 0.08) but not CD. However, continuing treatment with immunomodulators does not offer such protection. It’s possible that selection bias may have played a part in this result, since the decision to continue or start these agents was up to the treating physician. No other potential predictors for relapse were identified on analysis. After relapse, 30 patients restarted anti-TNF therapy (26 with the same agent), and clinical remission was regained in 73% at 3 months and 90% at 12 months. The remission rate at 3 months did not differ between patients restarting single-agent anti-TNF therapy or those restarting with combination therapy (77% vs. 67%). Reported quality of life and general well-being improved to baseline once remission was restored.  This underscores the feasibility of a strategy of combining withdrawal with reintroduction upon relapse. (Mahmoud, R., et al. (2023). Complete endoscopic healing is associated with lower relapse risk after anti-TNF withdrawal in inflammatory bowel disease. Clin Gastroenterol Hepatol, 21(3), 750–760.E4. Retrieved March 2023 from https://www.cghjournal.org/article/S1542-3565(22)00820-5/fulltext)Released: March 2023Nursing Drug Handbook© 2023 Wolters Kluwer Azithromycin Given during Labor Reduces Risk of Maternal Postpartum SepsisA single dose of azithromycin given during labor reduces the risk of maternal sepsis and death after childbirth. The World Health Organization has prioritized reduction of maternal sepsis in its efforts to decrease maternal deaths worldwide. Sepsis is a life-threatening condition that occurs as the immune system overreacts to infection, leading to tissue and organ damage. It accounts for 10% of maternal deaths and is among the top three causes of maternal deaths worldwide.READ MORE...Azithromycin is effective against a wide range of bacteria and has been shown to reduce maternal infection when given IV during cesarean delivery, reducing risk by 50%. A large multinational trial that enrolled more than 29,000 women in 7 member countries of the Global Network for Women and Children’s Health Research, A-PLUS (Azithromycin Prevention in Labor Use Study) was conducted between September 2020 and August 2022. The trial enrolled women in labor at 28 weeks’ gestation or more; who had no known infections, cardiac issues, or known allergies to antibiotics; and who were not in an advanced stage of labor (that is, dilation >6 cm). Enrolled patients were randomized to receive a 2-g oral dose of azithromycin (N = 14,590 women, 14,687 neonates) or placebo (N = 14,688 women, 14,782 neonates). The outcomes were a composite of maternal sepsis or death and a composite stillbirth or neonatal death or sepsis. Patients were educated about what signs or symptoms of infection to watch for and when to report those or to return for further health care; the researchers implemented guidelines to monitor patient’s temperature.Only 1.6% (n = 277) of women who received azithromycin developed sepsis or died within 6 weeks after delivery, compared to 2.4% (n = 344) who received a placebo dose (relative risk, 0.67). The differences in the maternal primary outcome appear to mostly be due to the decreased incidence of sepsis (1.5% azithromycin [n = 219] vs. 2.3% placebo [n = 339]), with a relative risk of 0.65. Death from sepsis occurred in less than 0.1% of each group. Those who received the dose of azithromycin were also less likely to develop endometriosis and other infections and had fewer hospital readmissions and unscheduled health care visits compared with placebo. Endometriosis occurred in 1.3% of patients in the azithromycin group and in 2.0% of those in the placebo group (relative risk, 0.66). Wound infection, whether of cesarean incision or perineal injury, occurred in 1.6% of those in the azithromycin group and in 2.2% of those in the placebo group (relative risk, 0.71).The incidence of stillbirth or neonatal death or sepsis was similar in the two groups: 10.5% in the azithromycin arm (n = 1,540) vs. 10.3% in the placebo arm (n = 1,526); relative risk, 1.02. Neonatal sepsis occurred in 9.8% (n = 1,433) and 9.6% (n = 1,407) of infants in the azithromycin and placebo arms, respectively. Incidence of stillbirth (0.4%) and neonatal deaths (1.5%) did not differ in the two groups.These findings can lead to a simple intervention that will be lifesaving, especially in low- and middle-income countries. (Alpha Galileo. SciDev.Net. (2023). Preventative antibiotic during labour “saves lives.” Retrieved March 2023 from https://www.alphagalileo.org/en-gb/Item-Display/ItemId/230703?returnurl=https://www.alphagalileo.org/en-gb/Item-Display/ItemId/230703; Tita, A. T. N., et al. (2023). Azithromycin to prevent sepsis or death in women planning a vaginal birth. New Engl J Med, 388, 1161–1170. Retrieved March 2023 from https://www.nejm.org/doi/full/10.1056/NEJMoa2212111)Released: March 2023Nursing Drug Handbook© 2023 Wolters Kluwer Remdesivir for Severe COVID-19: Who Benefits?The broad-spectrum antiviral medication remdesivir was one of the first medications approved for treatment of COVID-19, as early as 2020. A new review of eight clinical trials, including meta-analysis of individual patient data, allows identification of the subgroup that can most benefit from remdesivir treatment. The meta-analysis showed reduced mortality in patients hospitalized with COVID-19 who required no respiratory support or only conventional low-flow oxygen.READ MORE...A research team from the University of Basel analyzed results from eight randomized, controlled trials (RCTs) that assessed the benefits and harms of remdesivir compared with placebo or usual care in these patients. The analysis included data from more than 10,000 unvaccinated patients from more than 40 countries who were treated for COVID-19 in hospital between February 2020 and April 2021, more than 99% of the patients involved in RCTs on this topic worldwide. Results of the meta-analysis were published in The Lancet Respiratory Medicine.Remdesivir lowered mortality over a 4-week observation period by roughly 2%, leading to 20 fewer deaths per 1,000 patients. Within 28 days of randomization, 662 (12.5%) of 5,317 patients assigned to remdesivir and 706 (14.1%) of 5,005 patients not assigned to remdesivir died (adjusted odds ratio [OR], 0.88). Meta-analysis showed that patients who didn’t receive oxygen treatment or only received conventional oxygen support experienced a significant survival benefit from remdesivir. Out of those who received no oxygen support or low-flow oxygen, 409 (9.1%) of 4,773 patients assigned to remdesivir compared with 465 (11.2%) of 4,159 patients not assigned to remdesivir died (adjusted OR, 0.8); however, no significant difference was seen for those who received more respiratory support: among those who received high-flow oxygen or ventilation, 253 (30%) of 844 patients assigned to remdesivir died compared to 241 (28.5%) of 846 patients not receiving remdesivir (adjusted OR, 1.01). No credible subgroup effect was found for other variables, such as time after symptom onset that remdesivir treatment began, patient age, presence of comorbidities, the enrollment period, or corticosteroid use.The number of patients either requiring new mechanical ventilation or dying up to day 28 was also lower in the remdesivir group: 988 of 5,346 patients (18.5%) vs. the non-remdesivir group: 1,123 of 5,034 patients (22.3%) (adjusted OR, 0.81). Remdesivir use was not associated with earlier discharge from the hospital; the absolute difference in median time to hospital discharge was 0.16 days.These results align with World Health Organization guidelines, which recommend remdesivir for patients with severe but noncritical COVID-19 infection. Further study is needed to determine the absolute risk reduction in a better-protected population. Further research can determine the effect size in patients who have received a complete series of COVID-19 vaccine or booster doses and in those with immunity from prior COVID-19 infection. (Alpha Galileo. University of Basel. (2023). When is remdesivir effective for COVID-19? Retrieved March 2023 from https://www.alphagalileo.org/en-gb/Item-Display/ItemId/230551?returnurl=https://www.alphagalileo.org/en-gb/Item-Display/ItemId/230551; Amstutz, A., et al. (2023). Effects of remdesivir in patients hospitalised with COVID-19: A systematic review and individual patient data meta-analysis of randomised controlled trials. Lancet Respir Med. Advance online publication. Retrieved March 2023 from https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(22)00528-8.pdf)Released: March 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - February 2023
Momelotinib a Good Choice for Myelofibrosis with Anemia Treatment with momelotinib resulted in clinically significant improvements in patients with myelofibrosis. Improvements were seen in myelofibrosis-associated symptoms, measures of anemia, and spleen response when compared to the Janus kinase (JAK) inhibitor danazol. Impaired JAK signaling in myelofibrosis drives overproduction of inflammatory cytokines, bone marrow fibrosis, and systemic symptoms, as well as splenomegaly. The resulting chronic inflammation drives hyperactivation of the protein activin A receptor, type 1 (ACVR1) and elevated hepcidin, dysregulated iron metabolism, and anemia. JAK inhibitors disrupt this pathway, reducing spleen size and the symptom burden of myelofibrosis. Momelotinib, a first-in-class inhibitor, not just of JAK1 and JAK2, but also of ACVR1, also disrupts the hepcidin pathway, improving anemia over time.READ MORE...MOMENTUM is an ongoing double-blind, randomized phase 3 study of momelotinib vs. danazol in symptomatic, anemic patients who had already received treatment with JAK inhibitors. The study enrolled 195 patients at 107 sites across 21 countries; patients were at least 18 years old, had confirmed diagnosis of primary myelofibrosis, post-polycythemia vera, or post-essential thrombocytopenia myelofibrosis. Patients were randomly assigned to receive 200 mg momelotinib PO once daily plus placebo or 300 mg danazol PO twice daily plus placebo; 130 patients were assigned to the momelotinib group and 65 patients to the danazol group. MOMENTUM was conducted from April 2020 to December 2021, with a 24-week treatment period. The study was blinded for those 24 weeks, and then patients could enter an open-label crossover phase, during which they received 200 mg/day momelotinib.The study examined the total symptom score (TSS) response rate on the Myelofibrosis Symptom Assessment Form at week 24. Response was defined as a 50% or greater reduction in mean TSS, compared with baseline. A significantly greater proportion of patients in the momelotinib group reported such response than in the danazol group: 25% (32/130) vs. 9% (6/65). The week 24 symptom response was sustained through week 48 in almost all patients, and new responders were observed at week 48 among those who were nonresponders at week 24: 12/61 in the momelotinib arm and 10/35 in the danazol arm.Approximately half of the patients were transfusion-dependent at baseline (that is, needing 4 units or more of red cell or whole blood transfused in the 8 weeks before study initiation), with an additional 35% requiring some transfusion support. Week 24 transfusion independence (TI) response was seen in 31% in the momelotinib group and in 20% in the danazol group. TI responses at week 24 were also sustained through week 48 in 90% of patients who had initiated treatment with momelotinib and in 77% of those who had initiated treatment with danazol before the crossover phase. (Verstovsek, S., et al. (2023). Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): Results from an international, double-blind, randomized, controlled, phase 3 study. Lancet, 401 (10373): 269–280. Retrieved February 2023 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02036-0/fulltext; Gerds, A. (2023 ). Updated results from the MOMENTUM phase 3 study of momelotinib (MMB) vs. danazol (DAN) in symptomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor . OncLive. [Video]. Retrieved February 2023 from https://www.onclive.com/view/updated-results-from-the-momentum-phase-3-study-of-momelotinib-mmb-versus-danazol-dan-in-symptomatic-and-anemic-myelofibrosis-mf-patients-previously-treated-with-a-jak-inhibitor)Released: February 2023Nursing Drug Handbook© 2023 Wolters Kluwer Novel Oral Poliovirus Vaccine Type 2 and Newborns A phase 2, randomized, double-blind, controlled trial published in  The Lancet  offers data that novel oral poliovirus vaccine type 2 (nOPV2), which has previously been studied in populations who have already been vaccinated against polio, was safe and immunogenic in newborns who had not received any other poliovirus vaccine.READ MORE...The leading cause of poliomyelitis currently is type 2 circulating vaccine-derived poliovirus (CVDPV2) from Sabin oral poliovirus vaccines (OPVs). Attenuated polioviruses can mutate, and the mutation can result in vaccine-associated polio in vaccine recipients and susceptible close contacts; in settings where immunization coverage is poor, this can lead to the emergence of CVDPVs. To mitigate these risks, the nOPV2 has been developed to be more genetically stable, reducing the risk of CVDPV2, to which unvaccinated newborns are especially vulnerable.The study randomized 330 infants from a single health research center in Bangladesh to receive either two doses of nOPV2 (n = 220) or placebo (n = 110), administered at age 0 to 3 days and at age 4 weeks. The two study groups were similar in sex as well as birth weight and birth length of the infants. Infants were excluded from the study for previous receipt of poliovirus or rotavirus vaccine, infection or illness at the time of enrollment, suspicion of immunodeficiency in the infant or a close family member, or contraindication to venipuncture.Poliovirus neutralizing antibody responses were measured in sera drawn at birth and at age 4 weeks and 8 weeks. At birth, nearly all infants (93%) had seroprotective maternal antibodies against type 2 polioviruses; by week 8, only 56% of the placebo group still retained these maternal antibodies. Of the 16 infants in the nOPV2 group who were initially unprotected at birth, with no detectable titers, 8 had seroprotective titers by week 4 and all had seroprotective antibodies by week 8.The vaccine was as well tolerated as placebo, causing only mild or moderate adverse events: 154 (70%) in the nOPV2 group and 78 (71%) in the placebo group. No immediate reactions were seen within 30 minutes of vaccination. The most frequent solicited events were instability, abnormal crying, and poor feeding. Severe unsolicited events were reported in 11 (5%) vaccine recipients and in 5 (5%) placebo recipients, most commonly pneumonia.More than 450 million doses of this vaccine have already been distributed to control CVDPV2 outbreaks, and it has been important to determine safety in young infants, as they are among those at highest risk in these outbreaks. The study found no detectable shedding of poliovirus in baseline stool samples; 2 weeks after the first vaccine dose, type 2 viral shedding was detectable in 52% of recipients; 2 weeks after the second vaccine, viral shedding had increased to 64%, before gradually decreasing to nearly 0 by week 12. These data are helpful for health care administrators and others responsible for implementing such vaccination campaigns. (Slomski, A. (2023). Novel oral polio vaccine safety induces antibodies among vaccine-naïve infants.  JAMA, 329 (4), 279. Retrieved February 2023 from https://jamanetwork.com/journals/jama/fullarticle/2800664; Zaman, K. (2023). Evaluation of the safety, immunogenicity, and faecal shedding of novel oral polio vaccine type 2 in healthy newborn infants in Bangladesh: A randomized, controlled, phase 2 clinical trial.  Lancet, 401 (10371), 131–139. Retrieved February 2023 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)02397-2/fulltext)Released: February 2023Nursing Drug Handbook© 2023 Wolters Kluwer Effectiveness of Outpatient SARS-CoV2 Treatments in Patients with Systemic Autoimmune Rheumatic Disease The risk of severe COVID-19 infection is cause for concern in patients with systemic autoimmune rheumatic disease and immunosuppression. Even in a cohort of these patients who were mostly vaccinated against SARS-CoV2, outpatient treatment substantially reduced odds of severe COVID-19 outcomes compared with no outpatient treatment. These are the findings of a retrospective cohort study conducted in an integrated health care system in Boston. This is one of the first studies to evaluate outpatient SARS-CoV2 treatments among patients with systemic autoimmune rheumatic disease that includes oral outpatient treatment options and quantifies the prevalence of COVID-19 rebound.READ MORE...Researchers identified 704 patients age 18 or older with preexisting systemic autoimmune rheumatic disease who had COVID-19 onset between January and May 2022. Using data from the electronic medical record, researchers identified SARS-CoV2 infection by record of positive PCR or antigen test results, rheumatic disease by diagnosis codes and immunomodulator prescriptions, and outpatient COVID-19 treatment by prescription. If the patient received more than one outpatient COVID treatment, it was classified as combination treatment. Mean age of patients selected was 58.4 years; 76% were female and 84% were white. Of the 704 patients, 347 had rheumatoid arthritis, 113 had psoriatic arthritis, and 87 had systemic lupus erythematosus. The rheumatic disease was treated in 484 patients using conventional DMARDs, most commonly methotrexate (n = 232) and hydroxychloroquine (n = 214); in 258 patients, the rheumatic disease was treated using biologic DMARDs, most frequently tumor necrosis factor inhibitors (n = 144).Use of outpatient treatments for COVID-19 in these patients increased in frequency over the course of the trial: 20/57 (35%) patients in the first week of the study received outpatient treatment, compared with 44/68 (65%) in the last full week of the study. Overall, 61% (426/704) of patients received outpatient treatment:307 patients were treated with oral nirmatrelvir-ritonavir.105 patients were treated with monoclonal antibodies.5 patients were treated with oral molnupiravir.3 patients were treated with remdesivir.6 patients were treated with combination treatments.The primary outcomes in the trial were severe COVID-19, defined as hospitalization or death within 30 days of infection, and COVID-19 rebound, defined as documentation of a negative SARS-CoV2 test after treatment, followed by a newly positive test. A total of 58 hospitalizations, including 3 deaths, occurred within 30 days of the COVID-19 index date: 9 patients (2.1%) among the 426 patients who received outpatient treatment required hospitalization, compared with 49 patients (17.6%) among the 278 patients who did not. One of the 3 deaths occurred among those who received treatment. Severe outcomes occurred in 4.8% of those whose COVID-19 infection was treated with monoclonal antibodies (n = 5) and in 1.3% of those treated with oral nirmatrelvir-ritonavir (n = 4), with 1 death. No severe COVID-19 occurred in those treated with molnupiravir, remdesivir, or combination treatment. Among the 27 unvaccinated patients, 2 (7.4%) had severe outcomes; neither had received outpatient treatments. Of the 58 patients with severe COVID-19 outcomes on primary analysis, 46 (79%) were considered by independent reviewers to have COVID-19 as the primary or partial reason for hospitalization, with 29 of them having COVID-19 pneumonia. Documented COVID-19 rebound occurred in 7.9% of patients with systemic autoimmune rheumatic disease who received oral outpatient treatment (n = 25/318). The exact mechanisms of COVID-19 rebound are unknown but might reflect incomplete viral eradication at the completion of oral SARS-CoV2 treatment. It’s possible that the underlying immunosuppression in these patients may play a role in the higher risk of COVID-19 rebound.These results should encourage clinicians to prescribe–and patients with these rheumatic diseases to seek–prompt outpatient SARS-CoV2 treatment. (Qianj, G., et al. (2023). Outcomes with and without outpatient SARS-CoV2 treatment for patients with COVID-19 and systemic autoimmune rheumatic diseases: A retrospective cohort study.  Lancet Rheumatol, 5 (3), E139–E150. Retrieved February 2023 from  https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(23)00006-1/fulltext )Released: February 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - January 2023
Interim Results Indicate that Emicizumab-kxwh Prevents Bleeding Episodes in Hemophilia AHemophilia A is an inherited disorder in which lack of intrinsic factor VIII leads to frequent bleeding into joints and muscles, resulting in chronic swelling, deformity, reduced mobility, and long-term joint damage. The World Federation of Hemophilia recommends early prophylaxis, but commonly, treatment is not initiated until after the first year of life because of the related high burden of care. The study design aims to address that by offering the parents options of dosage regimen and subcutaneous administration.READ MORE...Genentech released interim data from the HAVEN 7 study at the American Society of Hematology’s annual meeting in New Orleans in December. HAVEN 7 is a Phase III, multicenter, open-label study that evaluated the benefits of preventive treatment with emicizumab-kxwh, a factor IXa- and factor X-directed antibody, in previously untreated severe hemophilia A without factor VIII inhibitors. (A serious complication of treatment for hemophilia A is the development of inhibitors to factor VIII replacement therapies.) Hypothesizing that beginning treatment as early as possible could produce improved results, the study enrolled patients with severe hemophilia A, demonstrated by an intrinsic factor VIII level of less than 1%. The infants could begin treatment as early as birth to age 12 months, and were given emicizumab subcutaneously at 3 mg/kg once every 2 weeks for 52 weeks; after 1 year, parents could opt for their infants to continue with emicizumab treatment in three different dosage regimens: 1 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks.On interim analysis, emicizumab-kxwh achieved meaningful control of bleeding: 77.8% (n = 42) of treated infants had no bleeds that required treatment, and 42.6% (n = 23) had no incidents of bleeding at all. The report showed that a total of 77 bleeds occurred in 31 participants; 88.3% of those bleeds were a result of injury rather than being spontaneous bleeds. No spontaneous bleeds were serious enough to require treatment. The annualized bleeding rate at the time of this analysis was 0.4 for treated bleeds. The safety profile in these younger patients was consistent with the findings in previous studies, with no new safety issues noted and all reported adverse events were local injection-site reactions.These results are quite promising and suggest that treatment of hemophilia A with emicizumab can safely start at birth. Continued monitoring of these infants over the 7 years of follow-up should provide useful long-term data on joint health and safety.(Genentech. (2022, December 10). Interim data from Phase III study presented at ASH 2022 show Hemlibra (emicizumab-kxwh) achieved meaningful bleed control in infants from birth. [Press release]. Retrieved January 2023 fromhttps://www.gene.com/media/press-releases/14975/2022-12-10/interim-data-from-phase-iii-study-presen)Released: January 2023Nursing Drug Handbook© 2023 Wolters KluwerLSD Therapy Seen as Effective for AnxietyPsychedelics such as LSD [lysergic acid diethylamide] and psilocybin induce profound, acute mood alterations and mystical-type experiences, primarily by interacting with the serotonin 5HT2A receptor. Because of those effects on mood, they have been posited as an alternative treatment option for anxiety. Most research in the therapeutic potential of psychedelics used psilocybin, but a current study investigated the effects of LSD on anxiety, depression, and overall psychiatric symptomatology in patients with anxiety associated with life-threatening illnesses and in those with anxiety without life-threatening illness.READ MORE...The Swiss study, a multicenter, randomized, double-blind, placebo-controlled, crossover design, aimed to corroborate the findings of a small pilot study, in which patients who received LSD demonstrated trends toward reduction in anxiety associated with life-threatening illness. The trial also included patients with psychiatric anxiety disorders in the absence of life-threatening illness. In the crossover design, the patients underwent two 200-µg LSD sessions and two placebo sessions. All patients were intended to receive both LSD and placebo. To be included in the study, patients with life-threatening disorders had to meet the DSM-IV criteria for anxiety disorder or score at least 40 points on the state or trait scales of the Spielberger State-Trait Anxiety Inventory (STAI) at study inclusion. Those without life-threatening illnesses had to meet DSM-IV criteria for at least one anxiety disorder; elevated STAI scores were not sufficient for inclusion.The study involved a screening visit and two 24-week treatment periods per participant. Each treatment period consisted of two treatment sessions and five study visits, with treatment sessions separated by 6 weeks. Study visits occurred at baseline, between treatment sessions, and at 2, 8, and 16 weeks after the second treatment session, with the 16-week visit counting as the end-of-study visit. Results were analyzed for 42 participants, 20 patients who had a life-threatening illness and anxiety and 22 with anxiety disorder not associated with an illness.Use of LSD during two treatment sessions induced rapidand lasting reductions in anxiety, depression, and general psychiatric symptoms for up to 16 weeks. Effects were maximal at the 2-week study visit and were sustained up to 16 weeks. Least-square mean change for baseline in STAI-Global score at 16 weeks was –14.9 in the LSD group and +1.3 in the placebo group, for a significant difference in anxiety reduction. Similar effects were observed for ratings of comorbid depression: the difference on the Hamilton Depression Rating Scale, 21-item was –7.0 and on the Beck Depression Inventory was –6.1. Positive acute subjective drug effects and mystical-type experiences correlated with the long-term reductions in anxiety symptoms. Clinical response (30% or greater reduction in STAI-G scores) was seen in 65% (13/20) in the LSD group and in 9% (2/22) in the placebo group at any outcome visit.Transient, mild adverse effects were reported by 8 patients (19%) and one serious treatment-related adverse event (acute treatment anxiety and delusions) occurred. The serious effect was successfully treated with lorazepam and olanzapine, and the patient then received 100 µg at the second treatment session. In addition, in 3 patients, the dose in the second session was decreased because the response during the first session was considered too strong. The authors strongly recommend the use of two doses, as such a schedule allows the patient to become more familiar with the effects of psychedelics and potentially have better experiences in cases like these, where the first dose was challenging.No real blinding was possible in this study, because of the characteristic effects of LSD; in addition, due to the crossover design, patients who received LSD in the first treatment session had persistent therapeutic effects that continued into the second treatment period whether they received placebo or LSD. Also, both patients and therapists were highly motivated, which might be difficult to replicate in the general population. Larger trials will be needed to confirm these findings. (Holze, F., et al. (2023). Lysergic acid diethylamide-assisted therapy in patients with anxiety with and without a life-threatening illness: A randomized, double-blind, placebo-controlled phase II study. Biol Psychiatr, 93(3), 215-223. Retrieved January 2023 from https://www.biologicalpsychiatryjournal.com/article/S0006-3223(22)01553-0/fulltext)Released: January 2023Nursing Drug Handbook© 2023 Wolters KluwerRituximab for Connective Tissue Disease-Associated Interstitial Lung DiseaseManagement of interstitial lung disease (ILD) associated with connective tissue disease (CTD) has been challenging. International guidelines recommend IV cyclophosphamide for severe or progressive scleroderma-associated ILD, but its use is limited by adverse effects. Rituximab is often used as rescue therapy for treatment-refractory CTD-associated ILD but has not been studied in clinical trials. A report in The Lancet Respiratory Medicine described the findings of the first study to compare these two treatments for CTD-associated ILD.READ MORE...The RECITAL study is a randomized, double-blind, double-placebo, phase 2b trial that compared IV rituximab with IV cyclophosphamide for CTD-ILD, using a design that included a range of CTD diagnoses. Between December 2014 and March 2020, 145 participants were recruited from specialist ILD or rheumatology centers in the UK. Patients ages 18 to 80 (mean age, 56.6 years) with severe or progressive ILD related to scleroderma (n = 37), idiopathic inflammatory myositis (n = 44), or mixed connective tissue disease (n = 16) were randomized to IV rituximab (1,000 mg on day 0 and day 14, with placebo given every 4 weeks from week 4 to week 20; n = 51) or to IV cyclophosphamide (600 mg/m2 BSA every 4 weeks to week 20 with placebo given on day 14; n = 50).Improvement in lung function was measured in changes from baseline in forced vital capacity at 24 weeks; researchers found no significant differences between the two groups: The unadjusted mean increase in forced vital capacity at 24 weeks was 99 mL with cyclophosphamide and 97 mL with rituximab. Improvements were also seen in quality of life scores on various tools: quality of life scores on the St. George’s Respiratory Questionnaire, in which higher scores indicate more respiratory-related limitations, fell by 4.8 points at week 24 in the cyclophosphamide group and by 3.4 points in the rituximab group; on the King’s Brief Interstitial Lung Disease questionnaire, scores improved by 9.4 points in the cyclophosphamide group and by 8.8 points in the rituximab group at 24 weeks. Overall survival, progression-free survival, and time to treatment failure did not differ significantly between groups.Rituximab use was associated with a lower number of adverse events (445 vs. 646 with cyclophosphamide) and with a 13.3% reduction in concomitant corticosteroid use. Cyclophosphamide use has been limited by toxicity (nausea, GI upset, hematuria, and increased risk of gonadal failure and of bladder cancer). This trial offers evidence supporting rituximab use and demonstrating that it may be a safe alternative to cyclophosphamide in CTD-ILD patients. Future studies could examine its use as part of combination treatment for CTD-ILD patients. (Manfredi, A., et al. (2023). Rituximab for connective tissue disease-associated interstitial lung disease. Lancet Respir Med, 11(1), 3-4. Retrieved January 2023 from https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00356-3/fulltext?dgcid=raven_jbs_etoc_email; Maher, T. M., et al. (2023). Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): A double-blind, double-dummy, randomized, controlled, phase 2b trial. Lancet Respir Med, 11(1), 45-54. Retrieved January 2023 from https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00359-9/fulltext?dgcid=raven_jbs_etoc_feature_lanres#seccestitle10)Released: January 2023Nursing Drug Handbook© 2023 Wolters KluwerRituximab for Connective Tissue Disease-Associated Interstitial Lung DiseaseManagement of interstitial lung disease (ILD) associated with connective tissue disease (CTD) has been challenging. International guidelines recommend IV cyclophosphamide for severe or progressive scleroderma-associated ILD, but its use is limited by adverse effects. Rituximab is often used as rescue therapy for treatment-refractory CTD-associated ILD but has not been studied in clinical trials. A report in The Lancet Respiratory Medicine described the findings of the first study to compare these two treatments for CTD-associated ILD.The RECITAL study is a randomized, double-blind, double-placebo, phase 2b trial that compared IV rituximab with IV cyclophosphamide for CTD-ILD, using a design that included a range of CTD diagnoses. Between December 2014 and March 2020, 145 participants were recruited from specialist ILD or rheumatology centers in the UK. Patients ages 18 to 80 (mean age, 56.6 years) with severe or progressive ILD related to scleroderma (n = 37), idiopathic inflammatory myositis (n = 44), or mixed connective tissue disease (n = 16) were randomized to IV rituximab (1,000 mg on day 0 and day 14, with placebo given every 4 weeks from week 4 to week 20; n = 51) or to IV cyclophosphamide (600 mg/m2 BSA every 4 weeks to week 20 with placebo given on day 14; n = 50).Improvement in lung function was measured in changes from baseline in forced vital capacity at 24 weeks; researchers found no significant differences between the two groups: The unadjusted mean increase in forced vital capacity at 24 weeks was 99 mL with cyclophosphamide and 97 mL with rituximab. Improvements were also seen in quality of life scores on various tools: quality of life scores on the St. George’s Respiratory Questionnaire, in which higher scores indicate more respiratory-related limitations, fell by 4.8 points at week 24 in the cyclophosphamide group and by 3.4 points in the rituximab group; on the King’s Brief Interstitial Lung Disease questionnaire, scores improved by 9.4 points in the cyclophosphamide group and by 8.8 points in the rituximab group at 24 weeks. Overall survival, progression-free survival, and time to treatment failure did not differ significantly between groups.Rituximab use was associated with a lower number of adverse events (445 vs. 646 with cyclophosphamide) and with a 13.3% reduction in concomitant corticosteroid use. Cyclophosphamide use has been limited by toxicity (nausea, GI upset, hematuria, and increased risk of gonadal failure and of bladder cancer). This trial offers evidence supporting rituximab use and demonstrating that it may be a safe alternative to cyclophosphamide in CTD-ILD patients. Future studies could examine its use as part of combination treatment for CTD-ILD patients. (Manfredi, A., et al. (2023). Rituximab for connective tissue disease-associated interstitial lung disease. Lancet Respir Med, 11(1), 3-4. Retrieved January 2023 from https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00356-3/fulltext?dgcid=raven_jbs_etoc_email; Maher, T. M., et al. (2023). Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): A double-blind, double-dummy, randomized, controlled, phase 2b trial. Lancet Respir Med, 11(1), 45-54. Retrieved January 2023 from https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00359-9/fulltext?dgcid=raven_jbs_etoc_feature_lanres#seccestitle10)Released: January 2023Nursing Drug Handbook© 2023 Wolters Kluwer
Drug News Abstracts - December 2022
A Small Risk of Interstitial Lung Disease Found with Use of Nonwarfarin AnticoagulantsA large nationwide population-based retrospective cohort study is the first to investigate the reported increased risk of interstitial lung disease (ILD) in patients with atrial fibrillation receiving direct oral anticoagulants (DOACs). These anticoagulants, which include the direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have been steadily displacing warfarin as the preferred anticoagulants for stroke prevention in atrial fibrillation. In clinical trials, cough and dyspnea were noted as adverse events, but ILD, a rare event, only became evident in large postmarketing studies and in case reports.READ MORE...Using the Taiwan National Health Insurance Research Database, the cohort study collected data on 106,044 patients (mean age, 73.4; 56.6% men) with nonvalvular atrial fibrillation (NVAF) and no preexisting chronic lung disease who received oral anticoagulation between June 2012 and December 2017; 60.9% of patients received one of the factor Xa inhibitors, 21.2% of patients received dabigatran, and 17.9% of patients received warfarin.After adjusting for patient differences at baseline, the factor Xa inhibitors as a group and individually were associated with a slightly greater risk of ILD compared to warfarin. The rate of incident ILD was 0.29 per 100 patient-years compared to 0.17 per 100 patient-years with warfarin (hazard ratio [HR], 1.54). Apixaban was associated with a rate of 0.35 per 100 patient-years, edoxaban with a rate of 0.37 per 100 patient-years, and rivaroxaban with a rate of 0.27 per 100 patient-years. Dabigatran was not associated with a greater risk of ILD on analysis. Concomitant use with amiodarone, which was frequent in this study, was associated with a higher risk of ILD regardless of the anticoagulant used; hazard ratios were as follows:· factor Xa inhibitors and amiodarone: HR, 1.41· dabigatran and amiodarone: HR, 1.62· warfarin and amiodarone: HR, 1.97Due to this study’s observational nature, it cannot definitively delineate the causal relationships it explores; additional research is needed to explore potential mechanisms. These results shouldn’t discourage clinicians from prescribing these drugs; numerous studies have demonstrated significant benefits with factor Xa inhibitors. On risk-benefit analysis, absolute increases in ILD with factor Xa inhibitors and dabigatran (-0.12 and -0.05 per 100 patient-years, respectively, vs. warfarin) were much smaller than the absolute reduction in ischemic stroke/systemic embolism (0.78 and 0.64 per 100 patient-years, respectively) and major bleeding (0.78 and 1.01 per 100 patient-years, respectively). The authors of the study recommend that clinicians vigilantly monitor any potential adverse lung outcomes associated with use of these drugs but note that there is no need to make any major changes to current practices. (Neale, T. (2022). Slight risk of interstitial lung disease seen with certain DOACs. tctMD. Retrieved November 2022 fromhttps://www.tctmd.com/news/slight-risk-interstitial-lung-disease-seen-certain-doacs; Chan, Y.-H., et al. (2022). Development of interstitial lung disease among patients with atrial fibrillation receiving oral anticoagulants in Taiwan. JAMA Netw Open, 5(11), e2443307. Retrieved November 2022 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2798871)Released: December 2022Nursing Drug Handbook© 2022 Wolters KluwerFDA Suggests Possibility of OTC NaloxoneThe nonselective opioid receptor antagonist naloxone is a critical component of the effort to combat the opioid crisis. Naloxone reverses the effects of the respiratory depression and sedation produced by opioids; when administered at the first signs of opioid overdose (OD), it can prevent opioid-related deaths.READ MORE...The FDA has announced that it’s taking steps to encourage the development of nonprescription formulations of naloxone as a component of its FDA Overdose Prevention Framework. That framework has four priorities:· Support the primary prevention of overdose by limiting initial prescription drug exposure and inappropriate long-term prescriptions.· Encourage harm reduction through innovative programs (such as this initiative) and education.· Advance development of evidence-based treatment for substance use disorders.· Protect public from unapproved, diverted, or counterfeit drugs that present risk of OD.Naloxone is currently available as a prescription drug in the United States in several dosage strengths and dosage forms. It was originally approved as an injectable product for use by hospital personnel and first responders in the treatment of opioid OD, but increasingly has been used by non-health-care professionals, as initiatives sought to put naloxone into the hands of those who might witness an overdose. Since 2014 the FDA has approved several prescription naloxone drug and device combination products for use in emergency treatment of a known or suspected opioid OD; these are known as “community use” naloxone. In addition, as of 2020, every U. S. state and the District of Columbia have naloxone access laws, with one or more of these features:· Third-party provisions that allow providers to prescribe naloxone to someone not directly at risk of OD; that is, to a caregiver or family member· Standing-order provisions that allow for nonpatient-specific prescriptions· Immunity from civil and criminal prosecutions for prescribers and dispensers.Taken together, community-based naloxone distribution programs and naloxone access laws help to illustrate the potential public health benefits of nonprescription naloxone use.On preliminary assessment, naloxone nasal spray up to 4 mg, as well as naloxone autoinjector for IM or subcut use up to 2 mg, are the best candidates for nonprescription use. These dosage forms are used by most consumers. As of 2021, more than 90% of sales of naloxone were for the nasal spray form, although it should be noted that these sales numbers don’t consider donations of naloxone to community-based distribution programs, which are primarily autoinjector products.Although the benefits of broader use of naloxone are significant, concerns exist with making them available over the counter, such as associated risks that include adverse drug effects and precipitation of opioid withdrawal syndrome. Monitoring for and mitigation of these risks are important. The FDA must ensure that any products developed for nonprescription use are appropriately designed to support the intended users’ needs, including the packaging and labeling, and meet the requirements of the Food Drug and Cosmetic Act, demonstrating a clinically meaningful difference from the prescription product. The FDA has asked for comments on this proposal. (FDA. (2022, November 15). FDA announces preliminary assessment that certain naloxone products have the potential to be safe and effective for over-the-counter use [Press release]. Retrieved November 2022 from https://www.fda.gov/news-events/press-announcements/fda-announces-preliminary-assessment-certain-naloxone-products-have-potential-be-safe-and-effective; Federal Register. (2022). Safety and effectiveness of certain naloxone hydrochloride drug products for nonprescription use; request for comments. Retrieved November 2022 from https://www.federalregister.gov/documents/2022/11/16/2022-24874/safety-and-effectiveness-of-certain-naloxone-hydrochloride-drug-products-for-nonprescription-use)Released: December 2022Nursing Drug Handbook© 2022 Wolters KluwerDo Real-Time Prescription Benefits Recommendations Lower Costs for Patients?The rise in U. S. health care costs, especially out-of-pocket costs for patients, is a major driver for efforts to increase medication price transparency. Real-time prescription benefits (RTPB), an electronic clinical decision support tool, provides patient- and medication-specific out-of-pocket information to prescribers at the point of use. A study published in JAMA Internal Medicine demonstrates that such medication price transparency solutions that make cost information available to the prescriber and recommend clinically appropriate alternatives can be an effective tool for generating savings.READ MORE...In the cluster randomized trial, conducted in medical practices in a large academic health system in New York City, all outpatient prescriptions written were randomly assigned to a control arm or to an RTPB recommendation arm. Analysis was limited to those medications for which the tool could recommend an available alternative. Of the 867,757 outpatient prescriptions written at the practices over the study period (January to July 2021), 4.2% (36,419) met the criteria for analysis.If a prescription was randomized to the RTPB recommendation arm, the RTPB system recommended alternatives: either a different medication, different length of prescription, and/or a different choice of pharmacy. The prescriber could then opt for either the initial order or one of the recommended options. Electronic health record data were used to analyze the effect of the intervention on prescribing, both on out-of-pocket patient costs as well as on use of mail order pharmacy or 90-day supplies. Out-of-pocket costs includes any copay, coinsurance, and deductibles the patient is responsible for under their prescription benefits plan.The average out-of-pocket costs for a 30-day supply of medication in the intervention arm was $39.90; in the control arm, it was $67.80. Use of the RTPB recommendations resulted in an adjusted 11.2% reduction in costs. Mail-order pharmacy use was 9.6% in the intervention group and 7.6% in the control group; no differences were found in rate of use of 90-day medication supply.It’s hoped that, by controlling the patient’s out-of-pocket costs, the RTPB system can improve adherence and health outcomes. Further research will be needed to understand the impact of the system on other outcomes, such as prescribing behavior and adherence. (Desai, S. M., et al. (2022). Effects of real-time prescription benefit recommendations on patient out-of-pocket costs: A cluster randomized clinical trial. JAMA Intern Med, 182(11), 1129–1137. Retrieved November 2022 from https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2796059)Released: December 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - November 2022
Amifampridine an Effective Treatment for Spinal Muscle AtrophySpinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations in the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein. The resulting deficiencies in the SMN protein lead to progressive lower motor neuron degeneration. Clinical severity in this disorder is variable, depending on the presence of the SMN2 gene, which can partially compensate for the SMN protein deficiency. Currently approved treatments for SMA target increasing SMN protein production by SMN2 (nusinersen, risdiplam) or reintroduce the SMN1 gene (gene therapy with onasemnogene abeparvovec).READ MORE...SMA-001, a phase 2, randomized, double-blind, placebo-controlled crossover study, explored a new avenue of treatment for SMA. Patients with SMA Type 3 commonly report fatigue and display a significant response on nerve stimulation studies, signs that suggest impaired neuromuscular junction (NMJ) transmission has a role in the disorder. Amifampridine, a voltage-dependent potassium channel blocker approved for treatment of Lambert-Eaton myasthenic syndrome, prolongs depolarization of the presynaptic NMJ terminal, enhancing neuromuscular transmission and muscle function.From January 2019 to September 2020, SMA-001 enrolled ambulatory patients with SMA Type 3 (able to walk unaided at least 30 meters) who had not received SMN-targeting therapies such as nusinersen. The study included 13 patients, 5 women and 8 men, mean age, 34.5 years. Patients first entered a run-in phase, in which amifampridine was individually titrated up to a maximal effective dose, but no higher than 80 mg/day. Then, those who achieved at least a 3-point improvement in the Hammersmith Functional Motor Score Expanded (HFMSE) were randomly assigned to amifampridine or placebo in a 28-day blinded crossover phase. Patients were assigned to amifampridine/placebo or placebo/amifampridine sequence, which they took for 2 weeks, then switched to the other, with no washout period. The dosage of amifampridine given in this crossover phase was that determined for each individual in the run-in phase. During weekly clinic visits, the HFSME was administered, as were a number of timed tests of motor skills and quality of life assessments.Statistically significant improvement in HFMSE was observed in patients taking amifampridine compared to placebo (mean difference, 0.792). This effect is small, but the fact that the HFMSE score had already improved by at least 3 points before randomization might explain that. However, no significant differences were observed in results of timed tests. In quality-of-life measures, statistically significant improvement was observed in the fatigue subscale, as well as a significant reduction in the expected treatment subscale, but for all other subscale scores, differences were nonsignificant. No serious adverse events were reported, and treatment adherence was high throughout the study.Results provided Class II evidence that amifampridine is safe and effective in treating ambulatory SMA Type 3 patients, demonstrating that fostering neuromuscular transmission can improve fatigability in these patients. The study findings were limited by the small sample size and the brevity of the study, since SMA Type 3 doesn’t typically progress rapidly. Larger, well-powered studies may better define the role of amifampridine as adjunctive treatment to SMN-enhancing treatments. (Bonanno, S., et al. (2022). Amifampridine safety and efficacy in spinal muscular atrophy ambulatory patients: A randomized, placebo-controlled, crossover phase 2 trial. J Neurol, 269, 5858–5867. Retrieved November 2022 from https://link.springer.com/article/10.1007/s00415-022-11231-7)Released: November 2022Nursing Drug Handbook© 2022 Wolters KluwerEtrolizumab for Crohn DiseaseResults of BERGAMOT, a randomized, double-blind, phase 3 study published in The Lancet Gastroenterology and Hepatology, demonstrated that maintenance treatment with etrolizumab, an antibody against β7 integrin, produced significantly higher rates of clinical remission in patients with moderate to severe Crohn disease. The study, conducted at 326 treatment centers worldwide, compared the safety and efficacy of etrolizumab, in two dosage strengths, with placebo as both induction and maintenance therapy.READ MORE...The study, conducted from March 2015 through September 2021, enrolled patients ages 18 to 80 with moderate to severe active Crohn disease, as defined by a Crohn Disease Activity Index (CDAI) score between 220 and 480, mean daily stool frequency score greater than or equal to 6, or daily stool frequency score greater than or equal to 3 and mean daily abdominal pain score greater than or equal to 1, and presence of active inflammation on ileocolonoscopy. The patients also had intolerance to or inadequate or no response to treatment with corticosteroids, immunosuppressants, or anti-TNF therapy within the past 5 years.BERGAMOT consisted of three induction cohorts (a placebo-controlled, double-blind exploratory cohort; an active cohort without placebo control; and a placebo-controlled, double-blind pivotal cohort) and a maintenance cohort. This report discusses the findings of cohort 3, in which 385 patients were randomly assigned to placebo (n = 97), 105 mg etrolizumab subcutaneously every 4 weeks (n = 143), or 210 mg etrolizumab subcutaneously every 4 weeks (n = 145). At week 14 of induction therapy, patients from all three cohorts who had a response to etrolizumab as measured by CDAI-70 were rerandomized to receive 105 mg etrolizumab or placebo as maintenance every 4 weeks for 52 weeks. As a result, 434 patients took part in the maintenance phase, 217 in the placebo arm, and 217 in the etrolizumab arm.The researchers determined the proportion of patients who entered clinical remission, defined as mean daily stool frequency less than or equal to 3 and mean daily abdominal pain less than or equal to 1, with no worsening, and the proportion who demonstrated endoscopic improvement, as shown by greater than or equal to 50% reduction in Simple Endoscopic Score for Crohn’s Disease (SES-CD). At week 14, 48 patients (33%) in the 210-mg induction group versus 28 patients (29%) in the placebo group were in clinical remission (adjusted treatment difference, 3.8%). Endoscopic improvement was seen in 40 patients (27%) in the 210-mg induction group vs. 21 patients (22%) in the placebo group (adjusted treatment difference, 5.8%). At week 66 of maintenance treatment, significantly higher proportions of patients receiving etrolizumab than those receiving placebo were in clinical remission: 76 patients (35%) in the etrolizumab maintenance group versus 52 patients (24%) on placebo (adjusted treatment difference, 11.3%). Significantly higher proportions of patients in the etrolizumab arm showed endoscopic improvement: 51 patients (24%) vs. 26 patients (12%) in the placebo arm (adjusted treatment difference, 11.5%).These findings demonstrate a significantly higher incidence of clinical remission and endoscopic improvement in patients with moderate to severe Crohn disease during the maintenance phase of treatment with etrolizumab, but not during induction. (Sandborn, W., et al. (2022). Etrolizumab as induction and maintenance therapy in patients with moderately to severe active Crohn’s disease (BERGAMOT): A randomized, placebo-controlled, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. Advance online publication. Retrieved November 2022 from https://www.thelancet.com/journals/langas/article/PIIS2468-1253(22)00303-X/fulltext)Released: November 2022Nursing Drug Handbook© 2022 Wolters KluwerAbnormal Menstrual Bleeding Associated with Anticoagulant for Acute VTEAbnormal uterine bleeding (AUB) is common among women of reproductive age treated with anticoagulants for acute venous thromboembolism (VTE), with a considerable negative impact on quality of life (QOL). The TEAM-VTE study, an international multicenter prospective cohort study in patients of reproductive age (18 to 50) diagnosed with acute VTE, was conducted at 12 hospitals across 8 European countries between August 2018 and September 2021. The study, published in the journal Blood, aimed to quantify the burden of AUB and to identify unmet clinical needs in patients receiving anticoagulant therapy.READ MORE...From August 2018 to March 2021, 98 patients with confirmed symptomatic first or recurrent VTE and active menstrual cycles, with a mean age of 34, were enrolled shortly after diagnosis of VTE (before the first day of the next menstrual cycle after VTE diagnosis or within 1 month of diagnosis) and were followed until discontinuation of anticoagulant treatment or 6 months, whichever came first. If AUB was discovered, a diagnostic workup was performed to rule out other causes of the bleeding. The patients were followed using various measures:· Menstrual blood loss for the last menstrual cycle before VTE and then for each cycle in the 3 to 6 months of follow-up was measured by pictorial blood loss assessment charts (PBAC), a validated self-reporting tool.· AUB-related QOL was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire (MBQ); these were available for 74 women.Patients were followed for recurrence of symptomatic VTE, any bleeding event other than AUB, and all-cause mortality, and were managed according to accepted guidelines and local preference. The researchers noted which anticoagulant was administered to treat the VTE in these patients; 78 were treated with oral direct factor Xa inhibitors (rivaroxaban, apixaban, edoxaban), 13 with vitamin K antagonists (warfarin) or low-molecular-weight heparins, and 7 with the direct thrombin inhibitor dabigatran.Overall, AUB as defined by one of three accepted measures (PBAC score greater than 100, PBAC score greater than 150, or self-report) occurred in 66% of patients at any time during the follow-up period; for 90% of them, this occurred within the first 2 months after VTE diagnosis. Among women without AUB before VTE based on retrospective PBAC scores (assessing blood loss during the last menstrual cycle before VTE diagnosis), new-onset AUB occurred in 60% (37% of the overall population of study) in those with retrospective PBAC less than or equal to 100, and in 63% (43% of the overall population) in those with retrospective PBAC less than or equal to 150.The median PBAC score increased during the first menstrual cycle compared with the retrospective PBAC (median PBAC before VTE was 35 and for first menstrual cycle was 95). After the first menstrual cycle, the amount of blood loss decreased gradually, followed by median PBAC scores that remained stable in the 2nd through 6th cycles at about twice the retrospective PBAC score. The observational design of the study and the low number of patients exposed to the different anticoagulants prevent drawing any definitive conclusions about differences among the oral anticoagulants; however, patients treated with dabigatran showed no increase in blood loss during the first cycle, in contrast to patients treated with either oral direct factor Xa inhibitors, vitamin K antagonists, or low-molecular-weight heparin.The overall QOL decreased significantly over time, with a mean increase in MBQ score of 5.1 points between baseline and cessation of anticoagulation or 6-month follow-up. On analysis, the decrease in QOL was observed only among those who had new-onset AUB, with mean difference in MBQ score of +9.2 points for those with new-onset AUB versus those without AUB and of +9.3 points for those with new-onset AUB versus those who had experienced AUB before VTE.These findings support the proposed association of incident AUB with anticoagulation and highlight the critical need to include assessment of AUB in daily practice. It should increase awareness and should lead to development of evidence-based strategies to routinely and adequately prevent and treat incident AUB in this setting. (de Jong, C. M. M., et al. (2022). Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism. Blood, 140(16), 1764–1773. Retrieved November 2022 from https://ashpublications.org/blood/article/140/16/1764/486115/Incidence-and-impact-of-anticoagulation-associated)Released: November 2022Nursing Drug Handbook© 2022 Wolters Kluwer
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