Androgen transition and management of hereditary angioedema long-term prophylaxis in real life: a single-center case series.

BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that manifests clinically as recurrent episodes of swelling affecting multiple anatomical locations. Long-term prophylaxis (LTP) aims to control the disease by preventing HAE attacks. Previously, treatments such as attenuated androgens have been used for LTP, but they have an unfavorable adverse effect profile. Today, these limitations may be overcome by patients transitioning to newer, targeted therapies including oral berotralstat and subcutaneous lanadelumab. This case series reports the transition process between different prophylactic therapies in a family with HAE in a real-world setting. RESULTS: Four adult patient cases from the same family who underwent transitions in HAE prophylaxis are presented. Three were female and one male. Two patients who transitioned to berotralstat were initially prescribed attenuated androgens. Two patients were not taking LTP at the time of initiating targeted treatment but had previously been prescribed tranexamic acid. The length of transition varied between the patients, with the longest time taken to stabilize on new therapy being 26 months. All patients received regular follow-up in person or by telephone and all four required an adjustment from their initial treatment plan. CONCLUSIONS: Transitioning between LTP in HAE may help improve control of attacks, avoid unwanted adverse effects, or better cater to individual patient preferences. Newer targeted therapies have been shown to be effective and should be discussed with patients. Shared decision-making is a tool that can aid these discussions. The transition journey between LTP therapies in HAE may not be straightforward and is specific to each patient. Physicians should consider complicating factors such as patient anxieties around changing treatment, adverse effects, preferred routes of administration, and speed of transition. Following patients closely during the transition period helps identify any issues, including difficulties with treatment adherence, and may allow the transition plan to be adapted when necessary.

A quantitative systems pharmacology model of plasma kallikrein-kinin system dysregulation in hereditary angioedema.

Hereditary angioedema (HAE) due to C1-inhibitor deficiency is a rare, debilitating, genetic disorder characterized by recurrent, unpredictable, attacks of edema. The clinical symptoms of HAE arise from excess bradykinin generation due to dysregulation of the plasma kallikrein-kinin system (KKS). A quantitative systems pharmacology (QSP) model that mechanistically describes the KKS and its role in HAE pathophysiology was developed based on HAE attacks being triggered by autoactivation of factor XII (FXII) to activated FXII (FXIIa), resulting in kallikrein production from prekallikrein. A base pharmacodynamic model was constructed and parameterized from literature data and ex vivo assays measuring inhibition of kallikrein activity in plasma of HAE patients or healthy volunteers who received lanadelumab. HAE attacks were simulated using a virtual patient population, with attacks recorded when systemic bradykinin levels exceeded 20 pM. The model was validated by comparing the simulations to observations from lanadelumab and plasma-derived C1-inhibitor clinical trials. The model was then applied to analyze the impact of nonadherence to a daily oral preventive therapy; simulations showed a correlation between the number of missed doses per month and reduced drug effectiveness. The impact of reducing lanadelumab dosing frequency from 300 mg every 2 weeks (Q2W) to every 4 weeks (Q4W) was also examined and showed that while attack rates with Q4W dosing were substantially reduced, the extent of reduction was greater with Q2W dosing. Overall, the QSP model showed good agreement with clinical data and could be used for hypothesis testing and outcome predictions.

The real life experience goes on: update after 4 years on the first cohort treated with lanadelumab at our center.

Introduction: Lanadelumab is a first-line long-term prophylaxis (LTP) in hereditary angioedema (HAE). Real-life data on its long-term efficacy and safety are limited. It is unknown whether patients using lanadelumab need short-term prophylaxis (STP). Objectives: To provide 4-year follow-up data for our first 34 patients treating with lanadelumab. Methods: Patients were assessed for their current injection interval, attacks, treatment satisfaction, disease control (AECT), quality of life impairment (AE-QoL), events that can induce attacks, and the use of STP since the start of their treatment with lanadelumab. Results: Of 34 patients who started lanadelumab treatment, 32 were still using it after 4 years, with a median injection interval of 33 (range 14-90) days. HAE patients (n=28) reported longer intervals, i.e. 35 (14-90) days, than patients with angioedema due to acquired C1 inhibitor deficiency (n=4, 23 (14-31) days). With their current injection intervals, used for a mean duration of 29 ± 17 months, patients reported a yearly attack rate of 0.3 ± 0.1. More than 70% of patients were attack-free since starting their current injection interval. All patients reported well-controlled disease, i.e. ≥10 points in the AECT; 21 patients had complete control (16 points). AE-QoL scores improved further compared to our initial report, most prominently in the fears/shame domain (-6 points). Treatment satisfaction was very high. No angioedema occurred after 146 of 147 potentially attack-inducing medical procedures without STP. Conclusions: Our results demonstrate the long-term efficacy and safety of lanadelumab in real-life and question the need for STP in patients who use effective LTP.

Clinical Experience with Berotralstat in Patients with Hereditary Angioedema with Normal C1-Esterase Inhibitor: A Commented Case Series.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by potentially life-threatening episodes of swelling. Most HAE cases are caused by deficient (type I) or dysfunctional (type II) C1-esterase inhibitor (C1-INH) protein. However, some patients present with a subtype of HAE that is associated with normal plasma levels of functional C1-INH protein and complement component 4 (HAE-nC1INH). Treatment of HAE-nC1INH is driven by clinical experience as robust clinical trial data to inform treatment decisions are lacking in this population. This retrospective case series assessed clinical features and treatment outcomes in 15 patients with HAE-nC1INH who initiated long-term prophylaxis with oral berotralstat 150 mg once daily as part of their disease management pathway. Most patients were female (93%), with a median age of 49 years. All patients experienced abdominal swelling attacks. On average, patients tried a mean of 4 different treatments for their HAE, including berotralstat. Although most patients associated prophylactic and on-demand medications that target the bradykinin pathway with improvements in the frequency and/or severity of attacks, treatment outcomes varied considerably between patients, highlighting the importance of a personalized approach to disease management. In this case series, berotralstat was an effective prophylactic treatment option in most patients with HAE-nC1INH. Further studies are required to demonstrate the potential efficacy, safety, and impact on quality of life of currently approved HAE therapies in patients with HAE-nC1INH.

Effect of lanadelumab on attack frequency and QoL in Japanese patients with hereditary angioedema: Report of five cases.

Lanadelumab, a recombinant human anti-kallikrein monoclonal antibody, is recommended as the first-line option for long-term prophylaxis (LTP) in hereditary angioedema (HAE). However, the efficacy of lanadelumab and its effects on the quality of life (QoL) in Japanese HAE patients using real-world data have not been reported. Herein, we report the outcomes of five HAE patients who were treated with lanadelumab at two Japanese institutions. We retrospectively collected data on attack frequency and on-demand treatment frequency using an angioedema quality of life (AE-QoL) questionnaire. Our data corresponded to five Japanese HAE patients who started lanadelumab treatment: four with HAE due to C1-inhibitor deficiency (HAE-1) and one with HAE with a normal C1-inhibitor (HAE-nC1-INH). Two HAE-1 patients showed a reduction in both attacks and number of on-demand treatments. The other HAE-1 patients had an increase in the number of on-demand treatments, although there was no apparent reduction in attacks. The HAE-nC1-INH patient showed a slight increase in both attacks and number of on-demand treatments. Only one HAE-1 patient discontinued treatment after 1 month owing to side effects, including dizziness and headache. All four who continued treatment showed improved AE-QoL total and domain scores. Therefore, in this study, using real-world data, we demonstrated that lanadelumab reduced attack frequency and improved QoL in Japanese HAE patients.

Patient-level indirect treatment comparison of lanadelumab versus pdC1-INH i.v. in hereditary angioedema patients: PATCH study.

BACKGROUND: Hereditary angioedema (HAE) is an autosomal dominant inherited disease in which patients suffer from local attacks primarily affecting skin and gastrointestinal tract, and sometimes even the upper respiratory tract leading to asphyxiation. Since head-to-head trials between authorized treatments are lacking, this study compares efficacy and safety of lanadelumab and intravenous plasma-derived C1-esterase inhibitor (pdC1-INH i.v.) in HAE patients on long-term prophylaxis by means of an indirect treatment comparison. METHODS: Efficacy and safety of lanadelumab against pdC1-INH i.v. were analyzed in a fully prespecified indirect comparison based on individual patient data (n = 231) from the HELP and CHANGE clinical trials. Primary and secondary efficacy endpoints were compared using a generalized linear model for count data. Confounding variables were identified a priori via systematic literature research and validated by clinical experts. Adjustment of confounders was implemented using a conditional regression model. RESULTS: Lanadelumab showed a statistically significant improvement in reduction of HAE attack rates compared to pdC1-INH i.v. across multiple endpoints: Monthly attack rate of patients treated with lanadelumab was less than half compared to pdC1-INH i.v. (Rate ratio: 0.486; 95% CI: 0.253, 0.932). Monthly rate of laryngeal attacks was found to be five times lower for lanadelumab (Rate ratio: 0.2; 95% CI: 0.044, 0.915) and monthly rate of acute treated HAE attacks among lanadelumab patients was about one third of the attack rate of pdC1-INH i.v. patients (Rate ratio: 0.366; 95% CI: 0.185, 0.727). CONCLUSION: This study contributes to current knowledge in the treatment of HAE by indicating a statistically significant reduction of HAE attacks under lanadelumab compared to pdC1-INH i.v.

Lanadelumab in Patients 2 to Less Than 12 Years Old With Hereditary Angioedema: Results From the Phase 3 SPRING Study.

BACKGROUND: Symptoms of hereditary angioedema (HAE) often first occur during childhood, and HAE attacks in children can be severe and substantially affect health-related quality of life (HRQoL). However, there are no approved long-term prophylaxis treatments for children aged less than 6 years. OBJECTIVE: The SPRING Study (NCT04070326) evaluated the safety, pharmacokinetics, and efficacy of lanadelumab and HRQoL in patients aged 2 to less than 12 years. METHODS: Over 52 weeks of treatment, patients aged 2 to less than 6 years received lanadelumab 150 mg every 4 weeks (Q4W) and patients aged 6 to less than 12 years received 150 mg every 2 weeks (Q2W) but could switch to Q4W if they were attack-free for 26 weeks. RESULTS: We enrolled 21 patients (aged 2 to less than 6 years: n = 4; aged 6 to less than 12 years: n = 17), 20 of whom completed the study. There were no reported serious treatment-emergent adverse events or discontinuations resulting from such events. Treatment-emergent adverse events were reported for 17 patients (81.0%). The most common TEAE was injection site pain. Overall systemic exposure was comparable for both age groups. The mean (SD) attack rate during treatment decreased by 94.8% from baseline (1.84 [1.53] to 0.08 [0.17] attacks/mo), and 16 (76.2%) patients were attack-free. The attack rate reduction in both age groups was similar during the first 26-week fixed-dosing treatment. Seven patients switched from Q2W to Q4W and remained attack-free. A large, clinically meaningful increase in the Pediatric Quality of Life Inventory Generic Core Scale Total Score and a large increase in the Pediatric Quality of Life Inventory Generic Core Scale-Family Impact Module Total Score from baseline to end of study (better HRQoL) were observed. CONCLUSIONS: Findings support safety, efficacy, and improved HRQoL with lanadelumab 150 mg Q2W and Q4W regimens for the prevention of HAE attacks in patients aged 2 to less than 12 years.

Uncovering the true burden of hereditary angioedema due to C1-inhibitor deficiency: A focus on the Asia-Pacific region.

Hereditary angioedema (HAE) due to C1-inhibitor deficiency or dysfunction is a rare genetic disorder that causes recurrent episodes of swelling in various parts of the body. Treatment goals of HAE aim to "normalize" life for all patients; however, lack of diagnostic facilities and limited access to effective treatment options in developing nations cause delays in diagnosis and place a significant burden on patients. In this review, we aim to highlight the burden of disease caused by C1-inhibitor HAE across the Asia-Pacific region, considering its epidemiology, morbidity and mortality, and socioeconomic and psychological impact. We also review the availability of guideline-recommended diagnostic facilities and treatments, and how patients are currently managed. Data were collected from published literature and HAE experts in the region, who provided information regarding diagnosis and management in their countries. Current practice was reviewed against international guidelines, as well as local guidelines/consensus used in Australia, Japan, and China. Suggestions are provided for improving the time to diagnosis in the region, increasing access to guideline-recommended treatments, and providing support to reduce the burden on patients and caregivers. There is an urgent need to improve HAE services and provide access to life-saving treatment in developing countries, and efforts should be made to increase awareness of guideline recommendations in high-income economies that do not currently provide long-term prophylactic treatments.

[Experiencia inicial de Lanadelumab en una paciente mexicana con angioedema hereditario tipo I].

Background: Hereditary angioedema type 1 (HAE1) is an autosomal dominant disorder, characterized by quantitative and qualitative deficiency of C1 inhibitor, excessive production of bradykinin and causing recurrent angioedema in varying degrees of severity that affects quality of life and life itself. from the patients. Lanadelumab is a human monoclonal antibody, a specific inhibitor of plasma kallikrein, approved for long-term prophylaxis of HAE1. Case report: A 59-year-old female patient, diagnosed with HAE 1 since November 1987, without therapeutic response to danazol, fresh frozen plasma, or C1 inhibitor derived from intravenous plasma, requiring 3 to 9 monthly vials of icatibant acetate due to angioedema. laryngeal, cutaneous and visceral with highly altered quality of life indices. Lanadelumab 300 mg subcutaneously every 14 days was started. At the start of treatment, the AECT1 score was 1 point; AE-Qol2: 57 points, AAS3: 32 points, being followed up at 5, 10 and 12 months. After one year of treatment, the records showed an AECT1 of 19 points; AE-Qol2: 36 points and AAS3: 5 points. The requirement for icatibant acetate has been no more than 3 vials per month. Conclusion: In accordance with the literature, lanadelumab offered a significant decrease in angioedema activity and a significantly positive impact on the pa- tient's quality of life, confirming that lanadelumab is an effective option for long-term HAE prophylaxis. .

Antecedentes: El angioedema hereditario tipo 1 (AEH1) es un trastorno autosómico dominante, caracterizado por la carencia cuantitativa y cualitativa del C1 inhibidor, producción excedida de bradicinina y causar angioedema recurrente en diversos grados de severidad que afecta la calidad de vida y la vida misma de los pacientes. Lanadelumab es un anticuerpo monoclonal humano, inhibidor específico de la calicreína plasmática, aprobado para profilaxis a largo plazo del AEH1. Reporte de caso: Paciente femenino de 59 años, con diagnóstico de AEH 1 desde noviembre de 1987, sin respuesta terapéutica a danazol, plasma fresco con- gelado ni C1 inhibidor derivado del plasma intravenoso, requerimiento de 3 a 9 ampolletas mensuales de acetato de icatibant por angioedema laríngeo, cutáneo y visceral con índices de calidad de vida sumamente alterada. Se inició lanadelumab 300 mg cada 14 días subcutánea. Al inicio del tratamiento el puntaje de AECT1 fue de 1 punto; AE-Qol2:57 puntos, AAS3: 32 puntos, realizándose un seguimiento a los 5, 10 y 12 meses. Al año de tratamiento, los registros mostraron un AECT1 de 19 puntos; AE-Qol2: 36 puntos y AAS3: 5 puntos. El requerimiento de acetato de icatibant ha sido a no más de 3 ampolletas por mes. Conclusión: En concordancia a la literatura, lanadelumab ofreció al caso, una importante disminución de la actividad del angioedema y un impacto significativa- mente positivo en la calidad de vida de la paciente, constatando que lanadelumab es una opción eficaz en la profilaxis a largo plazo del AEH.

Long-term prophylaxis for hereditary angioedema: Initial experiences with garadacimab and lanadelumab.

Background: With no approved long-term prophylaxis (LTP) for the prevention of hereditary angioedema (HAE) attacks in Hong Kong, patients rely on compassionate use programs and drug trials. Moreover, studies regarding the use and efficacy of LTP in Asia are lacking. Objectives: Our aim was to assess 2 LTP medications for HAE in Hong Kong: lanadelumab and garadacimab. Methods: A prospective study was performed. Adult patients with a diagnosis of type I or type II HAE with 1 or more expert-confirmed attacks per month were consecutively recruited. The patients had been receiving treatment for at least 6 months. Clinical data were obtained, and questionnaires were administered before treatment periodically for at least 6 months following initiation of LTP. Results: Almost one-third of the patients with HAE experienced frequent attacks and began receiving LTP (8 of the 11 received garadacimab and 3 of the 11 received lanadelumab). At baseline, the time-normalized number of HAE attacks was 2.5 plus or minus 1.3 per month. At month 6, there was an overall reduction of time-normalized number of attacks per month of -2.4 attacks per month (95% CI = -3.3 to -1.5. [P < .01]). The time-normalized number of HAE attacks at month 6 was 0.1 plus or minus 0.1 per month. More than 70% of the patients (8 of 11) were completely attack-free during the 6-month period while receiving LTP, and no patients required hospitalization. LTP improved patients' scores of the Angioedema Quality-of-Life Questionnaire (P < .001) and reduced activity impairment due to health (P = .008). Patients experienced significant improvement across all dimensions of the Treatment Satisfaction for Medication Questionnaire (54.5%-76.8% [P = .002]), and no adverse events were reported. Conclusion: The patients receiving LTP with garadacimab and lanadelumab experienced a significant reduction in number of HAE attacks and improvement in quality of life, and they were satisfied with treatment.

Successful use of lanadelumab in a patient with hereditary angioedema with normal C1 inhibitor and negative genetic testing.

We report an approximately 80% reduction in angioedema attacks with lanadelumab, a mAb targeting plasma kallikrein, in a case of hereditary angioedema with normal C1 inhibitor levels. This finding supports a central pathophysiologic role for kallikrein in hereditary angioedema with normal C1 levels and supports the need for prospective studies of lanadelumab use with this condition.

Acquired Non-histaminergic Angioedema With C1q Autoantibody and Urticaria: A Case Report.

Acquired angioedema (AAE) is a rare disease with life-threatening complications. This pathology has classically been associated with medication use and B cell lymphoproliferative disorders. In this report, we describe a 61-year-old man with a six-year history of angioedema, unrelated to any known triggers or malignancy. Extensive workup has led to a diagnosis of idiopathic nonhistaminergic AAE with normal C1 inhibitor. The patient is currently being treated with lanadelumab, which has resolved the patient's symptoms. This case provides insight into the onset, exploration, treatment, and outcomes of an extremely rare disease process.

Efficacy and safety of lanadelumab in Japanese patients with hereditary angioedema: A phase 3 multicenter, open-label study.

The safety and efficacy of lanadelumab for the prevention of hereditary angioedema (HAE) attacks have not been studied in Japanese patients. We report outcomes from a phase 3, multicenter, open-label study (NCT04180163) of lanadelumab in Japanese patients with HAE. Japanese patients with HAE aged ≥12 years with ≥1 investigator-confirmed HAE attack during the 4-week run-in baseline period were enrolled into the study and received lanadelumab 300 mg every 2 weeks subcutaneously for 52 weeks. Dosing could be reduced to 300 mg every 4 weeks during the second 26-week treatment period if patients had well-controlled symptoms (e.g., attack-free) for 6 months. The primary efficacy endpoint was no investigator-confirmed HAE attacks (attack-free status) during days 0-182. Other outcomes included the rate of investigator-confirmed HAE attacks per month (28 days) and lanadelumab safety. Twelve patients (mean ± SD age 41.9 ± 12.4 years) were enrolled. During the first 26 weeks (days 0-182), five (41.7%) patients were attack-free. The mean ± SD HAE attack rate per month decreased by 74.0%, from 3.8 ± 2.4 during baseline to 1.2 ± 2.6 during the overall 52-week treatment period. There were no deaths or discontinuations due to treatment-emergent adverse events (TEAEs), no severe or serious TEAEs related to lanadelumab, and no positive anti-drug antibody results. The most frequent TEAEs were injection-site reactions (37 events in six patients). Most of the injection-site reaction adverse events were mild in severity. Results of this study support the findings from two global phase 3 studies for lanadelumab use as prophylactic therapy in Japanese patients with HAE.

Network meta-analysis for indirect comparison of lanadelumab and berotralstat for the treatment of hereditary angioedema.

Aim: With no head-to-head studies comparing the effectiveness of lanadelumab and berotralstat for prevention of hereditary angioedema (HAE) attacks, this network meta-analysis (NMA) aimed to indirectly compare the effectiveness of these treatments. Materials & methods: The NMA, using the published data from Phase III trials, was performed using a frequentist weighted regression-based approach following Rücker et al. Efficacy outcomes of interest were HAE attack rate per 28 days and ≥90% reduction in monthly HAE attacks. Results & conclusion: In this NMA, lanadelumab 300 mg administered every 2 weeks or every 4 weeks was associated with statistically significantly higher effectiveness versus berotralstat 150 mg once daily (q.d.) or 110 mg q.d. for both efficacy outcomes assessed.

Safety of medications for hereditary angioedema during pregnancy and lactation.

INTRODUCTION: Hereditary Angioedema (HAE) attacks show an increased frequency and severity for pregnant and lactating females secondary to the hormonal changes. The diagnosis and management of HAE in pregnant and lactating females pose a challenge for physicians due to the rarity of the disease and the paucity of the data for specific management. AREAS COVERED: In this manuscript, we discuss the diagnosis and special presentation of HAE types 1 and 2 in pregnant and lactating females, including acute management, short-term prophylaxis, long-term prophylaxis, and drugs that should be avoided. Relevant publications were found through key word search of papers indexed in both Google Scholar and PubMed on 1 July 2022. EXPERT OPINION: Treatment of HAE in the past has been mainly provided by experts; however, with more medications and an increasing number of patients, knowledge of how to care for HAE patients during pregnancy and lactation is important to review. Despite approval of additional medications in many countries, plasma-derived C1-inhibitor remains the drug of first choice for treatment in this unique population. Additional research is needed to increase safe access to other therapy options. We hope that future clinical studies, registries, and databases will shed additional light on this subject.

Therapeutic monoclonal antibodies with a focus on hereditary angioedema.

Monoclonal antibodies (mAbs) have been shown to be effective and generally safe across a continually expanding list of therapeutic areas. We describe the advantages and limitations of mAbs as a therapeutic option compared with small molecules. Specifically, we discuss a novel mAb in the treatment of hereditary angioedema (HAE), a rare and potentially life-threatening condition characterized by recurrent unpredictable swelling attacks. HAE is mediated by dysregulation of plasma kallikrein activity leading to overproduction of bradykinin. Current prophylactic treatment for HAE includes androgens or replacement of the endogenous plasma kallikrein inhibitor, C1 inhibitor. However, there remains an unmet need for an effective, less burdensome treatment option. Lanadelumab is a fully human mAb targeting plasma kallikrein. Results from clinical trials, including a pivotal Phase 3 study and its ensuing open-label extension study, demonstrated that lanadelumab is associated with few treatment-related adverse events and reduced the rate of HAE attacks. This novel treatment option has the potential to significantly improve the lives of patients with HAE.

Safety Aspects and Rational Use of Lanadelumab Injections in the Treatment of Hereditary Angioedema (HAE): Clinical Insights.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of skin/mucosal swelling, and/or attacks of severe abdominal pain when it affects the gastrointestinal tract. The disease might be unexpectedly fatal when the upper airways are compromised. HAE clinical presentation, disease course and prognosis are associated with significant disease burden and severely impaired quality of life. Lanadelumab is a breakthrough therapy for the prevention of attacks in HAE type 1 and 2 patients. This revolutionary approach to administer a single subcutaneous injection (once every two to four weeks) and achieve complete disease control has dramatically improved patient care resulting in significant change in the life of affected families. Current data support the drug's tolerability in adult and adolescent patients without notable safety concerns in both clinical research and real-world settings. Rational use of prophylactic treatments of HAE searches for a socio-economic balance, taking into account the life-long course of the disease, the public health funds who pay the monetary price, and the patients who might need to receive the therapy for a period longer than investigated during the development program. In this review, we address the current evidence on lanadelumab's tolerability, highlighting aspects of the drug's rationale use in clinical practice. Further studies need to investigate whether this therapy might be appropriate in other forms of angioedema, such as idiopathic primary angioedema and HAE with normal C1 inhibitor. Future efforts must focus to improve modern drugs' accessibility in more countries. Although modern prophylactic options lessen the risk of fatal laryngeal attacks, patients must be equipped with reliable on-demand therapies and be trained how to use them as such a risk cannot be fully diminished with potentially life-threatening attacks occurring even in subjects with successful and stable long-term prophylaxis. Notwithstanding, further studies are needed to identify early responders from non-responders and develop therapies for the latter.

Effectiveness and safety of lanadelumab in ethnic and racial minority subgroups of patients with hereditary angioedema: results from phase 3 studies.

BACKGROUND: The COVID-19 pandemic has highlighted disparities in healthcare, particularly in the United States, even though disparities have existed since the organization of the modern healthcare system. Recruitment of patients from racial and ethnic minority groups is often minimal in phase 3 clinical trials, and is further exacerbated in the case of trials for rare diseases such as hereditary angioedema (HAE). This can lead to a gap in the understanding of minority patients' experiences with these diseases and their response to potential treatment options. METHODS: We reviewed data from phase 3 double-blind (HELP) and open-label extension (HELP OLE) trials of lanadelumab, a monoclonal antibody developed for long-term prophylaxis against attacks of HAE. Efficacy (attack rate reduction) and safety (adverse events) results from White patients were compared descriptively to those from Hispanic/Latino patients, Black/African Americans, and other minority Americans. RESULTS: Not surprisingly, few minorities were recruited across both studies: 9.5% Black, 2.4% Asian, and 7.1% Hispanic/Latino versus 88.1% White and 91.7% non-Hispanic/non-Latino received lanadelumab in HELP, and 4.7% Black, 0.9% Asian, 0.9% other, and 6.1% Hispanic/Latino versus 93.4% White and 93.4% non-Hispanic/non-Latino were enrolled in HELP OLE. Although these studies were conducted in the United States, Canada, Europe, and Jordan, all minorities were from the United States. Despite the number of minority patients being far less than expected for the population, there was no evidence that either efficacy or adverse event profiles differed between ethnic or racial groups. CONCLUSIONS: The HELP and HELP OLE studies described herein recruited far fewer minorities than would be ideal to represent these populations. However, evidence suggests that the effectiveness and tolerance of lanadelumab are similar between the groups. Nonetheless, the disparity in recruitment into research for minorities has significant room for improvement. Trial registration NCT02586805, registered 26 October 2015, https://clinicaltrials.gov/ct2/show/record/NCT02586805 . NCT02741596, registered 18 April 2016, https://clinicaltrials.gov/ct2/show/NCT02741596 .