Disease Burden and Access to Biologic Therapy in Patients with Severe Asthma, 2017-2022: An Analysis of the International Severe Asthma Registry.

Introduction: Patients with severe asthma may be prescribed biologic therapies to improve disease control. The EVEREST study aimed to characterize the global disease burden of patients with severe asthma without access to biologics and those who have access but do not receive biologics, as well as the remaining unmet need despite use of these therapies. Methods: This was a historical cohort study of patients with severe asthma (aged ≥18 years) in the International Severe Asthma Registry receiving Global Initiative for Asthma (GINA) 2018 step 5 treatment, or with uncontrolled disease at GINA step 4. Prospective data on patient clinical characteristics, healthcare resource utilization, and medication use over a 12-month period between December 2017 and May 2022 were assessed for the following five groups: biologics accessible (omalizumab, mepolizumab, reslizumab, benralizumab, or dupilumab); biologics inaccessible; biologics accessible but not received; biologics accessible and received; and biologic recipients whose asthma remained suboptimally controlled. Results: Overall, 9587 patients from 21 countries were included. Among patients in the biologics accessible (n=5073), biologics inaccessible (n=3041), and biologics accessible but not received (n=382) groups, 41.4%, 18.7%, and 49.6% experienced at least two exacerbations, 11.5%, 10.5%, and 6.2% required at least one hospitalization, 47.9%, 54.6%, and 71.2% had uncontrolled asthma, and 23.9%, 8.6%, and 11.0% received long-term oral corticosteroids (LTOCS), respectively. Following biologic therapy, among patients who received biologics overall (n=2666) and among those whose asthma remained suboptimally controlled (n=1780), 19.1% and 23.0% experienced at least two exacerbations, 2.7% and 2.9% required at least one hospitalization, and 16.7% and 22.0% received LTOCS, respectively. Conclusion: There is a substantial disease burden in both patients without access to biologics and those with access who do not receive these therapies, although specific outcomes may vary between these groups. There also remains a high unmet need among biologic recipients, many of whom have a suboptimal response to treatment.

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

Exploring Definitions and Predictors of Severe Asthma Clinical Remission after Biologic Treatment in Adults.

Rationale: There is no consensus on criteria to include in an asthma remission definition in real life. Factors associated with achieving remission after biologic initiation remain poorly understood. Objectives: To quantify the proportion of adults with severe asthma achieving multidomain-defined remission after biologic initiation and identify prebiologic characteristics associated with achieving remission that may be used to predict it. Methods: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1 year before and after biologic initiation. A priori-defined remission cutoffs were: 0 exacerbations/yr, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted FEV1 ⩾ 80%. Remission was defined using two (exacerbations + LTOCS), three (+control or +lung function), and four of these domains. The association between prebiologic characteristics and postbiologic remission was assessed by multivariable analysis. Measurements and Main Results: A total of 50.2%, 33.5%, 25.8%, and 20.3% of patients met criteria for two-, three- (+control), three- (+lung function), and four-domain remission, respectively. The odds of achieving four-domain remission decreased by 15% for every additional 10 years of asthma duration (odds ratio, 0.85; 95% confidence interval, 0.73-1.00). The odds of remission increased in those with fewer exacerbations per year, lower LTOCS daily dose, better control, and better lung function before biologic initiation. Conclusions: One in five patients achieved four-domain remission within 1 year of biologic initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission after biologic treatment, indicating that biologic treatment should not be delayed if remission is the goal.

Benralizumab in Severe Eosinophilic Asthma and Chronic Rhinosinusitis with Nasal Polyps: The Real-World, Multi-Country RANS Observational Study.

Purpose: Real-world evidence of benralizumab effectiveness on nasal polyps (NP) and asthma outcomes in patients with severe eosinophilic asthma (SEA) and comorbid chronic rhinosinusitis with NP are limited. The objective of this study was to assess NP and asthma outcomes in benralizumab-treated patients with SEA and comorbid NP in a real-world setting. Patients and Methods: RANS was a retrospective, multi-country observational study (ClinicalTrials.gov: NCT05180357) using medical chart reviews of adults with SEA and comorbid NP. Total NP Score (NPS), SinoNasal Outcome Test-22 (SNOT-22) total score, annualized exacerbation rate (AER), and 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Control Test (ACT) scores during the 12 months pre-index (baseline) and post-index (follow-up) were measured. Clinically meaningful improvement from baseline following treatment, in terms of total NPS (≥1-point reduction), SNOT-22 total (≥8.9-point reduction), ACQ-6 (≥0.5-point reduction) or ACT (≥3-point increase) scores, were reported. Results: A total of 233 patients were included. Baseline mean (standard deviation [SD]) NPS and SNOT-22 total scores were 3.8 (2.4) and 47.5 (22.6), respectively. The mean change (95% confidence interval [CI]) from baseline was -1.2 (-1.7, -0.6) for NPS, and -19.8 (-23.6, -15.9) for SNOT-22. The AER (95% CI) was 1.2 (0.96, 1.41) at baseline and 0.2 (0.13, 0.28) at follow-up. Mean (SD) ACQ-6 and ACT scores were 1.6 (1.3) and 15.0 (5.2) at baseline and 0.8 (1.0) and 22.0 (3.9) at follow-up, respectively. The proportion of patients who achieved clinically meaningful improvements in NPS, SNOT-22 total, ACQ-6, and ACT scores was 49.1%, 67.6%, 56.6%, and 81.1%, respectively. Conclusion: In this real-world study, improvements in NP and asthma outcomes in patients with SEA and comorbid NP were observed during the 12 months following benralizumab initiation.

Prediction of treatment nonadherence among older adults with chronic obstructive pulmonary disease using Medicare real-world data.

BACKGROUND: Suboptimal maintenance medication (MM) adherence remains a clinical problem among Medicare beneficiaries with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To inform risk-based personalized decision-making, this study sought to develop and validate prediction models of nonadherence to COPD MMs for Medicare beneficiaries. METHODS: This was a retrospective cohort study of beneficiaries aged 65 years and older with COPD and inhaled MMs. Nonadherence (proportion of days covered < 0.8) was measured in 12 months following the first MM fill after COPD diagnosis. Logistic and least absolute shrinkage selector operator regressions were implemented, and area under the receiver operating characteristic curve (AUROC) evaluated model accuracy, as well as positive predictive values and negative predictive values. Our models evaluated different sets of predictors for two cohorts: those with an MM prescription before COPD diagnosis (prevalent users) and those without (new users). RESULTS: Among 16,157 prevalent and 40,279 new users of MMs, 11,271 (69.8%) and 34,009 (84.4%), respectively, were nonadherent. The best-performing logistic models achieved AUROCs of 0.8714 and 0.881, positive predictive values of 0.881 and 0.881, and negative predictive values of 0.559 and 0.578, respectively, for prevalent and new users. The least absolute shrinkage selector operator models had similar accuracy. Models with baseline-only predictors had average performance (AUROC < 0.72). The most important predictors were initial MM adherence, short-acting bronchodilator use, and asthma. CONCLUSIONS: To our knowledge, this study is the first to develop predictive models of nonadherence to COPD MMs. Generated models achieved good discrimination and underlined the importance of early adherence. Well-performed models can be useful for care decision-making and interventions to improve COPD medication adherence after the first critical few months following a treatment episode. DISCLOSURES: All authors declared no conflicts of interest.

Staffing and Protective Equipment Access Mitigated COVID-19 Penetration and Spread in US Nursing Homes During the Third Surge.

OBJECTIVES: During the last quarter of 2020-despite improved distribution of personal protective equipment (PPE) and knowledge of COVID-19 management-nursing homes experienced the greatest increases in cases and deaths since the pandemic's beginning. We sought to update COVID-19 estimates of cases, hospitalization, and mortality and to evaluate the association of potentially modifiable facility-level infection control factors on odds and magnitude of COVID-19 cases, hospitalizations, and deaths in nursing homes during the third surge of the pandemic. DESIGN: Cross-sectional analysis. SETTING AND PARTICIPANTS: Facility-level data from 13,156 US nursing home facilities. METHODS: Two series of multivariable logistic regression and generalized linear models to examine the association of infection control factors (personal protective equipment and staffing) on incidence and magnitude, respectively, of confirmed COVID-19 cases, hospitalizations, and deaths in nursing home residents reported in the last quarter of 2020. RESULTS: Nursing homes experienced steep increases in COVID-19 cases, hospitalizations, and deaths during the final quarter of 2020. Four-fifths (80.51%; n = 10,592) of facilities reported at least 1 COVID-19 case, 49.44% (n = 6504) reported at least 1 hospitalization, and 49.76% (n = 6546) reported at least 1 death during this third surge. N95 mask shortages were associated with increased odds of at least 1 COVID-19 case [odds ratio (OR) 1.21, 95% confidence interval (CI) 1.05-1.40] and hospitalization (1.26, 95% CI 1.13-1.40), as well as larger numbers of hospitalizations (1.11, 95% CI 1.02-1.20). Nursing aide shortages were associated with lower odds of at least 1 COVID-19 death (1.23, 95% CI 1.12-1.34) and higher hospitalizations (1.09, 95% CI 1.01-1.17). The number of nursing hours per resident per day was largely insignificant across all outcomes. Of note, smaller (<50-bed) and midsized (50- to 150-bed) facilities had lower odds yet higher magnitude of all COVID outcomes. Bed occupancy rates >75% increased odds of experiencing a COVID-19 case (1.48, 95% CI 1.35-1.62) or death (1.25, 95% CI 1.17-1.34). CONCLUSIONS AND IMPLICATIONS: Adequate staffing and PPE-along with reduced occupancy and smaller facilities-mitigate incidence and magnitude of COVID-19 cases and sequelae. Addressing shortcomings in these factors is critical to the prevention of infections and adverse health consequences of a next surge among vulnerable nursing home residents.

Prevalence and Newly Diagnosed Rates of Multimorbidity in Older Medicare Beneficiaries with COPD.

Few studies have quantified the multimorbidity burden in older adults with chronic obstructive pulmonary disease (COPD) using large and generalizable data. Such evidence is essential to inform evidence-based research, clinical care, and resource allocation. This retrospective cohort study used a nationally representative sample of Medicare beneficiaries aged 65 years or older with COPD and 1:1 matched (on age, sex, and race) non-COPD beneficiaries to: (1) quantify the prevalence of multimorbidity at COPD onset and one-year later; (2) quantify the rates [per 100 person-years (PY)] of newly diagnosed multimorbidity during in the year prior to and in the year following COPD onset; and (3) compare multimorbidity prevalence in beneficiaries with and without COPD. Among 739,118 eligible beneficiaries with and without COPD, the average number of multimorbidity was 10.0 (SD = 4.7) and 1.0 (SD = 3.3), respectively. The most prevalent multimorbidity at COPD onset and at one-year after, respectively, were hypertension (70.8% and 80.2%), hyperlipidemia (52.2% and 64.8%), anemia (42.1% and 52.0%), arthritis (39.8% and 47.7%), and congestive heart failure (CHF) (31.3% and 38.8%). Conditions with the highest newly diagnosed rates before and following COPD onset, respectively, included hypertension (39.8 and 32.3 per 100 PY), hyperlipidemia (22.8 and 27.6), anemia (17.8 and 20.3), CHF (16.2 and 13.2), and arthritis (12.9 and 13.2). COPD was significantly associated with increased odds of all measured conditions relative to non-COPD controls. This study updates existing literature with more current, generalizable findings of the substantial multimorbidity burden in medically complex older adults with COPD-necessary to inform patient-centered, multidimensional care.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2021.1968815 .

The Etiology of Pneumonia From Analysis of Lung Aspirate and Pleural Fluid Samples: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

BACKGROUND: An improved understanding of childhood pneumonia etiology is required to inform prevention and treatment strategies. Lung aspiration is the gold standard specimen for pneumonia diagnostics. We report findings from analyses of lung and pleural aspirates collected in the Pneumonia Etiology Research for Child Health (PERCH) study. METHODS: The PERCH study enrolled children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 countries in Africa and Asia. Percutaneous transthoracic lung aspiration (LA) and pleural fluid (PF) aspiration was performed on a sample of pneumonia cases with radiological consolidation and/or PF in 4 countries. Venous blood and nasopharyngeal/oropharyngeal swabs were collected from all cases. Multiplex quantitative polymerase chain reaction (PCR) and routine microbiologic culture were applied to clinical specimens. RESULTS: Of 44 LAs performed within 3 days of admission on 622 eligible cases, 13 (30%) had a pathogen identified by either culture (5/44) or by PCR (11/29). A pathogen was identified in 12/14 (86%) PF specimens tested by either culture (9/14) or PCR (9/11). Bacterial pathogens were identified more frequently than viruses. All but 1 of the cases with a virus identified were coinfected with bacterial pathogens. Streptococcus pneumoniae (9/44 [20%]) and Staphylococcus aureus (7/14 [50%]) were the predominant pathogens identified in LA and PF, respectively. CONCLUSIONS: Bacterial pathogens predominated in this selected subgroup of PERCH participants drawn from those with radiological consolidation or PF, with S. pneumoniae and S. aureus the leading pathogens identified.

Changes in Opioid Utilization Following Tumor Necrosis Factor Inhibitor Initiation in Patients with Rheumatoid Arthritis.

INTRODUCTION: Pain control is one of the most important aspects of rheumatoid arthritis (RA) management from the patient's perspective. Newer generations of RA treatment including tumor necrosis factor inhibitor (TNFi) have the potential to alleviate pain and thus reduce opioid utilization. However, patterns of opioid utilization before and after TNFi initiation have not been well characterized. This study aims to examine multiple measures of change in opioid utilization after the initiation of TNFi. METHODS: Patients aged ≥ 18 years with RA and 24 months continuous enrollment between January 2007 and December 2015 who newly initiated a TNFi in IQVIA™ Health Plan Claims Data were included in our study. Opioid utilization at baseline and during follow-up were identified and compared. RESULTS: Of 2330 patients with RA that were included in the study, 38.8% of patients used opioids in both baseline and follow-up periods. From pre-index to post-index, the proportion of patients receiving any opioid decreased from 54.0 to 51.0%. In addition, the proportion of those who received ≥ 50 mg median daily MED decreased from 12.6 to 10.6% during pre-post periods. CONCLUSIONS: This real-world study of commercially insured patients with RA suggests that opioid use among these patients is prevalent. There was a small decrease in overall opioid utilization after TNFi initiation.