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Drug News Abstracts - April 2023


Dostarlimab Improves Survival in Endometrial Cancer

Endometrial 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.

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IV Methylprednisolone to Treat Pediatric Complications of SARS-CoV2 Infection

By 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.

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CDC Describes Monkeypox Vaccine Coverage in the United States

From 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.

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Data on Long-Term Safety and Efficacy of Risdiplam in Spinal Muscular Atrophy

New 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.

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Drug News Abstracts Archive


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
Drug News Abstracts - October 2022
Centanafadine in Adults with Attention Deficit Hyperactivity DisorderAttention deficit hyperactivity disorder (ADHD) likely results from dysregulation of the complex interplay of adrenergic and dopaminergic neurotransmission, resulting in deficits in executive function, reward processing, and attention. Centanafadine, a stimulant with nonstimulant characteristics that acts by inhibiting reuptake of norepinephrine, dopamine, and serotonin, is being investigated for use in adults with ADHD.READ MORE...A report in the Journal of Clinical Psychopharmacology describes the first large-scale studies to demonstrate the safety and efficacy of centanafadine in adults with ADHD. The two phase 3 randomized, double-blind, placebo-controlled, parallel-group studies were conducted from January 2019 through early 2020 in 45 clinical sites in the United States. To limit placebo effect, both studies were designed with a single-blind placebo run-in period, in which subjects who experienced an improvement in symptoms didn’t move on to randomization. The studies then randomized subjects to receive 200 mg/day of centanafadine sustained-release tablets (n = 149 study 1, 145 study 2); 400 mg/day of centanafadine sustained-release tablets (n = 149 study 1, 143 study 2); or placebo (n = 148 study 1, 142 study 2). Patients in both studies had moderate to severe ADHD at baseline (mean Adult ADHD Investigator Symptom Rating Scale [AISRS] total score, 38.7).Investigators determined change from baseline at day 42 in AISRS total score and in the Clinical Global Impression-Severity of Illness Scale (CGI-S). At day 42, statistically significant improvement in AISRS total score was achieved for both dosages compared with placebo in both studies. The AISRS total scores at day 42 were reduced by 25.5% in study 1 and 32.2% in study 2 for the 200-mg dose, by 24.6% in study 1 and 32.2% in study 2 for the 400-mg dose, compared to 17.7% in study 1 and 21.4% in study 2 for placebo. The differences in AISRS for centanafadine vs. placebo were as follows:• Study 1: -3.16 for 200 mg, -2.74 for 400 mg• Study 2: -4.01 for 200 mg, -4.42 for 400 mgThese differences were seen as early as day 28 and persisted throughout the study. Both dosages also produced statistically significant improvements in CGI-S score vs. placebo at day 42, as follows:• Study 1: -0.27 for 200 mg, -0.28 for 400 mg• Study 2: -0.33 for 200 mg, -0.28 for 400 mgThe overall rate of treatment-emergent adverse events was low, but there was a small increase noted with increases in centanafadine dose. The most common were headache and decreased appetite, which were considered mild or moderate.These trials were affected by the COVID-19 pandemic; study protocols had to be altered in late March 2020. As of March 23, study 1 had met its targets, so subjects still in treatment were withdrawn and continued to the safety follow-up phase, but study 2 had not yet met its completed-subject targets. All subjects who had not been randomized yet had treatment discontinued, and those who had been randomized continued to study completion, unless they tested positive for COVID. As a result, 348 subjects completed study 1 and 336 completed study 2. The most reported reason for discontinuation in study 1 was protocol deviation (5.6%), followed by adverse effects (4.1%) and withdrawal by subject (3.2%); in study 2 it was “other, not COVID-related” (6.6%), followed by withdrawal by subject (4.5%) and adverse effects (3.0%). Nine subjects in each study withdrew for reasons related to COVID-19.But despite these restrictions, the results still reached statistical significance. Future studies should determine long-term safety and should compare centanafadine to other available therapies for adults with ADHS. (Lenard, A., et al. (2022). Efficacy, safety, and tolerability of centanafadine sustained-release tablets in adults with attention-deficit/hyperactivity disorder: Results of 2 phase 3, randomized, double-blind, multicenter, placebo-controlled trials. J Clin Psychopharmacol. 42(5), 429–439. Retrieved October 2022 from https://journals.lww.com/psychopharmacology/Fulltext/2022/09000/Efficacy,_Safety,_and_Tolerability_of.2.aspx)Released: October 2022Nursing Drug Handbook© 2022 Wolters Kluwer Mepolizumab Significantly Reduced Asthma Exacerbations in Children at High RiskResearch has shown that therapies directed at the eosinophilic phenotype reduced asthma exacerbations in adults, but the effect on children was not as clear. Economically disadvantaged Black American and Hispanic American children are among those with the highest risk of morbidity and mortality associated with asthma, but there is scant data available on effective strategies in this vulnerable population. A new study demonstrates that adjunctive treatment with the humanized monoclonal antibody mepolizumab significantly reduced the number of asthma exacerbations in urban Black American and Hispanic American children. The study, MUPPITS-2 (Mechanisms Underlying Asthma Exacerbations Prevented and Persistent with Immune-based Therapy), was published in The Lancet.READ MORE...Between November 2017 and mid-March 2020, 290 children and adolescents were enrolled in the double-blind, placebo-controlled study, which was conducted at nine urban medical centers in the United States. The researchers enrolled children and adolescents ages 6 to 17 years who lived in socioeconomically disadvantaged neighborhoods and had exacerbation-prone asthma (that is, at least two exacerbations in the prior year) and blood eosinophil count of at least 150 cells/microliter. Median age of participants was 10 years; 55% were boys; approximately 70% were Black American and approximately 25% were Hispanic American. Median household income was $1,250 or less/month in 37% to 40% of participants, and between $1,251 and $2,500/month in 32% to 37% of participants. The children were randomly assigned to mepolizumab (n = 146) or to placebo (n = 144) injections once every 4 weeks for 52 weeks. The dosage of mepolizumab varied by age: 40 mg was given to those ages 6 to 11 years, and 100 mg was given to those ages 12 to 17 years. All participants also continued to receive guideline-based care for their asthma. The researchers aimed to determine whether adding mepolizumab to guideline-based care reduced the number of asthma exacerbations treated with systemic steroids during the 52 weeks of therapy.The average number of asthma exacerbations requiring treatment with systemic steroids fell significantly during the 52 weeks of the study. Among children and adolescents treated with mepolizumab, the number of exacerbations was 0.96; with placebo, it was 1.30. Relative decrease in these patients was 27%. Blood eosinophil levels were markedly reduced in patients who received mepolizumab, from a mean of more than 400 cells/microliter at baseline to less than 200 cells/microliter by week 8. These levels remained over 400 cells/microliter in placebo-treated children. Time to first asthma exacerbation wasn’t significantly different between the two groups, and no differences were shown in other asthma outcomes (lung function, change in disease severity). On patient global assessment, 84% of participants treated with mepolizumab and 89% of those treated with placebo self-reported clinically moderate or significant disease improvements. Study clinicians completed that same assessment and found improvement among 66% treated with mepolizumab and 71% treated with placebo.Researchers concluded that these findings highlighted the importance of evaluating treatment response in urban Black American and Hispanic American children, populations that are typically underrepresented in clinical trials. (Jackson, D. J., et al. (2022). Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): A randomised, double-blind, placebo-controlled, parallel-group trial. JAMA, 400(10351), P502–P511. Retrieved October 2022 fromhttps://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01198-9/fulltext; Slomski, A. (2022). Mepolizumab cuts asthma exacerbations among high-risk kidsJAMA, 328(12), 1171–1172. Retrieved October 2022 from https://jamanetwork.com/journals/jama/fullarticle/2796694)Released: October 2022Nursing Drug Handbook© 2022 Wolters Kluwer Obesity May Potentiate Risk of Thrombotic Events in Users of Oral ContraceptivesDespite the understanding that obesity and estrogen-containing contraceptives are independent risk factors for cardiovascular (CV) complications, a significant number of women with obesity continue to be prescribed these products for contraception. A review of current literature published in ESC Heart Failure, a journal from the European Society of Cardiology, provides evidence that obesity can potentiate CV risks—especially of venous thromboembolism (VTE)—in women of reproductive age taking combination oral contraceptives (COCs).READ MORE...The review examined the latest evidence and ongoing research on the CV impact of both obesity and contraceptive use, with a specific focus on clinical implications. An Italian review article cited a large population-based study showing that a body mass index (BMI) greater than 25 but less than 30 was associated with a 1.7-fold increased risk of VTE and a BMI above 30 was associated with a 2.4-fold increased risk. The study showed that when these subjects took COCs, risks increased to 12-fold in the group with BMI between 25 and 30 and to 24-fold in the group with BMI over 30 when compared to women who are nonobese not taking COCs. Another study was a meta-analysis that determined odds ratios (ORs) of VTE in women using COCs and showed that OR increased with BMI. When compared with COC users with BMI between 20 and 24.9, the odds of VTE in women using COC with BMI between 30 and 34.9 was 1.8 and in those with BMI of 35 or greater was 3.1. Another study showed that obesity has a greater impact on CV risk in women younger than age 40, the population that uses contraception; the risk of thrombosis in these individuals is 6.1 times higher than the risk in women who are nonobese. In addition, risk of drug-induced thrombosis can be dependent on the duration of drug therapy, a relevant issue with COCs, since users typically take them long-term.These findings should spur conversations between clinicians and young women early in their reproductive years to enable them to understand the risks and to make lifestyle and contraceptive choices that can minimize these risks. Women with a BMI over 30 taking COCs should be viewed as an at-risk population and should be advised to avoid other CV risk factors as primary prevention. In addition, clinicians should prioritize long-acting reversible methods of contraceptives such as intrauterine devices and subdermal implants, both for safety and effectiveness, in these patients. (McKeown, L. A. (2022). Obesity may boost thrombotic events in contraceptive users, review suggests. TCTMD. Retrieved October 2022 from https://www.tctmd.com/news/obesity-may-boost-thrombotic-events-contraceptive-users-review-suggests; Rosano, G. M. C., et al. (2022). Obesity and contraceptive use: Impact on CV risk. ESC Heart Failure. Advance online publication. Retrieved October 2022 from https://onlinelibrary.wiley.com/doi/full/10.1002/ehf2.14104)Released: October 2022Nursing Drug Handbook© 2022 Wolters Kluwer CDC Analysis Indicates Need for Improvements in Management of Children with Sickle Cell AnemiaAnalysis of Medicaid data on more than 3,300 children with sickle cell anemia demonstrated that many of these at-risk children are not receiving potentially lifesaving screening and treatment related to their disease. Sickle cell anemia is the most severe form of sickle cell disease, a disorder that results in misshapen, sticky red blood cells that break down easily, blocking blood flow and therefore resulting in impaired oxygenation of body tissues. The Centers for Disease Control and Prevention (CDC), which published this report, notes two health care measures are important in preventing complications in children with sickle cell anemia:READ MORE...Transcranial Doppler (TCD) ultrasound screening, which identifies children at risk for strokeHydroxyurea, a myelosuppressive agent, which reduces the occurrence of several complications of sickle cell anemia, including severe acute pain episodes and acute chest syndrome, which can result in lung injury and trouble breathingSickle cell anemia is a leading cause of stroke, but data showed that fewer than half of children with the disorder received the recommended stroke screening in 2019. The CDC’s analysis of 2019 Medicaid data showed that only 38% of children with sickle cell anemia ages 10 to 16 and 47% of those ages 2 to 9 had undergone TCD ultrasound screening. In addition, only 2 in 5 children ages 2 to 9 received hydroxyurea, the recommended treatment. The CDC study showed that in 2019, 53% of those ages 10 to 16 and 38% of those ages 2 to 9 were prescribed hydroxyurea. Stroke screening and hydroxyurea use were highest among children with high levels of health care use and those with prior complications.These results reflect the barriers to care of sickle cell patients, including structural racism. Patients lack access to providers with expertise in treating the disease and report having their symptoms dismissed or being stigmatized when they do engage with the health care system. In addition, both family members and providers hesitate to make use of hydroxyurea due to fear of potential side effects and uncertainty about its effectiveness.The CDC recommends that clinicians take steps to ensure that children with sickle cell anemia receive this important screening and this potentially lifesaving treatment. Among their recommendations:Increase TCD stroke screening by educating patients and families about the risk of stroke and the screening, identifying barriers to access (transportation, finances) and taking steps to alleviate them.Make stroke screening part of a single comprehensive visit when possible, and track TCD ultrasound screenings and follow-up in electronic health records.Encourage the patient and family to discuss with a health care provider the results of the TCD ultrasound screening and the next steps to take if the results indicate a greater risk of stroke.Become familiar with the guidelines on prescribing hydroxyurea and with studies showing the safety of the drug in these patients.To encourage adherence and follow-up, address barriers to patient access and incorporate reminders into the electronic health record.Educate the patient and family about hydroxyurea and the pros and cons of adherence to treatment protocol, and develop tools to help patients take hydroxyurea as directed.(CDC. Media Statements. (2022). Many children with sickle cell anemia not receiving lifesaving screening and treatment. Retrieved October 2022 from https://www.cdc.gov/media/releases/2022/s0920-vs-sickle-cell-anemia.html; CDC. Vital Signs. (2022). Preventing sickle cell complications in children. Retrieved October 2022 from https://www.cdc.gov/vitalsigns/sickle-cell-anemia/)Released: October 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - September 2022
Evening Dosing of Antihypertensive Not Superior to Morning DosingA randomized UK trial in more than 21,000 patients with hypertension has challenged the long-standing belief that evening doses of antihypertensive medications lead to better outcomes. Results of the trial TIME (Treatment In Morning vs. Evening), a large, prospective, randomized trial that tested whether evening doses of antihypertensives improved major CV outcomes compared with morning dosing, were presented at the European Society of Cardiology Congress in Barcelona.READ MORE...Adults taking antihypertensive medications in the UK who had a valid e-mail address were recruited and followed for more than 5 years. After signing up on the trial website, participants were randomized, 10,503 to evening dosing and 10,601 to morning dosing. Average age of patients was 65; 58% were men and 98% were white. Information on outcomes was obtained from e-mail contact with participants and through record linkages to national databases. Further data was gathered from family doctors and hospitals in the UK and was adjudicated by a blinded committee.The composite endpoint for the study was hospitalization for nonfatal MI, nonfatal stroke, or vascular death. This occurred at similar frequencies regardless of the time of medication administration: 362 participants (3.4%) in the evening dosing group and 390 participants (3.7%) in the morning dosing group experienced these outcomes, for an unadjusted hazard ratio (HR) of 0.95. Other outcomes also showed that neither time of antihypertensive dosing was superior to the other. These outcomes include:Nonfatal stroke: HR, 0.93Nonfatal MI: HR, 0.92CV death: HR, 1.1All-cause mortality: HR, 1.04During the presentation, researchers concluded that patients can take their regular antihypertensive medications at a time of day that is convenient and works for them. (Practical Cardiology. (2022). TIME study: No added benefit from nighttime dosing of blood pressure medications. Retrieved August 2022 from https://www.practicalcardiology.com/view/time-study-no-added-benefit-from-nighttime-dosing-of-blood-pressure-medications; European Society of Cardiology. (2022). Evening dosing of blood pressure medication not better than morning dosing. Press release. Retrieved August 2022 from https://www.escardio.org/The-ESC/Press-Office/Press-releases/Evening-dosing-of-blood-pressure-medication-not-better-than-morning-dosing) Released: September 2022Nursing Drug Handbook© 2022 Wolters KluwerCDC Report Details Safety of COVID-19 Booster Doses for Children Ages 5 to 11A report from the Centers for Disease Control and Prevention (CDC) published in MMWR detailed the findings of safety monitoring of COVID-19 vaccine booster doses administered to children ages 5 to 11. On May 17, 2022, the FDA authorized a booster dose of the Pfizer-BioNTech COVID-19 vaccine under Emergency Use Authorization for children ages 5 to 11 years, to be given 5 months after receipt of the second primary series dose. Approximately 650,000 booster doses were administered to individuals in this age group in the first 10 weeks of rollout (May 17 to July 31).READ MORE...Safety data were obtained from v-safe, a voluntary smartphone-based safety surveillance system established to monitor adverse events after COVID-19 vaccination, and from VAERS (Vaccine Adverse Event Reporting System), a national passive vaccine safety surveillance system comanaged by the CDC and FDA. Through v-safe, health surveys are sent daily to registrants during the first week after vaccine administration, with questions about potential local injection-site reactions and systemic reactions as well as health inputs. If parents indicate on the survey that they sought medical care for their child after vaccination, the CDC’s v-safe call center contacts them and encourages completion of a VAERS report. VAERS was developed to monitor adverse events after vaccination; it accepts reports from health care providers, vaccine manufacturers, and members of the public. Serious events that are included in the report include hospitalization, life-threatening illness, permanent disability, congenital anomalies/birth defects, or death.During those first 10 weeks, approximately 657,302 U.S. children received a third (booster) dose of the Pfizer-BioNTech vaccine; 3,249 reports were made to v-safe for children in this age group. Both local injection-site reactions (n = 2,224) and systemic reactions (n = 1,483) were reported; the prevalence of both was similar to that seen after the second dose of the vaccine:Local reactions: 68.5% booster, 68.0% second doseSystemic reactions: 45.6% booster, 45.8% second doseThe most frequently reported adverse events were injection-site pain (n = 2,166), fatigue (n = 938), and headache (n = 647); most were mild and were most frequently reported the day after vaccination. In the week after receiving the booster, 225 enrolled children were unable to attend school, and 392 were unable to complete daily activities. The inability to attend school was reported less frequently than after the second dose (6.9% vs. 10.0%), but inability to complete daily activities was reported more frequently (12.1% vs. 7.5%).VAERS received 581 reports of adverse events after receipt of the booster by children ages 5 to 11; 578 (99.5%) of these reports were considered nonserious. The most commonly reported events (71.1%) were vaccine administration errors (such as preparation errors, incorrect dose, and inappropriate age). Local and systemic reactions were common among the VAERS reports, but no reports of myocarditis or death were received. Only three serious reports were made to VAERS: new-onset diabetes 10 days after vaccination, facial swelling 3 days after vaccination, and pain, fatigue, and malaise 5 days after vaccination.These findings may change somewhat over time, as safety monitoring continues, more school-age children receive boosters, and as vaccine providers gain additional experience with pediatric doses of COVID-19 vaccines. Continued education of vaccine providers might reduce the errors reported to VAERS. (Hause, A. M., et al. (2022). Safety monitoring of Pfizer-BioNTech COVID-19 vaccine booster doses among children aged 5-11 years – United States, May 17 – July 31, 2022. MMWR, 71(33): 1047–1051. Retrieved August 2022 from https://www.cdc.gov/mmwr/volumes/71/wr/mm7133a3.htm) Released: September 2022Nursing Drug Handbook© 2022 Wolters KluwerOlokizumab Effectiveness Expands Treatment Options for Rheumatoid ArthritisA new drug for rheumatoid arthritis (RA) has been shown to be at least as effective as the current gold standard treatment. Currently, if a patient’s disease progresses on initial therapy with the folic acid antagonist methotrexate, combination therapy with the tumor necrosis inhibitor adalimumab plus methotrexate is administered. Olokizumab is a monoclonal antibody that targets IL-6, which is known to play a role in the inflammatory process and in the progression of joint damage in RA.READ MORE...CREDO2 (Clinical Rheumatoid Arthritis Development of Olokizumab) was a Phase III, double-blind, randomized, placebo- and active-controlled, international trial conducted from May 2016 through November 2019 at 209 sites worldwide. Results of the multicenter study, published in the New England Journal of Medicine, compared treatment with olokizumab plus methotrexate to placebo and to the gold standard, adalimumab plus methotrexate, testing for superiority to placebo and for noninferiority to adalimumab.The study randomly assigned patients with RA and inadequate response to initial methotrexate treatment to receive olokizumab 64 mg every 2 weeks (n = 464), olokizumab 64 mg every 4 weeks (n = 479), adalimumab 40 mg every 2 weeks (n = 462), or placebo (n = 243). All patients continued receiving methotrexate. Patients were followed to determine if they met the criteria for an American College of Rheumatology 20 (ACR20) response by week 12. Such a response entails at least 20% fewer tender or swollen joints and an improvement of at least 20% in 3 of 5 treatment domains:Patient’s global assessment of disease activityPatient’s assessment of painProvider’s global assessment of disease activityPatient function according to score on Health Assessment Question-Disability IndexC-reactive protein level.Results demonstrated that, in patients with RA who were receiving maintenance methotrexate, olokizumab was superior to placebo and noninferior to adalimumab in producing ACR20 response at week 12. The proportion of patients who reached ACR20 response at 12 weeks was 44.4% with placebo, 70.3% with olokizumab every 2 weeks, 71.4% with olokizumab every 4 weeks, and 66.9% with adalimumab. Both dosages of olokizumab were considered noninferior to adalimumab on this measure.The percentage of patients with a Disease Activity Score 28 of less than 3.2 (a measure of acute inflammation) at week 12 was 12.8% of those receiving placebo, 45.3% of those receiving olokizumab every 2 weeks, 45.7% of those receiving olokizumab every 4 weeks, and 38.3% of those receiving adalimumab. The percentage of patients who achieved remission, as assessed by Clinical Disease Activity Index score of 2.8 or less at week 24, was 41.4% with placebo, 11.2% with olokizumab every 2 weeks, 12.1% with olokizumab every 4 weeks, and 13.0% with adalimumab. Adverse events occurred in approximately 70% of patients and were most commonly infections that were mild to moderate in severity.These results offer another option for treatment for patients with RA, up to 25% of whom don’t respond well to current treatment options. Larger and longer trials are needed to further elucidate the safety and efficacy of olokizumab in RA. (Smolen, J. S., et al. (2022). Olokizumab versus placebo or adalimumab in rheumatoid arthritis. New Engl J Med, 387: 715–726. Retrieved August 2022 from https://www.nejm.org/doi/full/10.1056/NEJMoa2201302) Released: September 2022Nursing Drug Handbook© 2022 Wolters KluwerUpdated Recommendations for Statin Use for Primary Prevention of Cardiovascular DiseaseUpdated recommendations for use of statins as primary prevention of atherosclerotic cardiovascular disease (CVD) in adults have been published by the U.S. Preventive Services Task Force (USPSTF) in JAMA. These recommendations were based on review of evidence on the benefits and harms of statins for reducing CVD-related morbidity or mortality and all-cause mortality in adults age 40 and older without a previous history of CVD and no signs or symptoms of CVD who were considered at risk.READ MORE...In pooled analysis, statins were associated with a decreased risk of all-cause mortality (18 trials), relative risk (RR), 0.92; of fatal or nonfatal stroke (15 trials), RR, 0.78; of fatal or nonfatal MI (12 trials), RR, 0.67; and with a decreased risk of composite CV outcomes (15 trials), RR, 0.72. No significant harm was associated with statin use in these studies, suggesting a significant overall benefit to their use as primary prevention.Based on this analysis, USPSTF makes the following clinical recommendations:Clinicians should prescribe statins as preventive for CVD in adults ages 40 to 75 who have at least one risk factor for CVD and a 10-year CVD event risk of 10% or greater; the analysis showed with moderate certainty that use of statins in this population had at least a moderate net benefit.Clinicians can selectively offer statins to those ages 40 to 75 with at least one CVD risk factor and a 10-year CVD event risk between 7.5% and 10%, taking the patient’s values and preference into account, as well as the presence of factors not included in the original risk assessment; the analysis showed with moderate certainty that use of statins in this population had a smaller net benefit.Evidence is insufficient to determine how beneficial it would be to prescribe statins as primary prevention for CVD events and mortality in adults age 76 or older with no history of CVD. Such use would be at the discretion of the clinician, taking other factors into consideration.The analysis also demonstrates directions for research, including improving the accuracy of CVD risk prediction in all racial, ethnic, and socioeconomic groups, gaining a clearer picture of the benefits and harms of statins as primary prevention in older adults, and determining the efficacy and safety of long-term statin use in younger adults, as well as examining the effects of early versus delayed initiation of statin therapy for primary prevention of CVD disease. (US Preventive Services Task Force. Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force recommendation statement. (2022). JAMA, 328(8): 746-753. Retrieved August 2022 from https://jamanetwork.com/journals/jama/fullarticle/2795521) Released: September 2022Nursing Drug Handbook© 2022 Wolters Kluwer
Drug News Abstracts - August 2022
Need for Access to Contraception Still Unmet for Many WomenThe Family Planning 2020 Initiative set a goal of increasing the number of women using modern contraceptives by 120 million in priority countries. A new report in The Lancet estimates that this number increased by 69 million in these countries, which would fall 51 million short of that goal. In the study, part of the systematic analysis for the Global Burden of Disease Study 2019, higher rates of contraceptive coverage were linked with the availability of a diverse range of contraceptive choices. This study elucidates the major increases in contraceptive use and the reductions in unmet need that have occurred since 1980.READ MORE...Researchers examined 1,162 population-based surveys of contraceptive use by women of reproductive age (ages 15 to 49) who self-reported current use of contraceptives for family planning. Using regression analysis, they determined estimates of the contraceptive prevalence rate (CPR) and modern CPR (mCPR), whether the demand for contraception was satisfied, and the contraceptive method mix, and examined them in both partnered and unpartnered women in five age groups.Between 1970 and 2019, increases were observed in use of all contraceptives (CPR), increasing by 18.7 percentage points, and that of mCPR, by 20.1 percentage points. The demand satisfied increased by 24.3 percentage points. In 2019, the average CPR was 51.9%, average of mCPR was 47.7%, and demand satisfied was 79.1%, although there were considerable differences geographically.Women ages 15 to 24 accounted for 16.0% of total need but 26.5% of global unmet need. The lowest rate of demand satisfied was found in women ages 15 to 19 (64.8%), followed by those ages 20 to 24 (71.9%); 43.2 million women ages 15 to 24 had unmet needs for contraception in 2019. These lower rates of satisfied demand in young women are cause for concern because of the effects both on the women themselves and society in general. Use of contraception is associated with reductions in maternal and neonatal mortality due to the avoidance of unintended and adolescent pregnancies, and access to contraceptives supports pursuit of education and economic opportunities. To address these disparities, family planning programs must determine the accessibility and acceptance of existing methods in use by other women among this younger age group.The methods women used to meet their contraception needs differed by marital status, age, and region. Compared with partnered women of all ages, unpartnered women more commonly used oral contraceptive pills and condoms; long-acting reversible methods (such as, IUDs, contraceptive implants, or injections) tended to be used most by women ages 20 to 49, and older women were more likely to use female sterilization.The absence of contraceptives tailored to the needs of younger women might be one explanation for the unmet need in that population; for example, if female sterilization is the method most often available, it’s unlikely to appeal to young women who haven’t had children yet. (Haakenstad, A., et al. (2022). Measuring contraceptive method mix, prevalence, and demand satisfied by age and marital status in 204 countries and territories, 1970–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet, 400(10348), 295–327. Retrieved July 2022 from https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00936-9/fulltext#seccestitle210)Released: August 2022Nursing Drug Handbook© 2022 Wolters KluwerMacrolide Antibiotics May Be Associated with Hearing Loss in ChildrenMacrolides are one of the most used medications in children, with the most frequently prescribed being azithromycin, clarithromycin, and erythromycin. A retrospective case-control study published in JAMA Otolaryngology–Head and Neck Surgery attempted to determine whether that outpatient macrolide treatment was associated with pediatric sensorineural hearing loss. Past research has linked sensorineural hearing loss in adults to prior use of high-dose or IV macrolide treatment, but it hasn’t been studied in children.READ MORE...Using data from TRICARE, the health insurance system for U.S. uniformed service members and their families, the study analyzed 875 matched pairs of children, adolescents, and young adults with and without sensorineural hearing loss from records of outpatient encounters from October 2009 to September 2014. They were matched by age, sex, and time elapsed since the date of antibiotic prescription. Mean age was 5.7 years; patients were 62% male, and 66% non-Hispanic white. Multivariate logistic regression was used to compare the risk of prior macrolide exposure with penicillin exposure, adjusted for other risk factors and potential confounders.They found that compared with peers without hearing loss, pediatric patients with sensorineural hearing loss were more likely to have received a prescription for a macrolide antibiotic compared to one for penicillin (adjusted odds ratio [aOR], 1.31). The odds were significantly higher when more than 180 days had elapsed between antibiotic exposure and the patient’s testing and diagnosis of hearing loss (aOR, 1.79).Currently, 56% of pediatric sensorineural hearing loss is considered idiopathic; this study suggests that macrolides warrant further study as potential risk factors. The results could also guide practice by encouraging early recognition of sudden hearing loss after macrolide use, given the success rate of prompt hyperbaric oxygen treatment for these patients. (Lopilato, J. (2022). Kids’ hearing loss associated with common antibiotics. MedPage Today. Retrieved July 2022 from https://www.medpagetoday.com/pediatrics/generalpediatrics/99855; Dabekaussen, K. F., et al. (2022). Association of outpatient oral macrolide use with sensorineural hearing loss in children, adolescents, and young adults. JAMA Otolaryngol—Head Neck Cancer. Retrieved July 2022 from https://jamanetwork.com/journals/jamaotolaryngology/article-abstract/2794472?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF)Released: August 2022Nursing Drug Handbook© 2022 Wolters KluwerOntamalimab Showed Sustained Treatment Response in Crohn DiseaseIn a substantial number of patients with Crohn disease, nonresponse or loss of response to the approved treatments results in an unmet need for novel treatments with a good safety profile and more durable efficacy. OPERA-II, a multicenter, open-label phase 2 extension study, examined the long-term safety and efficacy of one of these treatments, ontamalimab, a fully human IgG monoclonal antibody against mucosal addressin cell adhesion molecule-1.READ MORE...All patients in the study had completed 12 weeks of treatment in OPERA, a phase 2, double-blind, placebo-controlled trial that examined three dosage strengths of ontamalimab (22.5 mg, 75 mg, or 225 mg) and compared clinical response and remission in 265 patients with Crohn disease, or had had a clinical response to a 225-mg dose of ontamalimab in another study, TOSCA, a 12-week, open-label study in which ontamalimab was given to 39 patients with active Crohn disease who had previously received immunosuppressants. In OPERA, clinical response and remission were observed in greater proportions of patients in the treatment group than with placebo, although these differences hadn’t reached statistical significance, and in TOSCA, 80% of treated patients had a clinical response and 77% were in clinical remission at week 12.Conducted from July 2011 through July 2016 in 81 centers in 15 countries worldwide, OPERA-II examined safety (adverse events and serious adverse events) and efficacy (clinical remission and response rates at weeks 24 and 72, the rate of relapse and time to relapse, the proportions of patients with changes in dosage, and proportion who discontinued by week 16) outcomes in patients with moderate to severe Crohn with a history of failed immunosuppressant therapy. Participants received ontamalimab at 75 mg every 4 weeks for 72 weeks, and then were followed up every 4 weeks for 24 weeks. Dosage could be decreased to 22.5 mg for intolerance or adverse events or increased to 225 mg in patients with inadequate response.Overall, 149 of 268 patients completed the study; 74 patients discontinued during the study period and another 45 during follow-up. The most common event leading to discontinuation was disease flare, in 19.8% of patients; 2 patients died, no patients required dosage reductions, and 157 had dosage escalations. Median time to dosage escalation was 28 weeks. Of the 68 patients who required dosage escalation by week 8, 13 subsequently discontinued the study by week 16. During the treatment period, 249 patients reported a total of 1,550 adverse events, of which 385 were considered treatment related. During the follow-up period, 133 patients experienced a total of 461 adverse events, of which 42 were treatment related.Rates of clinical remission of Crohn disease, defined as a score on the Harvey Bradshaw index (HBI) less than or equal to 5, was 48.1% at baseline, 47.8% at the end of week 24 of follow-up, and 37.3% at week 72. Of the 128 patients who were not in remission at baseline, 84 achieved remission during the study, with a median time to remission of 16.9 weeks. Similar results were seen in response, as measured by decreases in HBI greater than or equal to 3 points; at baseline the response rate was 63.1%, at week 24 it was 54.5%, and by week 72 was 42.5%. Of the 99 patients who hadn’t demonstrated clinical response at baseline, 68 did so during the study, with a median time to response of 13.9 weeks. In those who received the higher, 225-mg dose, the proportion of those in remission remained relatively stable from week 12 (31.8%) to week 72 (32.2%). Relapse was defined as an increase greater than or equal to 3 points in HBI score from the lowest HBI score measured, with a total HBI score greater than or equal to 8. Of the 226 patients who had experienced clinical response at any time during the study, 119 (52.7%) experienced relapse, with the median time to relapse of 67.4 weeks. (D’Haens, G. R., et al. (2022). Long-term safety and efficacy of the anti-mucosal addressin cell adhesion molecule-1 monoclonal antibody ontamalimab (SHP647) for the treatment of Crohn’s disease: The OPERA II study. Inflamm Bowel Dis, 28(7), 1034–1044. Retrieved July 2022 from https://academic.oup.com/ibdjournal/article/28/7/1034/6357026#363711481)Released: August 2022Nursing Drug Handbook© 2022 Wolters Kluwer
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