Assessing the cost and quality-of-life impact of on-demand-only medications for adults with hereditary angioedema.

Background: Novel subcutaneous (SC) prophylactic therapies are transforming the treatment landscape of hereditary angioedema (HAE). Although questions are being raised about their cost, little attention has been paid to the cost and quality of life (QoL) impact of using on-demand-only medications. Objective: We assessed the overall economic burden of on-demand-only treatment for HAE and compared patient QoL with patients who received novel SC prophylactic therapies. Methods: US Hereditary Angioedema Association members were invited to complete an anonymous online survey to profile attack frequency, treatment use, and the presence of comorbidities as well as economic and socioeconomic variables. We modeled on-demand treatment costs by using net pricing of medications in 2018, indirect patient and caregiver costs, and attack-related direct billed costs for emergency department admissions, physician office visits, and/or hospitalizations. QoL was assessed by using the Angioedema Quality of Life questionnaire. Results: A total of 1225 patients (31.4%) responded. Of these, 737 adults with HAE (type I or II) met the inclusion criteria and completed the survey. Per patient/year direct costs associated with modeled on-demand-only treatment totaled $363,795, with additional indirect socioeconomic costs of $52,576 per patient/year. The greatest improvement in QoL was seen in patients who used novel SC prophylactic therapies, with a 59.5% (p < 0.01) improvement in median impairment scores versus on-demand-only treatment. In addition, patients who used novel SC prophylactic therapies reported a 77% reduction in the number of attacks each year when compared with those who used on-demand-only treatment. Conclusion: Our real-world patient data showed the cost and QoL burden of HAE treatment with on-demand-only therapy. Use of novel SC prophylaxis can lead to sizeable reductions in attack frequency and statistically significant and clinically relevant improvements in QoL. These data could be useful to clinicians and patients as they consider therapy options for patients with HAE.

Modeling Cost-Effectiveness of On-Demand Treatment for Hereditary Angioedema Attacks.

BACKGROUND: Hereditary angioedema (HAE) is a rare C1-inhibitor (C1-INH) deficiency disease. Low levels of functional C1-INH can lead to recurrent attacks of severe swelling occurring in areas such as the limbs, face, gastrointestinal tract, and throat. These attacks are both painful and disabling and, if not treated promptly and effectively, can result in hospitalization or death. Agents targeting the specific physiologic pathway of HAE attacks can offer improved outcomes with limited side effects compared with nonspecific therapies. However, these treatments display varying efficacy in HAE patients, including the need to redose or seek additional care if the treatment does not resolve symptoms effectively. OBJECTIVE: To analyze the expected cost and utility per HAE attack when treated on-demand with HAE therapies indicated for the treatment of acute attacks. METHODS: A decision-tree model was developed using TreeAge Pro software. Four on-demand HAE treatments were included: ecallantide, icatibant, plasma-derived (pd)C1-INH, and recombinant human (rh)C1-INH. The model uses probabilities for redosing, self-administration versus health care provider administration, and risk of hospitalization. Costs within the model consisted of the HAE treatments and associated health care system expenses. Nonattack baseline utility and attack utility were implemented for effectiveness calculations; time to attack resolution was considered as well. Effectiveness and overall costs per attack were calculated and used to estimate cost per quality-adjusted life-year (QALY). Variability and ranges in cost-effectiveness were determined using probabilistic sensitivity analyses. Finally, a budget impact model for a health plan with 1 million covered lives was also developed. RESULTS: The base case model outputs show costs and calculated effectiveness per attack at $12,905 and 0.806 for rhC1-INH, $14,806 and 0.765 for icatibant, $14,668 and 0.769 for pdC1-INH, and $21,068 and 0.792 for ecallantide, respectively. Cost per QALY was calculated using 26.9 attacks per person-year, leading to results of $420,941 for rhC1-INH, $488,349 for icatibant, $483,892 for pdC1-INH, and $689,773 for ecallantide. Sensitivity analyses demonstrate that redose rates (from 3% for rhC1-INH to 44% for icatibant) are a primary driver of variability in cost-effectiveness. Annual health plan costs from the budget impact model are calculated as $6.94 million for rhC1-INH, $7.97 million for icatibant, $7.90 million for pdC1-INH, and $11.33 million for ecallantide. CONCLUSIONS: Accounting for patient well-being and additional cost components of HAE attacks generates a better estimation of cost-effectiveness than drug cost alone. Results from this model indicate that rhC1-INH is the dominant treatment option with lower expected costs and higher calculated effectiveness than comparators. Further analyses reinforce the idea that low redose rates contribute to improved cost-effectiveness. DISCLOSURES: Funding support was contributed by Pharming Healthcare. Relan and Adams are employed by Pharming Healthcare. Tyson and Magar are employed by AHRM, which received fees to perform the analysis and develop the manuscript. Bernstein reports grants, personal fees, and nonfinancial support from Shire, CSL Behring, and Pharming Healthcare; grants and personal fees from Biocryst; and nonfinancial support from HAEA, unrelated to this study.

Costs and effects of on-demand treatment of hereditary angioedema in Italy: a prospective cohort study of 167 patients.

OBJECTIVES: To explore treatment behaviours in a cohort of Italian patients with hereditary angioedema due to complement C1-inhibitor deficiency (C1-INH-HAE), and to estimate how effects and costs of treating attacks in routine practice differed across available on-demand treatments. DESIGN: Cost analyses and survival analyses using attack-level data collected prospectively for 1 year. SETTING: National reference centre for C1-INH-HAE. PARTICIPANTS: 167 patients with proved diagnosis of C1-INH-HAE, who reported data on angioedema attacks, including severity, localisation and duration, treatment received, and use of other healthcare services. INTERVENTIONS: Attacks were treated with either icatibant, plasma-derived C1-INH (pdC1-INH) or just supportive care. MAIN OUTCOME MEASURES: Treatment efficacy in reducing attack duration and the direct costs of acute attacks. RESULTS: Overall, 133 of 167 patients (79.6%) reported 1508 attacks during the study period, with mean incidence of 11 attacks per patient per year. Only 78.9% of attacks were treated in contrast to current guidelines. Both icatibant and pdC1-INH significantly reduced attack duration compared with no treatment (median times from onset 7, 10 and 47 hours, respectively), but remission rates with icatibant were 31% faster compared with pdC1-INH (HR 1.31, 95% CI 1.14 to 1.51). However, observed treatment behaviours suggest patterns of suboptimal dosing for pdC1-INH. The average cost per attack was €1183 (SD €789) resulting in €1.58 million healthcare costs during the observation period (€11 912 per patient per year). Icatibant was 54% more expensive than pdC1-INH, whereas age, sex and prophylactic treatment were not associated to higher or lower costs. CONCLUSIONS: Both icatibant and pdC1-INH significantly reduced attack duration compared with no treatment, however, icatibant was more effective but also more expensive. Treatment behaviours and suboptimal dosing of pdC1-INH may account for the differences, but further research is needed to define their role.

Hereditary angioedema treatment options: the availability of new therapies.

Hereditary angioedema (HAE) is a potentially life-threatening autosomal dominant disease characterized by recurrent episodes of oedema, commonly occurring in the skin, abdomen, and upper respiratory tract. After many years during which limited treatment options were available, a range of newer therapies with proven efficacy have been approved in Europe by the European Commission for the treatment of HAE attacks. However, due to differing legislation and financial restrictions, these treatment options are not available in all countries. Home therapy and self-administration of treatment are recommended in order to minimize the burden of disease upon the patient, with the ideal treatment option being effective, well-tolerated, and easy to prepare and administer. Recently, the Hereditary Angioedema International Working Group (HAWK) consensus recommended early, on-demand treatment for HAE. This article reviews the current treatment options available, and considers the need for treatment guidelines to recommend the appropriate therapy.