Inibidor da C1 esterase derivado de plasma via subcutânea para profilaxia de crises de angioedema hereditário / Plasma-derived C1 esterase inhibitor subcutaneously for prophylaxis of hereditary angioedema crises

INTRODUÇÃO: O angioedema hereditário (AEH) é uma imunodeficiência primária do sistema complemento, e foi classificado como um erro inato da imunidade em decorrência da deficiência de inibidor de C1 esterase, proteína que controla as vias de ativação do complemento. Trata-se de doença com herança autossômica dominante, heterogeneidade de lócus e expressividade variável. A classificação mais atualizada do AEH agrupa os pacientes naqueles com deficiência do inibidor da C1- esterase (C1-INH), codificado pelo gene SERPING1 e naqueles C1-INH normal (anteriormente denominado de tipo III). O diagnóstico é realizado através do exame clínico (anamnese, exame físico e quadro clínico) e laboratorial (dosagem de C4 e de C1-INH), além de teste genético (presença de mutação patogênica em SERPING1) para confirmação. Embora AEH não tenha cura, há tratamento para a profilaxia e controle das crises. Atualmente, para o tratamento de profilaxia, o Protocolo Clínico e Diretrizes Terapêuticas (PCDT) do angioedema associado a deficiência de C1 esterase (C1-INH) do Ministério da Saúde, recomenda o uso de andrógenos atenuados, sendo o mais utilizado o danazol, e plasma fresco congelado para o tratamento de crises. PERGUNTA 1: O inibidor de C1 esterase via subcutânea é uma alternativa na

Living With Hereditary Angioedema in Australia: Findings From a National Observational Study Using Short Message Service to Monitor the Burden of Disease.

BACKGROUND: To understand the impact and burden of disease experienced by patients with hereditary angioedema (HAE). OBJECTIVE: To determine whether the use of short message service (SMS) to communicate with patients with HAE facilitates the collection of attack rate, medication use, and quality of life measurements. METHODS: Patients aged 12 years and older with doctor-confirmed HAE C1-inhibitor deficiency types I and II were invited to participate. We devised a novel method for monitoring attacks by using questions weekly via SMS to gain a more accurate picture of the burden of HAE in Australian patients in real time. RESULTS: A total of 2,648 weekly SMS messages were sent to 47 participants; 1,892 responses were received (71%). Participants reported 463 attacks across all treatment groups. Sixty percent of attacks were treated. Icatibant and C1-inhibitor concentrate were administered IV for 210 and 67 attacks, respectively. Of the 463 recorded attacks, 23 necessitated presentation to the hospital (5%), predominantly for facial and/or throat swelling. Several participants reported attacks (n = 186), which they chose not to treat. Most of those attacks were rated mildly severe. Twenty-one participants reported lost days owing to HAE attacks (44.7%). Fifty-eight attacks (17%) resulted in time away from work or school, equating to a total of 85.5 days lost. CONCLUSIONS: This study was a first of its kind, real-world, prospective, observational study of Australian patients living with HAE. Despite the availability of effective on-demand therapies, HAE remains burdensome. Wider access to safe and effective prophylactic therapies is needed for patients living with HAE.

Challenges in the management of hereditary angioedema in urban and rural settings: Results of a United States survey.

BACKGROUND: Caring for patients with hereditary angioedema (HAE), especially rural patients, has challenges. OBJECTIVE: To confirm experiences of allergy and immunology health professionals in diagnosing and treating patients with HAE, including those living in rural settings. METHODS: An online survey of 2996 members of the American College of Allergy, Asthma, and Immunology was conducted in April 13 to May 3, 2022. Eligible participants were association members (physician, fellow, or allied health professional members) currently practicing allergy or immunology, in the United States, seeing or treating at least 1 patient with HAE yearly. RESULTS: A total of 138 responders saw an average of 9 patients with HAE yearly; 12% of the patients resided in a rural area. They reported that 66% of their patients with HAE had type I, 15% type II, and 19% HAE C1nl-INH. Misdiagnosis was the top diagnostic challenge reported (82%). Inability to afford treatment was the top treatment challenge (76%). Other observations include the sentiment that patients with HAE with government insurance are at a disadvantage because it is not accepted by many specialists who treat HAE (64%) and that better payments for drugs from Medicaid and Medicare (57%) and better payments to providers from Medicaid and Medicare (49%) could better support the treatment of patients in rural settings. Responders expressed a preference for therapies administered at home (72%). Since the coronavirus disease 2019 pandemic, 86% of the respondents used telehealth for appointments occasionally. CONCLUSION: Our findings illustrate the challenge of diagnosing HAE, especially HAE C1nl-INH, and the economic challenges of treatment, which can be compounded for those living in rural areas. We provide a call to action for addressing several of these real challenges.

Epidemiology, Management, and Treatment Access of Hereditary Angioedema in the Asia Pacific Region: Outcomes From an International Survey.

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease with significant morbidity and mortality for which early diagnosis and effective therapy are critical. Many Asia Pacific (AP) countries still lack access to diagnostic tests and evidence-based therapies. Epidemiologic data from the AP is needed to formulate regional guidelines to improve standards of care for HAE. OBJECTIVE: To investigate the estimated minimal prevalence, needs, and potential interventions for the diagnosis and management of HAE in the AP. METHODS: A structured questionnaire was distributed to representative experts from member societies of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. Patient profiles and the presence of diagnostic facilities or tests, regional and national HAE guidelines, and patient support groups were reported and compared. RESULTS: Completed questionnaires were received from 14 representatives of 12 member countries and territories, representing 46% of the world population. Overall minimal prevalence of HAE in the AP region was 0.02/100,000 population, with significant heterogeneity across different centers. Only one-half and one-third had registered on-demand and prophylactic medications, respectively. Few had patient support groups (58%) or regional guidelines (33%), and their existence was associated with the availability of HAE-specific medications. Availability of C1-inhibitor level testing was associated with a lower age at HAE diagnosis (P = .017). CONCLUSIONS: Hereditary angioedema in the AP differs from that in Western countries. Hereditary angioedema-specific medications were registered in only a minority of countries and territories, but those with patient support groups or regional guidelines were more likely to have better access. Asia Pacific-specific consensus and guidelines are lacking and urgently needed.

Addressing the individualized needs in hereditary angioedema: managed care strategies to optimize access to care.

Hereditary angioedema (HAE) is a serious, potentially fatal disease of recurrent swelling of various subcutaneous and submucosal tissues throughout the body. Swelling is mediated by uncontrolled regulation of bradykinin, making it pathologically distinct from other forms of angioedema. Diagnosis can be challenging, but distinctions in clinical presentation and laboratory studies can confirm clinical suspicion. Though the disease is rare, the socioeconomic burden of living with and treating HAE is significant for patients and healthcare systems. As a result, there has been a dramatic expansion of treatment options specifically designed for HAE in recent years. Novel treatments are effective in treating swelling attacks, preventing recurrence, and improving patient quality of life. However, significant differences in the risks, benefits, and cost of treatments must be weighed in the determination of clinical protocols to determine optimal utilization of healthcare resources.

Indirect Comparison of Lanadelumab and Intravenous C1-INH Using Data from the HELP and CHANGE Studies: Bayesian and Frequentist Analyses.

BACKGROUND: Hereditary angioedema (HAE) with C1-esterase inhibitor (C1-INH) deficiency is a rare disease associated with painful, potentially fatal swelling episodes affecting subcutaneous or submucosal tissues. HAE attacks recur with unpredictable severity and frequency throughout patients' lives; long-term prophylaxis is essential for some patients. In the absence of head-to-head studies, indirect treatment comparison (ITC) of long-term prophylactic agents is a valid approach to evaluate comparative efficacy. METHODS: We conducted an ITC using data from the placebo-controlled HELP study (assessing patients receiving lanadelumab 300 mg every 2 or 4 weeks) and the 12-week, parallel arm, crossover CHANGE study (assessing intravenous C1-INH). Outcomes of interest were attack rate ratio (ARR) and time to attack after day 0 (TTA0) and after day 70 (TTA70). Two ITC methodologies were used: a Bayesian approach using study results to update non-informative prior distributions to posterior distributions on relative treatment effects, and a frequentist approach using patient-level data from HELP and CHANGE to generate Poisson regressions (for ARR) and Cox models (for TTA0 and TT70). RESULTS: Both Bayesian and frequentist analyses suggested that lanadelumab reduced HAE attack rate by 46-73% versus intravenous C1-INH. Relative to intravenous C1-INH, risk of first attack after day 0 was comparable between intravenous C1-INH and both lanadelumab doses; risk of first attack after day 70 was reduced by 81-83% with lanadelumab 300 mg every 2 weeks, compared with C1-INH. CONCLUSIONS: Findings from these two ITC methodologies support the favorable efficacy of lanadelumab in reducing the HAE attack rate and extending attack-free intervals in patients with HAE.

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.

Prospective Analysis in Patients With HAE Under Prophylaxis With Lanadelumab: A Real-life Experience.

BACKGROUND AND OBJECTIVES: Patients with the rare disease hereditary angioedema (HAE) suffer from recurrent acute attacks of edema. There is no curative therapy, but the frequency of attacks and quality of life of severely affected patients can be improved by prophylactic therapy. The monoclonal antibody lanadelumab has been approved for routine prophylaxis in patients with HAE since November 2018. PATIENTS AND METHODS: In this prospective assessment, a long-term therapy with lanadelumab was initiated in 12 adult patients with HAE. We analyzed their course of disease 6 months after the start of long-term prophylactic therapy using a validated quality-of-life questionnaire and evaluated the frequency and severity of attacks as well as side effects. Furthermore, the therapy with lanadelumab was compared with the previous medication. RESULTS: To date, our study is the first prospective quality of life analysis in HAE patients under treatment with lanadelumab in real life conditions. Mean attack frequencies were reduced from 6.4 to 0.3 attacks per month and patient in our cohort (P<0.0001). No severe attacks occurred under lanadelumab prophylaxis. In all patients, quality of life increased significantly. CONCLUSIONS: Lanadelumab is an effective but expensive long-term prophylaxis for HAE patients. A favorable side-effect profile has been shown. J Drugs Dermatol. 2020;19(10):978-983. doi:10.36849/JDD.2020.5269.

Patient-reported burden of hereditary angioedema: findings from a patient survey in the United States.

BACKGROUND: Hereditary angioedema (HAE) with C1-inhibitor deficiency is associated with painful, potentially fatal attacks affecting subcutaneous or submucosal tissues. OBJECTIVE: To evaluate HAE burden from the patients' perspective. METHODS: This was a noninterventional survey of patients with HAE in the United States, conducted from March 17 to April 28, 2017. Patients were recruited through the US Hereditary Angioedema Association. Key eligibility criteria included the following: (1) aged 18 years and older, (2) self-reported physician diagnosis of HAE type I or II, (3) 1 or more HAE attacks or prodromal symptoms within the last year, and (4) receipt of HAE medication for an attack within the last 2 years. Descriptive analyses were conducted. RESULTS: A total of 445 patients completed the survey. Most patients (92.8%) were aged 18 to 64 years with HAE type I (78.4%) and had a positive family history (78.4%). Mean (SD) ages at symptom onset and diagnosis were 12.5 (9.1) and 20.1 (13.7) years, respectively. Most patients (78.7%) experienced an attack within the past month. The abdomen (58.0%) and extremities (46.1%) were commonly affected sites; pain (73.9%) and abdominal (57.0%) and nonabdominal (55.1%) swelling were frequently reported symptoms. Most patients (68.5%) had received or were currently receiving long-term prophylaxis. Most patients (88.8%) reported visiting allergists or immunologists, whereas 9.2% visited emergency departments or urgent care clinics. Per the Hospital Anxiety and Depression Scale, 49.9% and 24.0% of respondents had anxiety and depression, respectively. Mean Hereditary Angioedema-Quality of Life scores were generally lower with higher attack frequency. General health was "poor" or "fair" for 24.8% of patients. Mean (SD) percentage impairments were 5.9% (14.1%) for absenteeism, 23.0% (25.8%) for presenteeism, 25.4% (28.1%) for work productivity loss, and 31.8% (29.7%) for activity impairment. CONCLUSION: Despite treatment advances, patients with HAE in the United States continue to have a high burden of illness.

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.

Health-related quality of life and its risk factors in Chinese hereditary angioedema patients.

BACKGROUND: Hereditary angioedema (HAE) is a rare but serious condition characterized by unpredictable and recurrent attacks affecting the skin and mucosa. HAE has wide-ranging impacts on the health-related quality of life (HRQoL) of patients. This study aims to assess the HRQoL of Chinese patients with HAE using the 36-item Short Form Health Survey (SF-36v2) and to explore potential risk factors for low HRQoL. METHODS: A total of 104 patients (47 male and 57 female) over age 18 living in China with a known diagnosis of HAE due to C1-INH deficiency completed the SF-36v2 (generic HRQoL questionnaire). The results were compared to Chinese population norms. Subgroup analysis and logistic regression were used to interpret the data. RESULTS: SF-36v2 showed a significant reduction in all dimensions of HRQoL (p < 0.001) in patients with HAE compared with the general Chinese population. Female patients reported significantly lower bodily pain (BP) (p = 0.039) and physical component scores (PCSs) (p = 0.027) than male patients. Patients with mucosal edema tended to report lower role-physical (RP) limitations (p = 0.031) than patients with only skin edema. There were no differences between the mean scores of the SF-36 in relation to disease subtype, age, disease severity and long-term prophylaxis. Among female patients on long-term prophylaxis, social functioning (SF) (r = - 0.404, p = 0.010), role-emotional (RE) (r = - 0.320, p = 0.044) and mental component scores (MCSs) (r = - 0.313, p = 0.049) were negatively correlated with danazol dosage. A correlation between decreased disease control and decreased HRQoL scores was found, although the correlation was not significant in terms of RE or mental health (MH) scores. The logistic regression model revealed uncontrolled disease to be a risk factor for a low PCS (odds ratio 10.77, 95% confidence interval [CI] 1.78-65.06; p = 0.010) and laryngeal edema to be a risk factor for a low MCS (odds ratio 4.75, 95% CI 1.09-20.69; p = 0.038). CONCLUSIONS: Chinese HAE patients reported significantly lower HRQoL scores than the general population. Unsatisfactory disease control is a risk factor for decreased PCSs. Laryngeal edema is a risk factor for decreased MCSs.

The Effectiveness and Value of Lanadelumab and C1 Esterase Inhibitors for Prophylaxis of Hereditary Angioedema Attacks.

DISCLOSURES: Funding for this summary was contributed by the Laura and John Arnold Foundation, Blue Shield of California, and California Health Care Foundation to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, AHIP Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Cambia Health Solutions, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Prime Therapeutics, Sanofi, Spark Therapeutics, Health Care Service Corporation, Editas, Alnylam, Regeneron, Mallinkrodt, Biogen, HealthPartners, and Novartis. Agboola, Dreitlein, and Pearson are ICER employees. Lin reports personal fees from ICER, during the conduct of this study, and grants from the National Institutes of Health and the California Department of Insurance, outside the submitted work. Carlson and Lubinga report grants from ICER, during the conduct of this study.

Update on the Use of C1-Esterase Inhibitor Replacement Therapy in the Acute and Prophylactic Treatment of Hereditary Angioedema.

In the vast majority of patients with hereditary angioedema (HAE), angioedema attacks are due to the quantitative or functional deficiency of C1-esterase inhibitor (C1-INH), which leads to increased vascular permeability and unregulated release of bradykinin. Exogenous administration of C1-INH is a rational way to restore the concentration and functional activity of this protein, regulate the release of bradykinin, and attenuate or prevent subcutaneous and submucosal edema associated with HAE. Recent international guidelines for the management of HAE include C1-INH as an option for acute treatment of HAE. In addition, these guidelines recommend C1-INH as first-line treatment for long-term prophylaxis and as the therapy of choice for short-term/preprocedural prophylaxis. Several C1-INH products are available, with approved indications varying across regions. For the acute treatment of HAE, both plasma-derived and recombinant C1-INH formulations have been shown to be effective and well tolerated in adolescents and adults with HAE, with onset of relief within 30 min to a few hours. Plasma-derived C1-INH is approved for use in children, and recombinant C1-INH is being evaluated in this population. Intravenous (IV) and subcutaneous (SC) formulations of C1-INH have been approved for routine prophylaxis to prevent HAE attacks in adolescents and adults. Both formulations when administered twice weekly have been shown to reduce the frequency and severity of HAE attacks. The SC formulation of C1-INH obviates the need for repeated venous access and may facilitate self-administration of HAE prophylaxis at home, as recommended in HAE treatment guidelines. As with most rare diseases, the costs of HAE treatment are high; however, the development of additional acute and prophylactic medications for HAE may result in competitive pricing and help drive down the costs of HAE treatment.

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.

Treatment of hereditary angioedema due to C1 inhibitor deficiency in Argentina.

The benefits of the worldwide approval of new drugs for the treatment of acute C1-INH-HAE attacks may still not reach all patients. Identifying the current barriers in the access to medication, as well as conducting a detailed assessment of the progress in this area, is essential to achieve universal treatment. Two hundred and twenty five patients registered in the Argentina Hereditary Angioedema Patient Association (AHAEPA) were randomly selected and invited to participate in a web based questionnaire on accessibility to icatibant and pdC1-INH, self-treatment, delay to treatment, and coverage. The data retrieved was compared to our previous reports in 2008 and 2013. We collected 156/225 answers. One hundred and eighteen (76%) patients have either pdC1-INH (n = 86), icatibant (n = 10) or both (n = 22), while 38 (24%) do not have access to treatment. In 2008, 26% had access while 82% had it in 2013. Thirty-two subjects (22%) self-inject themselves, similar to 29% in 2013, even though between studies, widespread self-injection training activities have taken place. However, considering injections by proxy, home treatment reached 56%. Only half of the patients decide to receive treatment early during the attack. Ninety-nine patients (63%) have full coverage, thirty (19%) have no coverage at all and the rest only obtain partial reimbursement. Twenty-nine families (31%) share a single treatment dose of the medication, better than 36% in 2013. Argentina's C1-INH-HAE patients had a sustained improvement in their access to medication. Efforts should continue to further improve accessibility and optimal management of HAE acute attacks to all patients in the country.

Treatment of hereditary angioedema due to C1 inhibitor deficiency in Argentina

The benefits of the worldwide approval of new drugs for the treatment of acute C1-INH-HAE attacks may still not reach all patients. Identifying the current barriers in the access to medication, as well as conducting a detailed assessment of the progress in this area, is essential to achieve universal treatment. Two hundred and twenty five patients registered in the Argentina Hereditary Angioedema Patient Association (AHAEPA) were randomly selected and invited to participate in a web based questionnaire on accessibility to icatibant and pdC1-INH, self-treatment, delay to treatment, and coverage. The data retrieved was compared to our previous reports in 2008 and 2013. We collected 156/225 answers. One hundred and eighteen (76%) patients have either pdC1-INH (n = 86), icatibant (n = 10) or both (n = 22), while 38 (24%) do not have access to treatment. In 2008, 26% had access while 82% had it in 2013. Thirty-two subjects (22%) self-inject themselves, similar to 29% in 2013, even though between studies, widespread self-injection training activities have taken place. However, considering injections by proxy, home treatment reached 56%. Only half of the patients decide to receive treatment early during the attack. Ninety-nine patients (63%) have full coverage, thirty (19%) have no coverage at all and the rest only obtain partial reimbursement. Twenty-nine families (31%) share a single treatment dose of the medication, better than 36% in 2013. Argentina's C1-INH-HAE patients had a sustained improvement in their access to medication. Efforts should continue to further improve accessibility and optimal management of HAE acute attacks to all patients in the country.

La aprobación mundial de los medicamentos para el ataque agudo del angioedema hereditario (HAE) no beneficia a todos los pacientes. Es necesario conocer las barreras de acceso a la medicación para el tratamiento universal. Doscientos veinticinco pacientes, registrados en la Asociación de Pacientes con Angioedema Hereditario (AHAEPA), fueron encuestados por internet acerca de su accesibilidad al icatibant y al concentrado del inhibidor de C1 (pdC1-INH), a la auto inyección de la medicación, al retraso del tratamiento y a la cobertura del medicamento. Comparamos esta información con la obtenida en nuestros estudios de 2008 y 2013. Recolectamos 156/225 respuestas. Ciento dieciocho (76%) pacientes tienen pdC1-INH (n = 86), icatibant (n = 10) o ambos (n = 22), mientras que 38 (24%) no tienen medicación. En 2008, 26% tenían acceso y en 2013, 82%. Treinta y dos (22%) se autoinyectan la medicación, similar al 29% en 2013. Sumando las aplicaciones por profesionales de la salud o familiares en la casa, el tratamiento fuera de las instituciones médicas alcanza el 56%. Solo la mitad decide tratarse tempranamente. Noventa y nueve (63%) tiene cobertura del 100%, 30 (19%) no tiene ningún tipo de cobertura, y el resto la tiene en forma parcial. Veintinueve familias (31%), solo tienen una dosis de tratamiento para todos, mejor que el 36% en 2013. Los pacientes con C1-INH-HAE han tenido una mejoría sustancial en el acceso a la medicación. Igualmente, los esfuerzos deben continuar para mejorar la accesibilidad y tratamiento óptimo de todos.

Anabolic androgen use in the management of hereditary angioedema: Not so cheap after all.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare, life-threatening disease that imposes a significant burden on affected patients. 17α-alkylated androgens (anabolic androgens) decrease attack frequency and severity but carry the risk of potentially serious dose-related adverse effects. Despite the emergence of targeted therapies for HAE, continued anabolic androgen use has been driven in part by their low cost. OBJECTIVE: To examine the hidden cost of anabolic androgen use related to the risk of developing non-HAE comorbidities. METHODS: Patients with HAE were identified in the Southern California Kaiser Permanente database using clinical and laboratory findings compatible with HAE. These patients were stratified into anabolic androgen exposed and nonexposed groups. Matched controls were selected from the Kaiser database who did not have HAE or anabolic androgen exposure. Using multivariate analysis, we determined the number of non-HAE comorbidities linked to anabolic androgen use. We next determined the association between dosing and increasing exposure to anabolic androgens and the likelihood of having various comorbidities. RESULTS: Patients with HAE exposed to anabolic androgens had a 28% increase (P = .04) in non-HAE comorbidities when compared with their matched (nonexposed) controls. With each gram per month increase in exposure, a 12% increase in non-HAE comorbidities is observed (P < .01). The most commonly occurring non-HAE comorbidities were psychiatric, muscle cramps, obesity, and hyperlipidemia. CONCLUSION: Our data suggest that long-term anabolic androgen use enhances the risk of developing comorbid health conditions, thus amplifying the cost of care. Our report provides additional support for the preferred use of newer, targeted therapies for the management of HAE.