## Abstract

Abstract 4255

Background:

Ruxolitinib demonstrated significant clinical benefits for patients (pts) with myelofibrosis (MF) in two phase 3 COMFORT studies. Nevertheless, in countries where health technology assessments are conducted, cost-effectiveness is an important consideration. Economic evaluations play an increasingly important role in reimbursement decisions for new treatments. To help inform such decisions, an evaluation of the cost-effectiveness (CE) of adding ruxolitinib as a treatment for MF was conducted from a Canadian societal perspective.

Methods:

A Markov model was built to estimate the costs, health outcomes, and CE of ruxolitinib compared with investigator-selected best available therapy (BAT), which included conventional therapies or no treatment. Data were derived from pts enrolled in the COMFORT-II study and included high-risk or intermediate-2–risk pts according to the International Working Group for Myelofibrosis Research and Treatment risk categorization. For this analysis, response was defined as a ≥ 35% reduction in spleen volume (COMFORT-II primary endpoint) or absence of constitutional symptoms. Survival assumptions were derived from a historical comparison of patients in the phase 1/2 study (Verstovsek et al, Blood. 2012) that showed a benefit for those achieving a ≥ 50% reduction in spleen length (equivalent to 35% spleen volume reduction). The model simulated disease progression in a cohort of pts with MF through 4 different health states with a 12-week cycle and a lifetime time horizon: 1) responder; 2) nonresponder; 3) leukemic transformation (LT); and 4) death. In each time cycle, pts incurred cost and utility estimates associated with their health state. The model considered the resource and utility implications arising from treatments aimed at directly treating splenomegaly, namely splenic irradiation and splenectomy. The outcomes of the Markov model included costs over the time horizon (drug costs, costs linked to the management of adverse events, other medical costs, indirect costs), life years, quality-adjusted life years (QALYs), and time spent as a responder to treatment. Both a 1-way sensitivity analysis and a probabilistic sensitivity analysis were performed, using estimated ranges and probability distributions for each input parameter.

Results:

The results showed that ruxolitinib-treated pts with MF had a better clinical outcome but at an increased cost. The total average lifetime cost of treating a pt receiving ruxolitinib was $494,859 CAD, with drug costs of$205,484 and other medical costs of $217,527, the majority of which were resource costs. The total average lifetime cost of treating a pt receiving BAT was$421,755, of which $59,289 was drug costs. Indirect costs were higher for BAT pts, at$96,458, exceeding the figure of $71,848 for ruxolitinib pts (Table). The clinical results showed longer average overall survival for pts receiving ruxolitinib compared with pts receiving BAT (Verstovsek et al, Blood. 2012). The ruxolitinib-treated pts had 4.01 QALYs compared with 2.82 QALYs for those in the BAT arm. The overall incremental CE ratio (ICER) was$61,444 per QALY. The key model drivers were the resource cost for nonresponders and improved mortality in the intermediate-2–risk group. Adopting a $100,000 per QALY willingness-to-pay threshold showed that 100% of the simulations for ruxolitinib therapy would be cost-effective compared with BAT for the treatment of MF. The mean ICER from the simulations was$59,216 per QALY, which was similar to the deterministic average of $61,444. Conclusions: There has been a high, unmet need for an effective therapeutic option for pts with MF. The COMFORT-II study has shown that ruxolitinib is clinically effective and superior to BAT at reducing splenomegaly and disease-related symptoms and improving health-related quality of life. The present analysis suggests that compared with BAT, ruxolitinib is an economically acceptable treatment option. Continued long-term evaluation of survival and potential reduction in rates of LT will also impact the future CE of ruxolitinib. Table. Comparison of Total Lifetime Costs RuxolitinibBAT Total average lifetime cost$494,859 $421,755 Drug costs$205,484 $59,289 Other medical costs$217,527 $266,008 Indirect costs$71,848 $96,458 Total average patient outcomes QALY 4.01 2.82 ICER$61,444/QALY
RuxolitinibBAT
Total average lifetime cost $494,859$421,755
Drug costs $205,484$59,289
Other medical costs $217,527$266,008
Indirect costs $71,848$96,458
Total average patient outcomes
QALY 4.01 2.82
ICER \$61,444/QALY
Disclosures:

El Ouagari:Novartis Pharma: Employment. Knight:Novartis Pharmaceuticals Corporation: Consultancy; Novartis Pharmaceuticals Canada: Consultancy. Mendelson:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership.

## Author notes

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Asterisk with author names denotes non-ASH members.