Cost-Effectiveness of Tight Control for Crohn's Disease With Adalimumab-Based Treatment: Economic Evaluation of the CALM Trial From a Canadian Perspective

Peter L Lakatos, Gilaad G Kaplan, Brian Bressler, Reena Khanna, Laura Targownik, Jennifer Jones, Yasmine Rahal, Kevin McHugh, Remo Panaccione, Peter L Lakatos, Gilaad G Kaplan, Brian Bressler, Reena Khanna, Laura Targownik, Jennifer Jones, Yasmine Rahal, Kevin McHugh, Remo Panaccione

Abstract

Crohn's disease (CD) is associated with reduced quality of life, increased absenteeism and high direct medical costs resulting from frequent hospitalizations and surgeries. Tumor necrosis factor-alpha inhibitors (TNFi's) have transformed the therapeutic landscape and enabled a shift from a symptom control to a treat-to-target strategy. The Effect of Tight Control Management on Crohn's Disease (CALM) trial demonstrated tight control (TC), with TNFi dose changes informed by biochemical markers of inflammation, achieved higher mucosal healing rates compared with conventional management (CM) based on symptoms. A Markov model compared TC and CM strategies from the perspective of the Canadian public payer using patient-observation data from the CALM trial. A regression model estimated weekly CD Activity Index-based transition matrices over a 5-year horizon and included covariates to improve extrapolation of outcomes beyond the 48-week trial assessment period. Costs of CD-related hospitalizations, biomarker tests and adalimumab injections were sourced from public data. Other direct medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Absenteeism was monetized and included in a sensitivity analysis. Over the 5-year time horizon, TC reduced hospitalization costs by 64% compared with CM. Other direct medical costs were reduced by 22%; adalimumab costs increased by 38%, generating an ICER of $35,168 per QALY gained. Absenteeism costs were reduced by 54%, and, when that was included in the model, TC became dominant compared with CM. Management of CD with TC is cost-effective compared with CM in Canada and is dominant if indirect costs associated with absenteeism are included. Trial registration number: NCT01235689.

Keywords: Adalimumab; Cost-utility analysis; Crohn’s disease; Tight control.

© The Author(s) 2022. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.

Figures

Figure 1.
Figure 1.
Structure of state transition model. Patients with Crohn’s disease may have different levels of disease activity, included as the CDAI-based health states in the model. Each model week, a patient was predicted to be in one of the health states and could transition from one health state to another based on transition probabilities derived from CALM trial data using a regression model. Hospitalization was included as a toll state. The health states determined patients’ costs, health utility and likelihood of hospitalization.
Figure 2.
Figure 2.
Results from a one-way sensitivity analysis of base-case analysis. Parameters (refer to Table 2 for values) are presented in descending order of model sensitivity. Bars that do not cross the vertical axis represent parameters with one variable only in the sensitivity analysis. Vertical dashed lines represent thresholds for dominance (long dashed lines) and willingness to pay (short dashed lines). SF-6D values derived from the CALM trial were used in the sensitivity analysis. CALM, Effect of Tight Control Management on Crohn’s Disease; CDAI, Crohn’s Disease Activity Index; CRP, C-reactive protein; ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-years; SF-6D, Short-Form 6-Dimension. ∗All costs are in 2020 Canadian dollars.
Figure 3.
Figure 3.
Impact of time horizon on ICER. The ICER was calculated using the base case scenario with only the time horizon changing. Horizontal dashed line represents the threshold for willingness to pay of $50,000∗ per QALY. ICER, incremental cost-effectiveness ratio; QALY, quality-adjusted life-years. ∗All costs are in 2020 Canadian dollars.
Figure 4.
Figure 4.
Cost-effectiveness acceptability curves representing the probability of cost-effectiveness of tight control versus clinical management excluding (reference case) and including absenteeism due to Crohn’s disease, at different willingness-to-pay thresholds. Results are depicted for the analysis excluding absenteeism (hashed lines) and including absenteeism (solid line). Results are based on the probabilistic sensitivity analysis, which included 1,000 second-order Monte Carlo simulations in which model variables were simultaneously varied. Vertical line depicts the $50,000 (dashed lines) willingness to pay threshold per QALY gained. ∗All costs are in 2020 Canadian dollars.

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