Cost-Effectiveness of Third-Line Anti-TNF Therapy Compared to Natalizumab in Patients With Moderate-to-Severe Crohn's Disease With Two Prior Anti-TNF Failures

Abstract

Introduction: Infliximab, adalimumab, and certolizumab pegol (CZP) are approved for use in inducing andmaintaining remission inmoderate-to-severe Crohn's disease (CD). However, a significant proportion of patients either fail to respond to these agents or lose response over time. Prior failure is associated with lower rates of response to subsequent anti-TNF therapy. In patients who fail two anti-TNF agents, a choice exists between using a thirdanti TNF therapy vs. initiating natalizumab (NAT), an integrin inhibitor that acts through a distinct biologic mechanism. The cost-effectiveness of these two competing strategies in patients with loss of response to two prior anti-TNF therapies has not been examined. Methods: A decision analysis model was constructed to compare the performance of CZP as the third-line anti-TNF therapy vs. NAT in patients withmoderate-to-severe CD. Previously published estimates of efficacy of third-line anti-TNF therapy (Allez M, APT 2010) and NAT (Sandborn WJ, NEJM 2005) were used to inform the model. Costs were expressed in 2010 US dollars. A 1 year time frame was used for the analysis. The incremental cost-effectiveness ratio (ICER) was calculated and sensitivity analyses were performed by varying cost and efficacy estimates. Results: For the base case scenario, we assumed a response rate at 2 months of 61% for CZP among whom 54% were able to maintain response or remission at the end of the year (Allez M, APT 2010). From the ENACT trials, a 2 month response rate of 58% was estimated for NAT; 39% of these patients maintained remission at 12 months with 15% achieving clinical response. At the base case estimate, use of NAT was more effective (0.72 vs. 0.71 QALYs) but was associated with an incremental cost of $1,502 yielding an ICER of $120,976/QALY. For 2 month response rate with CZP of 50% or lower, NAT had an acceptable ICER at a willingness-to-pay threshold of $80,000/QALY or lower(Figure). Reduction in CZP costs by 25% yielded high ICER for NAT at all CZP response rates > 10%. In a hypothetical cohort of 100,000 patients, both strategies resulted in similar proportion of patients achieving clinical remission or response (61,051 with CZP compared to 60,111 with NAT) at the end of 1 year. Conclusion: In patients with moderateto-severe CD failing two-anti TNF therapies, using a third-anti TNF (CZP) appears to be a cost-effective strategy if response rates of at least 50% can be achieved at 2 months.