Cost-Effectiveness Comparison between Ibrutinib, Chemotherapy, and Chemoimmunotherapy in Front-Line Treatment of Chronic Lymphocytic Leukemia (CLL)
Authors: Nabhan Chadi , Nero Damion , Lee Choo Hyung , Kish Jonathan K. , Mato Anthony R. 
Published: October 2019

Abstract
INTRODUCTION: CLL pts requiring first-line therapy are usually treated with either ibrutinib, chemotherapy alone including monoclonal antibodies (CT), or chemoimmunotherapy (CIT). In the absence of prospective efficacy data comparing CIT with ibrutinib, treatment selection depends on risk stratification, comorbidities, age, goals of therapy, pt preference, and physician familiarity with regimens. When all factors are equal, costs and economics might influence treatment choice especially in a value-based care environment. We performed a cost-comparative analysis between ibrutinib, CT, and CIT-treated CLL pts in the first line aiming to provide additional guidance for clinicians when deciding on initial therapy.
PATIENTS and METHODS: This is a retrospective, observational study of CLL pts treated in the first line with ibrutinib, CT, or CIT. Primary end-point was to compare healthcare resource utilization (HRU) between pts in each cohort. Secondary objective was to quantify the incidence of cardiovascular (CV) adverse events between pts who did not have any CV disease prior to treatment initiation. Pts were extracted from Symphony Health's Integrated Dataverse (IDV) between 1/1/2014-12/31/2017. The database is representative of the U.S. population across age, sex, geography, and insurance type. Pts were ≥18 years at diagnosis and initiated therapy after 1/1/2014 and before 11/30/2017 to allow for at least 3 months of follow up. Pts were required to have no CV events during the 12-month period before study entry. CV events included hypertension (HTN), myocardial infarction (MI), atrial fibrillation (Afib), peripheral vascular disease (PVD) and coronary artery disease (CAD). HRU was evaluated using admission codes for hospitalization, emergency room (ER), office visits, and other outpatient visits. Direct medical costs were calculated based on standardized costs and were estimated in US dollars as per patient per month. Comparisons of HRU and costs and the proportion of pts with a CV event were performed using the chi square or Fisher exact test for proportions and the t-test or Wilcoxon rank sum test for continuous data. Fisher exact test and the Wilcoxon rank-sum test were used in cases where the data did not have a normal distribution. The Kruskal-Wallis test was used in cases where multiple groups were being compared.
RESULTS: The final cohorts included 4,368 pts receiving ibrutinib, 1,464 receiving CT, and 2,176 treated with CIT (1,523 BR, 634 FCR, and 19 chlorambucil combinations). Mean age at diagnosis and treatment initiation for ibrutinib was 66 and 68 respectively, which was younger than CT (68 and 70 respectively), but older than CIT (62 and 63 respectively). Other characteristics were similar in the three cohorts. Median time from diagnosis to treatment was longer in ibrutinib-treated pts versus CT and CIT (17.4 vs. 10.9 vs. 7.8 months; p<0.0001). CT and CIT pts had significantly higher costs and HRU compared with ibrutinib pts for office and outpatient visits (p<0.0001). ER visits were significantly higher for both CT and CIT pts (p<0.05) while ER costs were slightly higher for ibrutinib pts but not statistically significant. Inpt visits, costs and length of stay were significantly different in CIT pts compared to ibrutinib, but not in CT pts. More pts on ibrutinib developed AFib compared with CIT-treated pts (4.42% vs. 2.67%; p=0.0005). More CIT-treated pts developed HTN compared with the ibrutinib cohort, though the difference was not significant (11.1% vs. 9.8%; p=0.0871). A total of 567 pts (13%) taking ibrutinib went on to have a CV event while 3,801 patients continued therapy without an event. We found significantly higher HRU for ibrutinib pts with and without CV events for outpatient visits (3.86 vs 3.46, p-value <0.0001), office visits (1.04 vs 0.91, p <0.0048), ER visits (p=0.006), ER costs (p<0.0001), and length of inpt stay (3.18 vs. 2.56; p<0.0001). Lastly, we found a significant difference between Medicare/Medicaid and commercial payers in the number of outpt visits (3.581 vs. 3.378 p=0.0002) and the cost of oupt visits (1,507.36 vs 1,126.84, p<0.0001) (Table).
CONCLUSIONS: When used as front-line, ibrutinib has lower HRU and ER visits than CT/CIT pts. More ibrutinib-treated patients developed AFib than CT/CIT pts. CV events in ibrutinib-treated pts were observed in 13% of cases and had substantial impact on cost of care.

Disclosures
Nabhan: Cardinal Health: Employment, Equity Ownership. Nero:Cardinal Health: Employment. Lee:Cardinal Health: Employment. Kish:Cardinal Health: Employment. Mato:Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; AstraZeneca: Consultancy; Celgene: Consultancy; Regeneron: Research Funding; AbbVie: Consultancy, Research Funding; Medscape: Honoraria; Acerta: Research Funding; Portola: Research Funding; TG Therapeutics: Consultancy, Research Funding; Prime Oncology: Honoraria; Johnson & Johnson: Consultancy.