Comparative Effectiveness of Baricitinib Versus Tocilizumab in Hospitalized Patients With COVID-19: A Retrospective Cohort Study of the National Covid Collaborative.

OBJECTIVES: COVID-19 treatment guidelines recommend baricitinib or tocilizumab for the management of hospitalized patients with COVID-19. We compared the effectiveness of baricitinib vs. tocilizumab on mortality and clinical outcomes among hospitalized patients with COVID-19. DESIGN: Multicenter, retrospective, propensity-weighted cohort study using a target trial emulation approach. SETTING: The National COVID Cohort Collaborative (N3C), which is the largest electronic health records data on COVID-19 in the United States. The setting included 75 hospitals. PATIENTS: Adults who were hospitalized for COVID-19. INTERVENTIONS: Newly initiated on baricitinib or tocilizumab. MEASUREMENTS AND MAIN RESULTS: Our primary outcome was 28-day mortality. We used propensity scores with inverse probability of treatment weights (IPTWs) to control bias and confounding while comparing treatments. Among 10,661 individuals included in the study, 6,229 (58.4%) received baricitinib and 4,432 (41.6%) tocilizumab. Overall, the mean age of the cohort was 60.0 ± 15.1 years, 6429 (60.3%) were male, and 19.2% received invasive mechanical ventilation. After IPTW adjustment, baricitinib use was associated with lower 28-day mortality (odds ratio [OR], 0.91; 95% CI, 0.85-0.98) and hospital (OR, 0.88; 95% CI, 0.82-0.94) mortality compared with tocilizumab. Baricitinib was also associated with shorter hospital length of stay (incident rate ratio, 0.92; 95% CI, 0.90-0.94) and lower rates of hospital-acquired infections (OR, 0.86; 95% CI, 0.75-0.99), although no difference in ICU length of stay was noted between the two groups. CONCLUSIONS: In this large, diverse cohort of U.S. hospitalized adults with COVID-19, baricitinib was associated with significantly lower 28-day mortality, hospital mortality, shorter hospital length of stay, and less hospital-acquired infections compared with tocilizumab.

Nirmatrelvir/Ritonavir (Paxlovid) Use Among Individuals at Risk of Severe COVID-19: An Analysis of the National COVID Cohort Collaborative (N3C).

PURPOSE: Paxlovid is effective in reducing COVID-19 hospitalization and mortality. This study characterized Paxlovid use and evaluated racial/ethnic disparities over time among community-dwelling adults at high risk of progression to severe COVID-19 disease. METHODS: This retrospective cohort study used the National COVID Cohort Collaborative (N3C) data and included individuals aged 18 years or older diagnosed with COVID-19 between January 2022 and December 2023. The study cohort included nonhospitalized individuals who were at high risk of COVID-19 progression, and selected the first COVID-19 episode in each quarter, including reinfection episodes. Paxlovid use was defined as receiving Paxlovid within ±5 days of a COVID-19 diagnosis. We used descriptive statistics to characterize Paxlovid use overall and by calendar quarter and race/ethnicity. We used a generalized estimating equations (GEE) models to quantify the association of race/ethnicity with Paxlovid use controlling for age, gender, and clinical characteristics. RESULTS: Among 1 264 215 individuals at high risk of disease progression (1 404 607 episodes), Paxlovid use increased from 1.2% in January-March 2022 to 35.1% in October-December 2023. Paxlovid use was more common among non-Hispanic White individuals (23.9%) than non-Hispanic Black (16.5%) and Latinx/e (16.7%) patients. After adjusting age, gender, and clinical characteristics, Paxlovid use was less likely among non-Hispanic Black (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.68-0.70) and Latinx/e (OR 0.72, CI 0.71-0.73) patients than non-Hispanic White patients. CONCLUSIONS: Among a large, diverse cohort of community-dwelling individuals with COVID-19, nearly two out of three eligible individuals did not receive Paxlovid, and minoritized racial/ethnic groups were less likely to use Paxlovid than their non-Hispanic White individuals.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants vs Warfarin among Nursing Home Residents with Atrial Fibrillation: A Retrospective Cohort Study.

OBJECTIVE: Residents of nursing homes are usually excluded from clinical trials, including trials to assess treatments for common conditions such as nonvalvular atrial fibrillation (NVAF). We aimed to quantify the real-world comparative safety and effectiveness of direct-acting oral anticoagulants (DOACs) vs warfarin among nursing home residents with NVAF. DESIGN: Retrospective cohort study using 100% national Minimum Data Set and linked Medicare claims from January 2011 through December 2018. SETTING AND PARTICIPANTS: Long-term care nursing home residents aged ≥66 years enrolled in fee-for-service Medicare. We included individuals diagnosed with NVAF newly initiating oral anticoagulants. METHODS: We identified exposure to DOACs (apixaban, dabigatran, rivaroxaban, and edoxaban) vs warfarin. Outcomes were hospitalization for ischemic stroke/systemic embolism, major bleeding, pneumonia (negative control outcome), and all-cause death. We used inverse probability of treatment weighting competing risk regression models for clinical outcomes and Cox proportional hazards regression for all-cause death. RESULTS: Of 38,983 individuals newly initiating anticoagulants, 19,366 (49.7%) initiated DOACs and 19,617 (50.3%) initiated warfarin. In the inverse probability of treatment weighting analysis, compared with warfarin, there was no statistically significant association between DOAC use and ischemic stroke/systemic embolism [4.5 vs 4.7 events per 100 person-years; adjusted hazard ratio (aHR), 0.94; 95% CI, 0.84-1.05] or major bleeding (12.6 vs 12.4 events per 100 person-years; aHR, 1.03; 95% CI, 0.96-1.10). DOACs use was associated with a modest but statistically significant lower risk of all-cause death (48.1 vs 49.0 events per 100 person-years; IPTW analysis aHR, 0.95; 95% CI, 0.91-0.98). CONCLUSIONS AND IMPLICATIONS: Among nursing home residents with NVAF, DOACs and warfarin were associated with a similar risk of ischemic stroke/systemic embolism and major bleeding. However, the use of DOACs was associated with a slightly reduced risk of all-cause mortality.

Potential drug-drug interactions among U.S. adults treated with nirmatrelvir/ritonavir: A cross-sectional study of the National Covid Cohort Collaborative (N3C).

STUDY OBJECTIVE: To estimate the prevalence of potential moderate to severe drug-drug interactions (DDIs) involving nirmatrelvir/ritonavir, identify interacting medications, and evaluate risk factors associated with potential DDIs. DESIGN: Cross-sectional study. DATA SOURCE: Electronic health records from the National COVID Cohort Collaborative Enclave, one of the largest COVID-19 data resources in the United States. PATIENTS: Outpatients aged ≥18 years and started nirmatrelvir/ritonavir between December 23, 2021 and March 31, 2022. INTERVENTION: Nirmatrelvir/ritonavir. MEASUREMENTS: The outcome is potential moderate to severe DDIs, defined as starting interacting medications reported by National Institutes of Health 30 days before or 10 days after starting nirmatrelvir/ritonavir. MAIN RESULTS: Of 3214 outpatients who started nirmatrelvir/ritonavir, the mean age was 56.8 ± 17.1 years, 39.5% were male, and 65.8% were non-Hispanic white. Overall, 521 (16.2%) were potentially exposed to at least one moderate to severe DDI, most commonly to atorvastatin (19.2% of all DDIs), hydrocodone (14.0%), or oxycodone (14.0%). After adjustment for covariates, potential DDIs were more likely among individuals who were older (odds ratio [OR] 1.16 per 10-year increase, 95% confidence interval [CI] 1.08-1.25), male (OR 1.36, CI 1.09-1.71), smokers (OR 1.38, CI 1.10-1.73), on more co-medications (OR 1.35, CI 1.31-1.39), and with a history of solid organ transplant (OR 3.63, CI 2.05-6.45). CONCLUSIONS: One in six of individuals receiving nirmatrelvir/ritonavir were at risk of a potential moderate or severe DDI, underscoring the importance of clinical and pharmacy systems to mitigate such risks.

Effect of Nirmatrelvir/Ritonavir (Paxlovid) on Hospitalization among Adults with COVID-19: an EHR-based Target Trial Emulation from N3C.

This study leverages electronic health record data in the National COVID Cohort Collaborative's (N3C) repository to investigate disparities in Paxlovid treatment and to emulate a target trial assessing its effectiveness in reducing COVID-19 hospitalization rates. From an eligible population of 632,822 COVID-19 patients seen at 33 clinical sites across the United States between December 23, 2021 and December 31, 2022, patients were matched across observed treatment groups, yielding an analytical sample of 410,642 patients. We estimate a 65% reduced odds of hospitalization among Paxlovid-treated patients within a 28-day follow-up period, and this effect did not vary by patient vaccination status. Notably, we observe disparities in Paxlovid treatment, with lower rates among Black and Hispanic or Latino patients, and within socially vulnerable communities. Ours is the largest study of Paxlovid's real-world effectiveness to date, and our primary findings are consistent with previous randomized control trials and real-world studies.