Grade 3/4 Adverse Event Costs of Immuno-oncology Combination Therapies for Previously Untreated Advanced Renal Cell Carcinoma.

BACKGROUND: Despite 4 approved combination regimens in the first-line setting for advanced renal cell carcinoma (aRCC), adverse event (AE) costs data are lacking. MATERIALS AND METHODS: A descriptive analysis on 2 AE cost comparisons was conducted using patient-level data for the nivolumab-based therapies and published data for the pembrolizumab-based therapies. First, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib using data from the CheckMate 214 (median follow-up [mFU]: 13.1 months), CheckMate 9ER (mFU: 12.8 months), and KEYNOTE-426 (mFU: 12.8 months) trials, respectively. Second, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib using data from the CheckMate 214 (mFU: 26.7 months), CheckMate 9ER (mFU: 23.5 months), and KEYNOTE-581 (mFU: 26.6 months) trials, respectively. Per-patient costs for all-cause and treatment-related grade 3/4 AEs with corresponding any-grade AE rates ≥ 20% were calculated based on the Healthcare Cost and Utilization Project database and inflated to 2020 US dollars. RESULTS: Per-patient all-cause grade 3/4 AE costs for nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib were $2703 vs. $4508 vs. $5772, and treatment-related grade 3/4 AE costs were $741 vs. $2722 vs. $4440 over ~12.8 months of FU. For nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib, per-patient all-cause grade 3/4 AE costs were $3120 vs. $5800 vs. $9285, while treatment-related grade 3/4 AE costs were $863 vs. $3162 vs. $5030 over ~26.6 months of FU. CONCLUSION: Patients with aRCC treated with first-line nivolumab-based therapies had lower grade 3/4 all-cause and treatment-related AE costs than pembrolizumab-based therapies, suggesting a more favorable cost-benefit profile.

Temporal trends of adverse events and costs of nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma.

Aims: To assess grade 3/4 adverse events (AEs) and costs of first-line nivolumab plus ipilimumab versus sunitinib in advanced or metastatic renal cell carcinoma. Methods: Individual patient data from the all treated population in the CheckMate 214 trial (nivolumab plus ipilimumab, n = 547; sunitinib, n = 535) were used to calculate the number of AEs. AE unit costs were obtained from US 2017 Healthcare Cost and Utilization Project and inflated to 2020 values. Results: The proportion of patients experiencing grade 3/4 AEs decreased over time. Patients who received nivolumab plus ipilimumab had lower average per-patient all-cause grade 3/4 AE costs versus sunitinib (12-month: US$15,170 vs US$20,342; 42-month: US$19,096 vs US$27,473). Conclusion: Treatment with nivolumab plus ipilimumab was associated with lower grade 3/4 AE costs than sunitinib.

Immunotherapy combinations are now accepted as safe and effective first-line treatment options for advanced or metastatic renal cell carcinoma. This study used patient data from the CheckMate 214 clinical trial to evaluate the temporal trends and costs related to grade 3/4 adverse events (AEs) among patients treated with nivolumab plus ipilimumab versus sunitinib. We found that the proportion of patients experiencing grade 3/4 AEs decreased over time and that patients treated with nivolumab plus ipilimumab had lower AE costs compared with those treated with sunitinib (at 42 months: US$19,096 vs US$27,473 per patient). As such, nivolumab plus ipilimumab may represent a treatment option that may reduce both the clinical and economic burden among patients with advanced or metastatic renal cell carcinoma.

Burden of Herpes Zoster Among Patients with Psoriatic Arthritis in the United States.

Purpose: Patients with psoriasis (PsO) and psoriatic arthritis (PsA) are at increased risk of herpes zoster (HZ), but healthcare resource use (HRU) and costs relating to HZ in adults with PsA are unknown. We aimed to estimate the incidence of HZ among adults with PsA vs without psoriatic disease and the additional HRU and costs among patients with PsA with vs without HZ. Patients and Methods: This retrospective, longitudinal, cohort study estimated HZ incidence in PsA+ vs PsO-/PsA- cohorts and HRU and medical/pharmacy costs among PsA+/HZ+ vs PsA+/HZ- cohorts comprised of adults from Optum's de-identified Clinformatics Data Mart Database during 2015-2020. For the HRU/cost analyses, index was the date of first HZ diagnosis (PsA+/HZ+ cohort) or was randomly assigned (PsA+/HZ- cohort). Generalized linear models were used for adjusted comparisons between cohorts. Results: HZ incidence was higher in the PsA+ (n = 57,126) vs PsO-/PsA- (n = 23,837,237) cohort (14.85 vs 7.67 per 1000 person-years; adjusted incidence rate ratio [aIRR]: 1.23; 95% confidence interval [CI]: 1.16-1.30). Numbers of outpatient visits, emergency department visits, and inpatient admissions were significantly higher in the PsA+/HZ+ (n = 1045) vs PsA+/HZ- (n = 36,091) cohorts during the first month after HZ diagnosis (outpatient: aIRR: 1.74; 95% CI: 1.63-1.86; emergency department: 3.14; 95% CI: 2.46-4.02; inpatient: aIRR: 2.61; 95% CI: 1.89-3.61). Mean all-cause per-patient costs were significantly higher in the PsA+/HZ+ vs PsA+/HZ- cohorts during the first month after index ($6493 vs $4521; adjusted cost difference: $2012; 95% CI: $1204-$3007). HRU and costs were numerically higher in the PsA+/HZ+ cohort during the first 3 and 12 months. Conclusion: These findings, which provide evidence on the increased incidence and HRU and economic burden associated with HZ among adults with PsA, could be used to inform clinical practice and decision-making.

Why was the study done? Psoriatic arthritis affects the joints of around 20% of patients with the skin condition, psoriasis.Patients with psoriatic arthritis are at increased risk of shingles, which can cause a painful skin rash and complications.This study aimed to provide information on how many patients with psoriatic arthritis get shingles and the healthcare use and costs of caring for patients with psoriatic arthritis and shingles. What did the researchers do and find? Using data from a large US health plan database, we estimated that for every 1000 patients with psoriatic arthritis observed for 1 year, 15 will develop shingles.Patients with psoriatic arthritis were 23% more likely to develop shingles than people without psoriatic disease.Patients with psoriatic arthritis and shingles had 2­3 times as many healthcare visits in the month after a shingles diagnosis as patients with psoriatic arthritis but no shingles.This resulted in an average additional cost of approximately $2000 per patient. What do these results mean? Psoriatic arthritis increases the risk of shingles.The costs associated with shingles in patients with psoriatic arthritis are substantial.Measures to prevent shingles in this population could be beneficial.

Treatment Patterns and Adverse Event-Related Hospitalization Among Patients with Epidermal Growth Factor Receptor (EGFR)-Mutated Metastatic Non-small Cell Lung Cancer After Treatment with EGFR Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy Regimens.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKIs) are established first-line treatments among patients with metastatic non-small cell lung cancer harboring EGFR-sensitizing mutations. Upon EGFR TKI resistance, there are scant data supporting a standard of care in subsequent lines of therapy. OBJECTIVE: We aimed to characterize real-world treatment patterns and adverse events associated with hospitalization in later lines of therapy. METHODS: This retrospective analysis of administrative claims included adults with metastatic non-small cell lung cancer who initiated a next line of therapy (index line of therapy) following EGFR TKI and platinum-based chemotherapy discontinuation on/after 1 November, 2015. Treatment regimens and adverse event rates during the index line of therapy were described. RESULTS: Among 195 eligible patients (median age: 59 years; female: 60%), the five most common index line of therapy regimens were immune checkpoint inhibitor monotherapy (29%), EGFR TKI monotherapy (21%), platinum-based chemotherapy (19%), non-platinum-chemotherapy (13%), and EGFR TKI combinations (9%). The overall median (95% confidence interval) time to discontinuation of the index line of therapy was 2.8 (2.1-3.2) months. Common adverse events associated with hospitalizations included infection/sepsis, pneumonia/pneumonitis, and anemia (2.9, 2.8, and 2.0 per 100 person-months, respectively). CONCLUSIONS: Among EGFR TKI-resistant patients who discontinued platinum-based chemotherapy, the duration of the next line of therapy was short, treatment was highly variable, and re-treatment with EGFR TKIs and platinum-based regimens was common, suggesting a lack of standard of care in later lines. Adverse event rates associated with hospitalization were high, especially among platinum-treated patients. These results underscore the unmet need for new therapies in a later line of treatment to reduce the clinical burden among patients in this population.

Burden of Herpes Zoster Among Patients with Psoriasis in the United States.

INTRODUCTION: Patients with psoriasis (PsO) are at increased risk of herpes zoster (HZ), but recent data on the incidence of HZ among patients with PsO and the impact of HZ on healthcare resource use (HRU) and costs for patients with PsO have not been described. METHODS: This retrospective, longitudinal, cohort study estimated HZ incidence in cohorts of adults with vs without PsO (PsO + vs PsO-) and HRU and costs among those with PsO, with vs without HZ (PsO + /HZ + vs PsO + /HZ-) using Optum's de-identified Clinformatics Data Mart Database during 2015-2020. Patients with psoriatic arthritis were excluded from all four cohorts. Comparisons between cohorts used generalized linear models to adjust outcomes based on various baseline characteristics. RESULTS: The incidence rate of HZ was significantly higher in the PsO + (n = 144,115) vs PsO- (n = 23,837,237) cohorts at 11.35 vs 7.67 per 1000 patient-years; adjusted incidence rate ratio (aIRR): 1.21, 95% confidence interval (CI): 1.16-1.25. HRU (outpatient, emergency department, and inpatient) was significantly higher in the PsO + /HZ + (n = 1859) vs PsO + /HZ- (n = 78,664) cohorts during 1 month and 3 months after HZ diagnosis (e.g., outpatient visits during month: 2.83 vs 1.30 per patient; aIRR: 1.96; 95% CI 1.86-2.06). Mean all-cause costs were also significantly higher in the PsO + /HZ + vs PsO + /HZ- cohort during both month ($5020 vs $2715 per patient; adjusted cost difference: $1390; 95% CI $842-$1964) and 3 months ($12,305 vs $8256; adjusted cost difference: $1422; 95% CI $280-$2889) after HZ diagnosis. CONCLUSION: These findings show the increased incidence of HZ among patients with PsO and the clinical and economic burdens of HZ in this population. Considering the high prevalence of PsO, insights into the impact of HZ in these patients provide valuable evidence to inform clinical decision-making.

Psoriasis is an inflammatory condition that causes flaky, scaly skin. Herpes zoster (shingles) causes a painful rash, usually on the abdomen. However, recent data on the proportion of patients with psoriasis who develop herpes zoster is lacking. Furthermore, little is known about the healthcare resources that are used or the costs of care for patients with psoriasis who develop herpes zoster. We found that patients with psoriasis were 21% more likely to have herpes zoster than patients without psoriasis. Among patients with psoriasis, those who developed herpes zoster had twice as many doctor's visits, 3 times as many emergency department visits, and twice as many inpatient hospital stays during the month after a herpes zoster diagnosis as patients without herpes zoster. This resulted in an additional cost of $1390 per patient with psoriasis and herpes zoster compared with those with psoriasis but without herpes zoster. Overall, patients with psoriasis are at increased risk of developing herpes zoster and the healthcare resource use and associated cost of treating herpes zoster in patients with psoriasis is substantial.

Health care costs and resource utilization among commercially insured adult patients with hemophilia A managed with FVIII prophylaxis in the United States.

BACKGROUND: Standard of care for patients with severe hemophilia A (HA) is life-long prophylaxis with factor VIII (FVIII) concentrate or other hemostatic agents. Published literature highlights a wide range of treatment costs for patients with HA. OBJECTIVE: To estimate average annual health care costs and resource utilization for a cross-section of adult patients managed with FVIII concentrate prophylaxis using recent data from a large US commercial claims database. METHODS: Adult males with 1 or more claim with HA diagnosis, continuous commercial plan enrollment, and 4 or more FVIII prescription dispenses during 12 months were identified from IBM MarketScan Research Database from January 2013 to September 2019, excluding those with FVIII inhibitors, an HIV/AIDS diagnosis, or diagnosis and treatment for hepatitis B or C. Patients were classified as using FVIII prophylaxis if they met any of the following definitions: (1) 6 or more FVIII dispenses, (2) a gap of 60 days or less between dispenses, and (3) at least 273 days supply in the 12-month period. Additionally, subgroups of patients meeting each individual definition were examined, with some patients included in all 3 subgroups. RESULTS: The overall cohort included 411 patients who met 1 or more of the 3 definitions, with a mean age of 28.9 years. Subgroups of 401, 325, and 237 patients met the first, second, and third FVIII prophylaxis definitions, respectively. Per-patient mean (SD) annual all-cause health care costs were $654,571 ($380,762) in the overall cohort and ranged from $650,065 ($382,196) to $759,661 ($387,040) among subgroups. Cost of FVIII concentrate accounted for more than 96% of total costs in the overall cohort and in each subgroup. Cost of FVIII in the overall cohort varied according to type of concentrate, with the highest among patients who were treated with both standard and extended half-life (SHL and EHL) FVIII ($784,945), followed by EHL FVIII only ($708,928), SHL FVIII only ($647,800), and plasma-derived FVIII ($535,614). The most common treatment type was SHL FVIII only (45.7% of all patients). In the overall cohort, the majority had 1 or more outpatient visits (94.9%), while emergency department visits, hospital admissions, and home health visits occurred less frequently (27.0%, 7.1%, and 7.1%, respectively). CONCLUSIONS: Commercially insured patients with HA incur substantial all-cause annual health care costs, with FVIII concentrate accounting for a majority of costs. DISCLOSURES: This study was funded by BioMarin Pharmaceutical Inc, which was involved in the protocol development, analysis plan development, data interpretation, manuscript preparation, and publication decisions. All authors contributed to protocol development, analysis plan development, data interpretation, and manuscript development and maintained control over the final content. Thornburg has received professional fees from BioMarin Pharmaceutical, CSL Behring, Genentech, Novo Nordisk, Sanofi Genzyme, HEMA Biologics, and Spark Therapeutics and institutional research funding from BioMarin Pharmaceutical, Novo Nordisk, and Sanofi Genzyme. Adamski, Cook, and Sendhil are employees of Analysis Group, a consulting company that was contracted by BioMarin Pharmaceutical to conduct this study and develop the manuscript. Vembusubramanian is a former employee of Analysis Group. Hinds, Chen, and Sammon are employees and shareholders of BioMarin Pharmaceutical. Solari is a former employee of BioMarin Pharmaceutical. Garrison has received consulting fees from BioMarin Pharmaceutical and Analysis Group. Croteau has received professional fees from BioMarin Pharmaceutical, Bayer, CSL Behring, HEMA Biologics, and Pfizer and institutional research funding from Novo Nordisk and Spark Therapeutics.

Efficacy of avapritinib versus best available therapy in the treatment of advanced systemic mastocytosis.

Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER. Comparisons between outcomes of OS, duration of treatment (DOT), and maximum reduction in serum tryptase were conducted between the treatment cohorts, with adjustment for key covariates. The results indicated that the avapritinib cohort had significantly better survival (adjusted hazard ratio (HR) (95% confidence interval (CI)): 0.48 (0.29, 0.79); p = 0.004) and significantly longer DOT (HR: 0.36 (0.26, 0.51); p < 0.001) compared to the BAT cohort. Additionally, the mean difference in percentage maximum reduction in serum tryptase levels was 60.3% greater in the avapritinib cohort (95% CI: -72.8, -47.9; p < 0.001). With no randomized controlled trials comparing avapritinib to BAT, these data offer crucial insights into the improved efficacy of avapritinib for the treatment of AdvSM.