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The ability to provide early antiviral treatment to prevent progression of the disease is hampered by the difficulties in detecting COVID-19 and in predicting which infected individuals will become symptomatic. This remains a major challenge to management of the pandemic, as some persons who appear to have few risk factors have been known to develop serious, even fatal, infections.

The FDA has issued emergency use authorization for two monoclonal antibody (MAb) combinations—casirivimab + imdevimab and bamlanivimab + etesevimab—for patients with mild to moderate COVID-19. Research shows that these treatments are most effective in those patients who are slow to mount a SARS-CoV2-specific immune response. When given early in the course of symptomatic infection, these MAb regimens demonstrate both reductions in the SARS-CoV2 detected on polymerase chain reaction and in the risk of more severe illness. But timely use of MAbs is difficult, given the problems with obtaining testing results in many populations.

The IV administration route for MAbs also presents a barrier to their use in outpatients. Research is ongoing into developing agents that can be administered by more user-friendly routes, including oral and inhaled agents. The Centers for Disease Control and Prevention’s ACTIV-2 study is part of ongoing efforts to develop antiviral agents that are easier to administer, and thus can be used in the outpatient setting; these agents include:

· AZD8895 and AZD1061, a MAb combination that is in phase 2 studies and is being examined in both IV and IM formulations

· Camostat mesylate, an oral serine protease inhibitor that blocks entry of the virus into cells

· Interferon beta is an inhaled formulation delivered by nebulizer that is also in phase 2.

A final emerging consideration in development of antiviral treatments for early COVID-19 infection is any interaction between these treatments and the vaccines. COVID-19 in a person who is fully vaccinated suggests either an inadequate immune response or infection with a variant. The struggle to contain this outbreak continues. (Cohen, M. S., et al. (2021). Outpatient treatment of SARS-CoV-2 infection to prevent COVID-19 progression. Clin Infect Dis. Advance online publication. Retrieved June 2021 from https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab494/6287650)

Released: July 2021

Nursing Drug Handbook

© 2021 Wolters Kluwer

The study collected data from an Italian health care utilization database and included 24,097 patients who were taking statins, antihypertensives, antidiabetic agents, and antiplatelets. Using the Multisource Comorbidity Score (MCS), an index of clinical status based on the presence of conditions derived from inpatient diagnostic information and outpatient drug prescriptions, 11.7% of these patients were considered to have a “severe” clinical profile. After approximately 2 ½ years of follow-up, 9,204 patients (31.7%) discontinued taking statins, including 5,819 patients who stopped statins before discontinuing other drug therapy. The researchers matched 4,010 patients who stopped statins alone (discontinuing group) with 4,010 patients who maintained adherence to all four drug classes (maintenance group) and then followed both groups to estimate the hazard of negative outcomes. The discontinuing group was 60% men, with a mean age of 76.5 years, and 12.6% had MCS scores of 4 to 5. In the maintenance group, 61.7% were men, with a mean age of 76.1 years, and 12.6% had MCS scores of 4 to 5. Compared with the maintenance group, the discontinuing group had an increased risk of hospital admissions for heart failure or any CV outcome, death from any cause, and emergency admissions for any cause. After a mean follow-up of 20.6 months and 20.4 months, respectively, for patients who discontinued and maintained statins, the results were as follows:

· Hospital admissions for heart failure: 408 vs. 337 events, with an incidence rate of 64 per 1,000 patient-years vs. 51.5 per 1,000 patient-years

· Hospital admissions for ischemic heart disease: 439 vs. 413 events, with an incidence rate of 69.7 per 1,000 patient-years vs. 64.6 per 1,000 patient-years

· Deaths from any cause: 528 vs. 463 events, with an incidence rate of 77.5 per 1,000 patient-years vs. 67.4 per 1,000 patient-years

· Emergency department (ED) admissions for any cause: 2,209 vs. 2,055 events, with an incidence rate of 506.2 per 1,000 patient-years vs. 449.8 per 1,000 patient-years.

Stopping statins was associated with a 12% higher risk of ED admissions for any cause, a 24% higher risk of heart failure, and a 15% higher risk of death from any cause. But the simplification of the patient’s medication regimen didn’t generate a significant reduction in ED access for neurologic causes, a proxy for episodes of delirium.

This study was limited by its design, in which adherence to medication was determined by prescriptions rather than actual use. In addition, researchers didn’t know why prescriptions were discontinued. It’s possible that the patients who discontinued were not following other health guidelines or effectively managing their CV risk factors. But some discontinuations could be due to adverse drug effects, perceived adverse effects, or to a physician’s judgment that the patient is low risk. Further research is necessary to understand these findings. (O’Riordan, M. (2021). Stopping statins ups CVD and mortality risks in pill-burdened seniors. TCTMD. Retrieved June 2021 from https://www.tctmd.com/news/stopping-statins-ups-cvd-and-mortality-risks-pill-burdened-seniors; Rea, F., et al. (2021). Cardiovascular outcomes and mortality associated with discontinuing statins in older patients receiving polypharmacy. JAMA Netw Open. 4(6), Article e2113186. Retrieved June 2021 from https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2780952)

Released: July 2021

Nursing Drug Handbook

© 2021 Wolters Kluwer

CaMEO was a cross-sectional, longitudinal web-based survey of the U.S. population. From September 2012 to November 2013, data was collected on the clinical course of migraine, family burden, barriers to care, migraine type, and comorbidities. In patients who met criteria for migraine consistent with the International Classification for Headache Disorders (ICHD-3), this analysis evaluated the types of medications used to treat or prevent migraine and the frequency of their use, comorbidities, and the number of emergency department (ED) and urgent care visits.

Medication overuse headache (MOH) is defined by the ICHD-3 as headache occurring at least 15 days per month in individuals with preexisting headache disorder and regular overuse of acute medications for longer than 3 months. AMO in the ICHD-3 refers to taking medications for at least 10 days per month (or at least 15 days per month for simple analgesics). Of 16,789 CaMEO respondents with migraine, 2,975 (17.7%) met criteria for AMO; about 67.9% reported fewer than 15 monthly headache days and 49% reported fewer than 10 monthly headache days; this finding suggests that these respondents are taking their antimigraine medications on days when they don’t have a headache (perhaps in anticipation of a headache), or were taking multiple drugs to treat each headache, thus meeting the criteria for AMO.

The majority of respondents met the criteria for at least one medication class (2,753/2,975 [92.5%]), including at least 15 days’ use for simple analgesics like naproxen sodium, aspirin, ibuprofen, acetaminophen, and prescription, or at least 10 days’ use for ergotamines, triptans, opioids, or combination analgesics. A much smaller group met the criteria for AMO when their use of multiple medications was considered (222/2,975 [7.4%]); use of two or more simple analgesics cumulatively, but not any single medication, for more than 15 days; or use of two or more ergotamines, triptans, opioids, or combination analgesics, but not any single medication, for more than 10 days. Of the respondents with migraine, 14,936 (89%) reported using any acute medication; use of any OTC medication for headache was reported by 14,279 (85%) and of prescription medications was reported by 4,902 (29.2%).

Those with AMO were more likely than other respondents to have moderate to severe depression, anxiety, headache-related disability, and burden of disease between attacks. They also reported a higher incidence of ED and urgent care visits related to their headaches within the past 6 months. These findings illustrate the need for comprehensive migraine treatment plans that include improved acute treatment options as well as guideline-based preventive treatments, which include both nonpharmacologic and pharmacologic methods, to reduce frequency of AMO and the associated burden from possible MOH. (Schwedt, T. J., et al. (2021). Medication overuse and headache burden: Results from the CaMEO study. Neurol Clin Pract; 11(3): 216–222. Retrieved June 2021 from https://cp.neurology.org/content/11/3/216)

Released: July 2021

Nursing Drug Handbook

© 2021 Wolters Kluwer

The study enrolled 126 patients, of whom 124 had measurable disease at baseline and so were evaluated for their response to sotorasib. The patents were older than age 18, had locally advanced or metastatic NSCLC with the KRAS^G12C mutation, with disease progression after receipt of anti-PD-1 or anti-PD-L1 immunotherapy or platinum-based combination chemotherapy, ECOG performance status scale of 0 to 1, and measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST). Patients were enrolled from August 2019 to February 2020 and received at least one dose of sotorasib (960 mg/day PO).

Median duration of treatment was 5.5 months. As of the data cutoff date, 103 patients (81.7%) had discontinued treatment with sotorasib, 83 due to disease progression and 11 due to adverse effects. Dose reduction was seen in 26 patients (20.6%). Objective tumor response was observed in 46 patients (37.1%), 4 (3.2%) with a complete response and 42 (33.9%) with a partial response. Among those 46 patients, median time to response was 1.4 months and median duration of response was 11 months. As of data cutoff, 16 patients (34.7%) were continuing to receive sotorasib without disease progression. Median progression-free survival was 6.8 months, and median overall survival was 12.5 months. Treatment-related adverse events occurred in 88 patients (69.8%), including grade 3 events in 25 patients (19.8%) and grade 4 events in 1 patient (0.8%).

Further analysis evaluated the potential association between response to sotorasib therapy and these variables:

· baseline PD-L1 expression (86 patients assessed): objective response and tumor shrinkage were observed in 48% of patients in the PD-L1-negative group and in 42% of those in the PD-L1-positive group

· tumor mutational burden (84 patients assessed: objective response and tumor shrinkage were observed in 42% of patients with low tumor mutational burden and 40% of patients with high tumor mutational burden

· co-occurring genomic alterations (104 patients assessed): objective response was seen in 50% of patients with mutated STK11 and wild-type KEAP1, in 23% of those with mutations in both KEAP1 and STK11, and in 14% of those with mutated KEAP1 and wild-type STK11.

These data provide further evidence in support of the use of sotorasib in this population. A phase 3 trial comparing sotorasib to docetaxel in patients with previously treated, locally advanced, unresectable or metastatic NSCLC with KRAS^G12C mutation is underway. (Rosen, N. (2021). Finally, effective inhibitors of mutant KRAS. New Engl J Med; 384: 2447–2449. Retrieved June 2021 from https://www.nejm.org/doi/full/10.1056/NEJMe2107884; Skoulidis, F., et al. (2021). Sotorasib for lung cancers with KRAS p.G12C mutation. New Engl J Med; 384: 2371–2381. Retrieved June 2021 from https://www.nejm.org/doi/full/10.1056/NEJMoa2103695?query=featured_home)

Released: July 2021

Nursing Drug Handbook

© 2021 Wolters Kluwer