Effectiveness of Nirmatrelvir-Ritonavir for the Prevention of COVID-19-Related Hospitalization and Mortality: A Systematic Literature Review.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. AREAS OF UNCERTAINTY: As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. DATA SOURCES: We searched Embase and PubMed (December 22, 2021-March 31, 2023) and congress abstracts (December 1, 2021-December 31, 2022) for reports describing NMV/r effectiveness. THERAPEUTIC ADVANCES: In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%-92%) and longer-term (>30 days) (1%-61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. CONCLUSION: The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Economic burden of COVID-19 for employers and employees in the United States.

OBJECTIVE: Describe the economic burden of COVID-19 on employers and employees in the United States (US). METHODS: A targeted literature review was conducted to evaluate the impact of COVID-19 on US-based employers and employees in terms of healthcare resource utilization (HCRU), medical costs, and costs associated with work-loss. Searches were conducted in MEDLINE, Embase, and EconLit using a combination of disease terms, populations, and outcomes to identify articles published from January 2021 to November 4, 2022. As data from the employer perspective were lacking, additional literature related to influenza were included to contextualize the impact of COVID-19, as it shifts into an endemic state, within the existing respiratory illness landscape. RESULTS: A total of 41 articles were included in the literature review. Employer and employee perspectives were not well represented in the literature, and very few articles overlapped on any given outcome. HCRU, costs, and work impairment vary by community transmission levels, industry type, population demographics, telework ability, mitigation implementation measures, and company policies. Work-loss among COVID-19 cases were higher among the unvaccinated and in the week following diagnosis and for some, these continued for 6 months. HCRU is increased in those with COVID-19 and COVID-19-related HCRU can also continue for 6 months. CONCLUSIONS: COVID-19 continues to be a considerable burden to employers. The majority of COVID-19 cases impact working age adults. HCRU is mainly driven by outpatient visits, while direct costs are driven by hospitalization. Productivity loss is higher for unvaccinated individuals. An increased focus to support mitigation measures may minimize hospitalizations and work-loss. A data-driven approach to implementation of workplace policies, targeted communications, and access to timely and appropriate therapies for prevention and treatment may reduce health-related work-loss and associated cost burden.

In January 2020, the US government declared COVID-19 a public health emergency. This lasted until May 2023. To fight this health emergency, the US government provided free testing, vaccination, and treatment. Although the US government has declared the emergency over, COVID-19 continues to infect people. For people with private health insurance, costs associated with COVID-19 patient healthcare have now been transferred from the government to employers. In this study, we collected information from published scientific articles about the costs of COVID-19 for employers and workers in the US. We found that people who were not vaccinated against COVID-19 required more medical care and cost more than people who were vaccinated. In some cases, this trend lasted for as long as 6 months. This was mostly because of workers missing work, not working effectively while sick, and needing to be hospitalized. People who could work from home, whose companies had policies to prevent infections, and who took steps to avoid getting infected needed less medical care and missed work less often. This information may be used to help develop policies, communications, and guidance to prevent COVID-19 and limit its impact on employers and workers.

Cost-Effectiveness of Oral Nirmatrelvir/Ritonavir in Patients at High Risk for Progression to Severe COVID-19 in the United States.

OBJECTIVES: Nirmatrelvir/ritonavir (NMV/r) is an orally administered antiviral indicated for the outpatient treatment of patients with mild-to-moderate COVID-19 at high risk for disease progression to severe illness. We estimated the cost-effectiveness of NMV/r versus best supportive care for patients with mild-to-moderate COVID-19 at high risk for progression to severe illness from a US health sector perspective. METHODS: A cost-effectiveness model was developed using a short-term decision-tree (1 year) followed by a lifetime 2-state Markov model (alive and dead). The short-term decision-tree captured costs and outcomes associated with the primary infection and healthcare utilization; survivors of the short-term decision-tree were followed until death assuming US quality-adjusted life years (QALYs), adjusted in the short-term for survivors of mechanical ventilation. Baseline rate of hospitalization and NMV/r effectiveness were taken from an Omicron-era US real-world study. Remaining inputs were informed by previous COVID-19 studies and publicly available US sources. Sensitivity analyses were conducted for all model inputs to test the robustness of model results. RESULTS: NMV/r was found to decrease COVID-19 related hospitalizations (-0.027 per infected case) increase QALYs (+0.030), decrease hospitalization costs (-$1110), and increase total treatment cost (+$271), resulting in an incremental cost-effectiveness ratio of $8931/QALY. Results were most sensitive to baseline risk of hospitalization and NMV/r treatment effectiveness parameters. The probabilistic analysis indicated that NMV/r has a >99% probability of being cost-effective at a $100 000 willingness-to-pay threshold. CONCLUSIONS: NMV/r is cost-effective vs best supportive care for patients at high risk for severe COVID-19 from a US health sector perspective.

The impact of vaccination and outpatient treatment on the economic burden of Covid-19 in the United States omicron era: a systematic literature review.

AIMS: To identify and synthesize evidence regarding how coronavirus disease 2019 (COVID-19) interventions, including vaccines and outpatient treatments, have impacted healthcare resource use (HCRU) and costs in the United States (US) during the Omicron era. MATERIALS AND METHODS: A systematic literature review (SLR) was performed to identify articles published between 1 January 2021 and 10 March 2023 that assessed the impact of vaccination and outpatient treatment on costs and HCRU outcomes associated with COVID-19. Screening was performed by two independent researchers using predefined inclusion/exclusion criteria. RESULTS: Fifty-eight unique studies were included in the SLR, of which all reported HCRU outcomes, and one reported costs. Overall, there was a significant reduction in the risk of COVID-19-related hospitalization for patients who received an original monovalent primary series vaccine plus booster dose vs. no vaccination. Moreover, receipt of a booster vaccine was associated with a lower risk of hospitalization vs. primary series vaccination. Evidence also indicated a significantly reduced risk of hospitalizations among recipients of nirmatrelvir/ritonavir (NMV/r), remdesivir, sotrovimab, and molnupiravir compared to non-recipients. Treated and/or vaccinated patients also experienced reductions in intensive care unit (ICU) admissions, length of stay, and emergency department (ED)/urgent care clinic encounters. LIMITATIONS: The identified studies may not represent unique patient populations as many utilized the same regional/national data sources. Synthesis of the evidence was also limited by differences in populations, outcome definitions, and varying duration of follow-up across studies. Additionally, significant gaps, including HCRU associated with long COVID and various high-risk populations and cost data, were observed. CONCLUSIONS: Despite evidence gaps, findings from the SLR highlight the significant positive impact that vaccination and outpatient treatment have had on HCRU in the US, including periods of Omicron predominance. Continued research is needed to inform clinical and policy decision-making in the US as COVID-19 continues to evolve as an endemic disease.

Impact of COVID-19 Infection on Health-Related Quality of Life, Work Productivity and Activity Impairment by Symptom-Based Long COVID Status and Age in the US.

COVID-19 infection adversely impacts patients' wellbeing and daily lives. This survey-based study examined differences in patient-reported COVID-19 symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) among groups of patients defined based on age and symptom-based long COVID status. Symptomatic, COVID-19-positive US outpatients were recruited from 31 January-30 April 2022. Outcomes were collected via validated instruments at pre-COVID, Day 3, Week 1, Week 4, Month 3 and Month 6 following infection, with changes assessed from pre-COVID and between groups, adjusting for covariates. EQ-5D-5L HRQoL and WPAI scores declined in all groups, especially during the first week. Long COVID patients reported significantly higher symptoms burden and larger drops in HRQoL and WPAI scores than patients without long COVID. Their HRQoL and WPAI scores did not return to levels comparable to pre-COVID through Month 6, except for absenteeism. Patients without long COVID generally recovered between Week 4 and Month 3. Older (>50) and younger adults generally reported comparable symptoms burden and drops in HRQoL and WPAI scores. During the first week of infection, COVID-19-related health issues caused loss of 14 to 26 work hours across the groups. These data further knowledge regarding the differential impacts of COVID-19 on clinically relevant patient groups.

Place in Therapy of Cyclin-Dependent Kinase 4/6 Inhibitors in Breast Cancer: A Targeted Literature Review.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are the preferred regimen for patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer. However, the optimal treatment sequencing for CDK4/6i with other available therapeutic options is unclear. We conducted a targeted literature review to identify the current evidence on CDK4/6i treatment patterns in patients with breast cancer. The search was initially conducted in October 2021 and subsequently updated in October 2022. Biomedical databases and gray literature were searched, and bibliographies of included reviews were screened for relevant studies. The search identified ten reviews published since 2021 and 87 clinical trials or observational studies published since 2015. The included reviews discussed CDK4/6i usage with or without endocrine therapy (ET) in first-line and second-line treatment for patients with HR+/HER2- advanced or metastatic breast cancer, followed by ET, chemotherapy, or targeted therapy with ET. Clinical studies reported similar treatment sequences consisting of ET, chemotherapy, or targeted therapy with ET prior to CDK4/6i with ET, followed by ET monotherapy, chemotherapy, targeted therapy with ET, or continued CDK4/6i with ET. Current evidence suggests CDK4/6i are effective for HR+/HER2- advanced or metastatic breast cancer in earlier lines of therapy. Efficacy of CDK4/6i as measured by progression-free survival and overall survival was similar within a line of therapy regardless of the type of prior therapy. Survival on different post-CDK4/6i treatments was also similar within the same line of therapy. Additional research is needed to investigate the optimal place in therapy of CDK4/6i and the sequencing of treatments following progression on CDK4/6i.

Palbociclib Adherence and Persistence in Patients with Hormone Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Metastatic Breast Cancer.

Purpose: To assess adherence and persistence with palbociclib therapy in patients with HR+/HER2- metastatic breast cancer (mBC) in a US real-world setting. Methods: This retrospective study evaluated palbociclib dosing, adherence, and persistence using commercial and Medicare Advantage with Part D claims data from the Optum Research Database. Adult patients with mBC who had continuous enrollment 12 months prior to mBC diagnosis and initiated first-line palbociclib with aromatase inhibitor (AI) or fulvestrant between 02/03/2015 and 12/31/2019 were included. Demographic and clinical characteristics, palbociclib dosing and dose changes, adherence (medication possession ratio [MPR]), and persistence were measured. Adjusted logistic and Cox regression models were used to examine demographic and clinical factors associated with adherence and discontinuation. Results: Patients (n = 1066) with a mean age of 66 years were included; 76.1% received first-line palbociclib+AI and 23.9% palbociclib+fulvestrant. Most patients (85.7%) initiated palbociclib at 125 mg/day. Of the 34.0% of patients with a dose reduction, 82.6% reduced from 125 to 100 mg/day. Overall, 80.0% of patients were adherent (MPR), and 38.3% discontinued palbociclib during a mean (SD) follow-up of 16.0 (11.2) and 17.4 (13.4) months, for palbociclib+fulvestrant and palbociclib+AI, respectively. Annual income below $75,000 was significantly associated with poor adherence. Older age (age 65-74 years (hazard ratio [HR] 1.57, 95% CI, 1.06, 2.33), age ≥75 years (HR 1.61, 95% CI: 1.08, 2.41)) and bone-only metastatic disease (HR 1.37, 95% CI, 1.06, 1.76) were significantly associated with palbociclib discontinuation. Conclusion: In this real-world study, >85% of patients started palbociclib at 125 mg/day and 1 in 3 had dose reductions during the follow-up. Patients were generally adherent and persistent with palbociclib. Older age, bone-only disease, and low-income levels were associated with early discontinuation or non-adherence. Further studies are needed to understand the associations of clinical and economic outcomes with palbociclib adherence and persistence.