Cost-effectiveness of treatment of darvadstrocel in combination with standard of care compared to placebo added to standard of care for refractory complex perianal fistulas in patients with Crohn's disease in Norway.

Abstract

Background: Complex perianal fistula in Crohn’s disease (cPFCD) is considered a most challenging manifestation of CD that associated with severe impairment on patient’s quality of life and substantial morbidity. There remains an unmet need of treatment for maintaining long-term fistula closure. Recently published phase III ADMIRE-CD trial results showed the stem cell therapy darvadstrocel combined with standard care had promising efficacy on fistula remission, which may significantly improve patients’ quality of life and reduce societal burden, but evidence on cost-effectiveness is limited. Research objective: to investigate the cost-effectiveness of the second-line treatment of darvadstrocel combined with standard care compared to placebo added to standard care for refractory complex perianal fistulas in patients with Crohn's disease in Norway. Methods: A decision analytic model combining decision tree and Markov processes was developed to estimate the cost-effectiveness of darvadstrocel in combine with standard care strategy compared with standard care alone therapy in Norway. Expected costs and effects were calculated from a healthcare perspective and a societal perspective over a 5-year time horizon. The health outcome measure was the incremental cost per quality-adjusted life year (QALY). Sensitivity and scenario analyses were performed to evaluate the uncertainty of the model. Costs and effects were discounted at 4%. Results: From the healthcare perspective, darvadstrocel strategy was associated with a total cost increase of NOK 744095.57 and a QALY gain of 0.416 compared to placebo strategy, corresponding with an ICER of NOK 1788691.27 per QALY gained. After taking into account productivity costs, darvadstrocel strategy resulted in a cost increase of NOK 609660.79 and a QALY gain of 0.416 compared to placebo strategy. This generated a lower ICER of NOK 1466764.80 per QALY gained. Differences in costs significantly drove the incremental cost-effectiveness than the effectiveness and the cost of darvadstrocel was the major contributor of the costs difference. The PSA indicated that treatment of darvadstrocel added to standard of care can be considered cost-effective if society is willing to pay more than NOK 1570,000 per person if productivity costs are included, and NOK 1700,000 per person when only healthcare costs are considered. One-way sensitivity analysis found that the ICER was more influenced by the utility of remission health state, darvadstrocel unit cost, the utility of active disease health state and transition probabilities from active disease health state to other health states in placebo strategy group. Scenario analysis showed ICERs reduced dramatically with a longer time horizon. Severity is measured by absolute shortfall (AS), which is 9.36 QALYs. Conclusion: In the base case analysis, the probability that darvadstrocel added to standard of care is cost-effective is only 28% with a willingness-to-pay of NOK 1000,000 from a societal perspective and 26% from a healthcare perspective. Further research is needed to conduct the budget impact in order to evaluate the eligibility of darvadstrocel therapy in Norway.