Cost-effectiveness model for on-demand treatment of hereditary angioedema (HAE) attacks

Background: Hereditary angioedema (HAE) is a rare C1-inhibitor (C1-INH) deficiency disease involving recurrent painful episodes of severe swelling that should be promptly treated. Aims: To determine cost and utility estimates for on-demand treatment of HAE attacks in order to better clarify and control expenses related to disease management. Methods: A decision-tree model included four comparators (ecallantide, icatibant, plasma-derived [pd] C1-INH, and recombinant human C1-INH [rhC1-INH]) and incorporated probabilities for self-administration vs healthcare provider administration, re-dosing, and hospitalization risk. Modeled costs comprised HAE therapies and healthcare system expenses. Effectiveness considered utility during attacks (0.51), no-attack baseline (0.83), and time to attack resolution. Overall drug cost and effectiveness per attack were used to estimate cost per quality-adjusted life year (QALY). Sensitivity analyses were performed to establish cost-effectiveness ranges. A budget impact model was developed for a health plan of 1 million (M) covered lives. Results: Costs and utility per attack were, respectively, $12,342 and 0.804 for rhC1-INH, $14,369 and 0.749 for icatibant, $13,993 and 0.759 for pdC1-INH, and $20,315 and 0.786 for ecallantide. At a mean annual attack rate of 26.9, cost per QALY was $402,769 for rhC1-INH, $475,942 for icatibant, $462,275 for pdC1-INH, and $666,153 for ecallantide. Re-dose rate was identified as a primary driver of cost-effectiveness variability. Estimated annual cost to the plan was $6.64 M for rhC1-INH, $7.73 M for icatibant, $7.53 M for pdC1-INH, and $10.93 M for ecallantide. A 5000-trial probabilistic sensitivity analysis (PSA) indicated that rhC1-INH was the most cost-effective in many scenarios, while ecallantide was the least cost-effective: mean costs (effectiveness) from PSA were $12,390 (0.786) for rhC1-INH, $14,132 (0.738) for icatibant, $13,050 (0.746) for pdC-1INH, and $20,286 (0.785) for ecallantide. Conclusions: This model demonstrated that rhC1-INH was the most cost-effective and ecallantide the least cost-effective on-demand HAE treatment and, overall, cost-effectiveness was substantially impacted by re-dosing rates. For icatibant, re-dosing rates of up to 44% to treat an HAE attack have been reported, and prescribing information allows up to three doses per 24-h period to treat a single attack. Driven by higher re-dosing rates, icatibant suffers from a higher per-attack drug cost and comparatively poor effectiveness.