Utilization and patient characteristics for the trastuzumab reference and biosimilars, and other human epidermal growth factor receptor 2 inhibitors in the United States.

BACKGROUND: Trastuzumab is an antihuman epidermal growth factor receptor 2 monoclonal antibody used to treat breast and other cancers. Trastuzumab biosimilars were approved in the United States beginning in 2017. Utilization information on these biosimilars is limited. OBJECTIVE: To examine utilization patterns and characteristics of patients treated with trastuzumab (biosimilars and reference) and other human epidermal growth factor receptor 2 products. METHODS: We evaluated health care claims data from the Biologics and Biosimilars Collective Intelligence Consortium distributed research network, representing a large, geographically diverse US population of commercially insured individuals. We queried 4 distributed research network health plan partners to capture product usage data and patient information from October 1, 2016, to October 31, 2022. Patients were required to be continuously enrolled in their health plan for at least 365 days before their first observed trastuzumab utilization date in this study period. Data were aggregated across data partners. RESULTS: More than 16 million eligible health plan members representing more than 31 million person-years of data were evaluated. We identified 5,984 incident treatment episodes; 3,878 (64.8%) episodes were with the reference trastuzumab. The mean ages were consistent across trastuzumab products (60.2 to 65.1 years) and at least 80% of the episodes were among female patients. The mean comorbidity index score was 1.2 (SD = 1.9) among users of the reference vs the biosimilars (range 1.2-2.5). Other clinical characteristics (eg, diabetes, hypertension) were comparable across products. The proportion of total incident episodes of the reference trastuzumab decreased substantially over time (96% in 2016 vs 28% in 2021) as utilization of the biosimilars increased (eg, use of trastuzumab-anns increased from 2% [2019] to 36% [2021]). Similar utilization trends were seen among patients with and without metastatic breast cancer. CONCLUSIONS: Trastuzumab biosimilars utilization has grown since their introduction to the US market. Exploration of these biosimilars' comparative effectiveness and safety to their reference product is warranted.

Trends in the Completeness and Validity of Sources of Death Data Against the National Death Index From 2010 to 2018.

PURPOSE: We investigated time trends in validation performance characteristics for six sources of death data available within the Healthcare Integrated Research Database (HIRD) over 8 years. METHODS: We conducted a secondary analysis of a cohort of advanced cancer patients with linked National Death Index (NDI) data identified in the HIRD between 2010 and 2018. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for six sources of death status data and an algorithm combining data from available sources using NDI data as the reference standard. Measures were calculated for each year of the study including all members in the cohort for at least 1 day in that year. RESULTS: We identified 27 396 deaths from any source among 40 692 cohort members. Between 2010 and 2018, the sensitivity of the Death Master File (DMF) decreased from 0.77 (95% CI = 0.76, 0.79) to 0.12 (95% CI = 0.11, 0.14). In contrast, the sensitivity of online obituary data increased from 0.43 (95% CI = 0.41, 0.45) in 2012 to 0.71 (95% CI = 0.68, 0.73) in 2018. The sensitivity of the composite algorithm remained above 0.83 throughout the study period. PPV was observed to be high from 2010 to 2016 and decrease thereafter for all sources. Specificity and NPV remained at high levels throughout the study. CONCLUSIONS: We observed that the sensitivity of mortality data sources compared with the NDI could change substantially between 2010 and 2018. Other validation characteristics were less variable. Combining multiple sources of mortality data may be necessary to achieve adequate performance particularly for multiyear studies.

Smaller Differences in the Comparative Effectiveness of Biologics in Reducing Asthma-Related Hospitalizations Compared With Overall Exacerbations.

BACKGROUND: Evidence on the comparative effectiveness of respiratory biologics remains sparse. OBJECTIVE: We sought to evaluate the comparative effectiveness of omalizumab, mepolizumab, benralizumab, and dupilumab in a matched retrospective cohort of patients with asthma. METHODS: We identified patients with asthma aged ≥18 years who were incident users of these biologics between November 1, 2018, and June 30, 2023, in administrative claims data from the Food and Drug Administration's Sentinel System and Merative MarketScan Commercial Database. We compared asthma-related exacerbations and hospitalizations in the 12 months since biologic prescription in pairwise comparisons of propensity score-matched cohorts. Covariates used in matching included age, sex, allergic comorbidities, baseline asthma medications use, and the Charlson Comorbidity Index. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using negative binomial regression models. RESULTS: A total of 893 patients on mepolizumab, 1300 on benralizumab, 1170 on omalizumab, and 1863 on dupilumab were identified. The average age was 55 years, and two-thirds of the participants were female. At baseline, over 80% of these individuals had an active prescription for an inhaled corticosteroid. Almost half of patients on dupilumab had concomitant nasal polyposis compared with 6% to 13% of patients on the other biologics. Covariates were balanced after matching. In matched analyses, dupilumab was associated with the lowest incidence of exacerbations over the follow-up period (vs dupilumab): mepolizumab (IRR: 1.36; 95% CI: 1.12, 1.64), omalizumab (IRR: 1.33; 95% CI: 1.13, 1.58), benralizumab (IRR: 1.19; 95% CI: 1.00, 1.41). For exacerbations leading to hospitalizations, benralizumab and mepolizumab were associated with the lowest incidence of hospitalizations, and the greatest difference was between mepolizumab versus dupilumab (IRR: 0.76; 95% CI: 0.56, 1.03). CONCLUSIONS: Dupilumab was associated with the lowest incidence of overall exacerbations, and mepolizumab with the lowest incidence of asthma hospitalizations in this administrative claims-based cohort of individuals with asthma. Despite matching propensity scores, residual confounding, such as baseline eosinophil count, may explain some of these findings.

Identification of cancer chemotherapy regimens and patient cohorts in administrative claims: challenges, opportunities, and a proposed algorithm.

BACKGROUND: Real-world evidence is a valuable source of information in healthcare. This study describes the challenges and successes during algorithm development to identify cancer cohorts and multi-agent chemotherapy regimens from claims data to perform a comparative effectiveness analysis of granulocyte colony stimulating factor (G-CSF) use. METHODS: Using the Biologics and Biosimilars Collective Intelligence Consortium's Distributed Research Network, we iteratively developed and tested a de novo algorithm to accurately identify patients by cancer diagnosis, then extract chemotherapy and G-CSF administrations for a retrospective study of prophylactic G-CSF. RESULTS: After identifying patients with cancer and subsequent chemotherapy exposures, we observed only 12% of patients with cancer received chemotherapy, which is fewer than expected based on prior analyses. Therefore, we reversed the initial inclusion criteria to identify chemotherapy receipt, then prior cancer diagnosis, which increased the number of patients from 2,814 to 3,645, or 68% of patients receiving chemotherapy had diagnoses of interest. Additionally, we excluded patients with cancer diagnoses that differed from those of interest in the 183 days before the index date of G-CSF receipt, including early-stage cancers without G-CSF or chemotherapy exposure. By removing this criterion, we retained 77 patients who were previously excluded. Finally, we incorporated a 5-day window to identify all chemotherapy drugs administered (excluding oral prednisone and methotrexate, as these medications may be used for other non-malignant conditions) as patients may fill oral prescriptions days to weeks prior to infusion. This increased the number of patients with chemotherapy exposures of interest to 6,010. The final cohort of included patients, based on G-CSF exposure, increased from 420 from the initial algorithm to 886 using the final algorithm. CONCLUSIONS: Medications used for multiple indications, sensitivity and specificity of administrative codes, and relative timing of medication exposure must all be evaluated to identify patient cohorts receiving chemotherapy from claims data.

Incidence of safety events after immune checkpoint inhibitor initiation for advanced-stage non-small-cell lung cancer: a real-world study.

Aim: To describe the incidence of safety events after immune checkpoint inhibitor (ICI) initiation for advanced-stage non-small-cell lung cancer. Methods: Retrospective cohort study using the HealthCore Integrated Research Database in the USA to examine the incidence of prespecified safety events of interest after ICI initiation (n = 5278). Results: The most common safety events after ICI initiation included malaise/fatigue (incidence rate [IR]: 70.7 per 100 person-years; 95% CI: 66.5-75.1) and nausea/vomiting (IR: 32.4; 30.0-34.8). Other potential immune-mediated events, including colitis (IR: 7.11; 6.26-8.04) and pneumonitis (IR: 5.47; 4.76-6.25), were less frequent but higher than after any systemic anti-cancer therapy. No safety event rate substantially increased 6 months after ICI initiation. Conclusion: This large real-world study reports the incidence of safety events with ICI regimens for advanced-stage non-small-cell lung cancer.

Researchers wanted to investigate side effects identified with advanced lung cancer during treatment, particularly immunotherapy. To investigate these side effects, researchers examined health insurance claims records from patients who were diagnosed with advanced lung cancer between January 2010 and July 2019, and who received treatment at various clinics across the USA. Researchers identified records for 44,045 patients treated for advanced lung cancer, with 5278 being treated with immunotherapy. After patients started immunotherapy, the most commonly reported side effects were tiredness and nausea/vomiting. Other side effects possibly related to immunotherapy were inflammation of the large intestine and lung inflammation ­ these events were not reported very often and did not increase in frequency 6 months after start of treatment. This large real-world study provides estimates for the frequency of side effects for those treated for advanced lung cancer, and finds that there were no large increases in the occurrence of any particular side effect in the 6 months after patients started immunotherapy for advanced lung cancer.

Health care resource utilization and costs associated with advanced or metastatic nonsmall cell lung cancer in the United States.

BACKGROUND: The treatment landscape for advanced nonsmall cell lung cancer (NSCLC) has evolved from 2015 onward, since the introduction of immune checkpoint inhibitors (ICIs). Considering this shift, there have been limited prior analyses that assess the economic burden of NSCLC within the current treatment landscape. OBJECTIVE: To present an analysis of health care resource utilization (HCRU) and costs associated with the treatment of patients with advanced or metastatic NSCLC in the United States between 2010 and 2019. METHODS: Patients with locally advanced or metastatic NSCLC who initiated first-line (1L) systemic treatment between January 1, 2010, and June 30, 2019, were included from the HealthCore Integrated Research Database using a previously developed claims-based predictive model algorithm. Mean total HCRU and costs and mean per-person-per-year (PPPY) HCRU and costs were estimated for 2 follow-up periods: the time during the entire follow-up period and the time during the 1L treatment period. Distribution of treatment classes (defined as chemotherapy, ICIs, targeted therapies, and others) were also analyzed by index year. RESULTS: 27,257 patients met the eligibility criteria and were included in the analysis. The mean duration of follow-up for all patients was 16.6 months (median 10.6 months), and the median time to discontinuation of 1L treatment was 2.8 months. The number of outpatient visits accounted for the majority of HCRU across the entire study follow-up (mean 97.7 in total and 147.1 PPPY) and for the 1L treatment period (mean 46.3 in total and 167.5 PPPY). The total mean cost across the entire study follow-up was $158,908 ($250,942 PPPY). For the 1L treatment period, the total mean cost was $72,760 ($271,590 PPPY). Total mean outpatient costs for systemic anticancer treatment were $61,797 for the entire study follow-up ($85,609 PPPY) and $27,138 during the 1L treatment period ($92,412 PPPY). Total costs increased over the study duration, which were mainly due to increasing outpatient costs for systemic therapy. In both follow-up periods, inpatient costs, other outpatient costs (nonsystemic therapy-related costs), and pharmacy costs remained relatively stable but still accounted for more than 60% of the total costs. Analysis of treatment classes over time showed that chemotherapy was the most frequently used treatment, regardless of line of therapy. A trend was observed for increased ICI use from 2015 onward. CONCLUSIONS: Despite the improvement in treatment options, a high economic burden associated with the treatment of NSCLC still exists. The total costs have been increasing, mainly driven by outpatient costs for systemic therapy, which might reflect the greater use of ICIs for advanced NSCLC. Costs for inpatient services, other outpatient services, and pharmacy services remained stable but still accounted for the majority of the economic burden. Further studies are required to assess the impact of innovative treatments on the disease management costs of advanced NSCLC. DISCLOSURES: This study was funded by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945) as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany, and Pfizer. Zhang, Liu, and Yang are employees of EMD Serono. Beachler, Dinh, and Jamal-Allial are employees of HealthCore Inc., which received funding from the healthcare business of Merck KGaA, Darmstadt, Germany, and Pfizer for the implementation of this study. Masters and Kolitsopoulos are employees of Pfizer. Lamy was an employee of the healthcare business of Merck KGaA, Darmstadt, Germany, at the time this study was conducted.

Characteristics of new adult users of mepolizumab with asthma in the USA.

BACKGROUND: In the USA, over 25 million people have asthma; 5%-10% of cases are severe. Mepolizumab (Nucala) is an interleukin-5 antagonist monoclonal antibody; it was approved by the FDA in 2015 as add-on maintenance treatment of severe asthma for patients aged ≥12 years with an eosinophilic phenotype. OBJECTIVES: (1) Describe baseline demographic and clinical characteristics of new US adult mepolizumab users 2015-2019, (2) describe asthma medication use in the 12 months preceding initiation of and concomitant with mepolizumab and (3) assess mepolizumab adherence, persistence and discontinuation patterns in 12 months postinitiation. METHODS: We conducted a new-user observational cohort study using data from Aetna, a CVS Health Company, HealthCore (Anthem), Harvard Pilgrim Healthcare, and IBM MarketScan Research Databases. Curated administrative claims data in the FDA Sentinel System common data model format and publicly available Sentinel analytical tools were used to query the databases. We included adults who initiated mepolizumab in 2015-2019 with an asthma diagnosis in the preceding 12 months and no evidence of cystic fibrosis. We examined age, sex, comorbid conditions, asthma medication use and severe asthma exacerbations. RESULTS: We identified 3496 adults (mean age 54.2 years, SD 12.5 years) who initiated mepolizumab. In the 12 months before mepolizumab initiation, 22% had received inhaled corticosteroids, 46% had inhaled corticosteroid/long-acting beta agonists, 72.6% had leukotriene antagonists, 38% had long-acting muscarinic antagonist, 18% had omalizumab,<1% had reslizumab, dupilumab or benralizumab. In the previous 12 months, 70% had a diagnosis of allergic rhinitis, 32% had chronic obstructive pulmonary disease, 17% eosinophilia and 3% eosinophilic granulomatosis with polyangiitis. Further, 56% had an asthma-related ambulatory visit, 73%≥1 course of oral corticosteroids lasting 3-27 days, 10% an asthma-related emergency department visit and 22% an asthma-related hospitalisation. In the 12 months following initiation, the mean proportion of days covered was 70%, and reductions in the average mean dispensings of rescue oral corticosteriods (35%) and omalizumab (61%) were observed. CONCLUSIONS: Adults with asthma treated with mepolizumab had varying levels of healthcare utilisation and we observed evidence of mepolizumab use in patients without severe asthma.

Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study.

BACKGROUND: There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. METHODS: We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. RESULTS: There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1-8.4). CONCLUSIONS: This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

A real-world study on characteristics, treatments and outcomes in US patients with advanced stage ovarian cancer.

BACKGROUND: Detailed epidemiologic descriptions of large populations of advanced stage ovarian cancer patients have been lacking to date. This study aimed to describe the patient characteristics, treatment patterns, survival, and incidence rates of health outcomes of interest (HOI) in a large cohort of advanced stage ovarian cancer patients in the United States (US). METHODS: This cohort study identified incident advanced stage (III/IV) ovarian cancer patients in the US diagnosed from 2010 to 2018 in the HealthCore Integrated Research Database (HIRD) using a validated predictive model algorithm. Descriptive characteristics were presented overall and by treatment line. The incidence rates and 95% confidence intervals for pre-specified HOIs were evaluated after advanced stage diagnosis. Overall survival, time to treatment discontinuation or death (TTD), and time to next treatment or death (TTNT) were defined using treatment information in claims and linkage with the National Death Index. RESULTS: We identified 12,659 patients with incident advanced stage ovarian cancer during the study period. Most patients undergoing treatment received platinum agents (75%) and/or taxanes (70%). The most common HOIs (> 24 per 100 person-years) included abdominal pain, nausea and vomiting, anemia, and serious infections. The median overall survival from diagnosis was 4.5 years, while approximately half of the treated cohort had a first-line time to treatment discontinuation or death (TTD) within the first 4 months, and a time to next treatment or death (TTNT) from first to second-line of about 6 months. CONCLUSIONS: This study describes commercially insured US patients with advanced stage ovarian cancer from 2010 to 2018, and observed diverse treatment patterns, incidence of numerous HOIs, and limited survival in this population.

The longitudinal association of vitamin D serum concentrations & adiposity phenotype.

Several cross-sectional studies have reported on the association between serum 25-hydroxy vitamin D concentrations (25(OH)D) and body mass index (BMI). We examined the longitudinal effect of BMI on serum 25(OH)D concentrations among 866 Puerto Rican adults living in the Greater Boston area: 246 men and 620 women, aged 45-75 years at baseline and 2 year. Our analyses showed negative correlations at two time points between BMI and serum 25(OH)D concentrations. The multivariate analysis showed that when predicting the change of serum 25(OH)D concentrations, baseline-BMI had significant inverse association (P<0.04) controlling for age, sex, and baseline-BMI. This association remained significant after adjusting for vitamin D supplement use, smoking, miles walked/day and alcohol intake (P<0.01). In conclusion, the major findings of the present study are obesity (1) was inversely associated with 25(OH)D at baseline; (2) with the change in serum 25(OH)D at 2-year in this population of older Puerto Rican adults living in the Boston area. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.