Real-World Outcomes and Healthcare Utilization of Lanadelumab in Spain: Insights from First Cohort of Difficult-to-Treat Hereditary Angioedema Cases

Abstract

Background/Objectives: Hereditary angioedema (HAE) is a rare genetic condition marked by recurring episodes of intense swelling that affect the skin, gastrointestinal system, and airways. Lanadelumab, a monoclonal antibody that inhibits plasma kallikrein, is approved for long-term prophylaxis (LTP) in HAE patients, and has shown substantial efficacy in reducing disease symptoms. This single-center, retrospective study analyzed the real-world impact of lanadelumab on healthcare resource utilization, angioedema episode frequency, and quality of life (QoL) among adult HAE patients treated at the allergy department of Hospital Universitario de Canarias, Tenerife, Spain. Methods: This study included patients with a confirmed diagnosis of bradykinin-mediated HAE type 1 who were receiving lanadelumab 300 mg subcutaneously every two weeks, meeting specific inclusion criteria. A retrospective review of medical records from March 2021 to June 2024 assessed clinical outcomes under lanadelumab therapy, compared to prior clinical status. Key metrics included angioedema attack frequency, use of on-demand icatibant treatment, hospital visits, and QoL using the HAE-QoL questionnaire, alongside any adverse reactions associated with lanadelumab. Results: The investigation revealed a 75.3% reduction in hospital visits and a 94.1% decrease in angioedema episodes among HAE patients. Additionally, use of on-demand rescue medication (icatibant) was reduced by 61% (p < 0.05), while quality of life (QoL) scores improved from 62.2 to 99.5, with no significant adverse effects reported. Conclusions: Lanadelumab significantly reduced healthcare resource use and angioedema episodes, with marked improvements in quality of life. The reduced need for on-demand medication and hospital visits highlights lanadelumab’s value as an effective long-term prophylactic treatment with minimal adverse effects for HAE patients in real-world settings.

1. Introduction

Hereditary angioedema (HAE) is a rare (1.5:100,000), life-threatening, autosomal dominant disorder characterized by unpredictable and recurrent episodic swelling, most commonly involving the skin, gastrointestinal tract, and/or upper airways [1,2]. This study will adopt the DANCE nomenclature for classification purposes [3]. In HAE due to C1-inhibitor (C1-INH) deficiency, two main forms are recognized: HAE type I, which is characterized by quantitatively low levels of C1-INH, and makes up 85% of all cases, and HAE type II, which involves a normal C1-INH antigenic level but impaired functional activity, and makes up approximately 15% of cases [4]. C1INH regulates various interrelated proteolytic cascades, including the contact, fibrinolytic, coagulation, and complement systems. C1INH inhibits proteases across various systems, including the contact (kallikrein), fibrinolytic (plasmin, fibrinogen, fibrin), coagulation (Factors XIIa, XIa), and complement cascades, specifically the classical (C1r, C1s) and lectin pathways (MASP-1, MASP-2) [5].

Bradykinin, the primary mediator of HAE, is a potent vasodilator generated in the contact system. It is released from its precursor, high-molecular-weight kininogen, following the activation of prekallikrein into kallikrein by Factor XII (FXIIa). C1 inhibitor serves as the main regulator primary of contact factors, inhibiting 93% of FXIIa and 52% of prekallikrein in plasma [6].

Clinical management of HAE includes long-term prophylaxis (LTP) to reduce angioedema episodes, on-demand treatment (ODT) to reduce the duration of acute episodes, and short-term prophylaxis (STP) for situations that may trigger an outbreak. Lanadelumab, a fully humanized monoclonal antibody that specifically inhibits plasma kallikrein and reduces bradykinin production, was approved for LTP of HAE in Spain in April 2021. The recommended dosage for prophylaxis is 300 mg, administered subcutaneously (SC) every 2 weeks (q2W), while an alternative dosing interval of 300 mg SC q4W may be effective for patients who have been well controlled (attack-free) for more than 6 months [7].

In Spain, lanadelumab is an additional therapeutic option for managing HAE attacks. It is funded for patients aged 12 and older with HAE types I and II and is specifically approved for the routine prevention of recurrent attacks [7]. It is particularly recommended for patients with high disease activity when ODT does not provide sufficient control. Evaluations consider the frequency and severity of attacks, quality of life impact, and overall disease burden [8]. The main goals of LTP with lanadelumab are to reduce attack frequency and severity and improve quality of life, though there is no specific attack frequency threshold for starting treatment. Due to its high cost, local healthcare providers use budgetary and hospital-specific protocols to manage access, ensuring efficient and safe use for patients with significant clinical needs.

The primary aim of this study was to investigate potential cost reductions for payers and the healthcare system associated with LTP of HAE using lanadelumab. To achieve this, we evaluated the impact of lanadelumab treatment on hospital consultations, including medical, nursing, pharmacy, and emergency visits, as well as consultations via WhatsApp and phone. Secondary objectives included analyzing angioedema episode frequency, the need for ODT with icatibant, and STP before high-risk medical procedures. Additionally, this study compared HAE-QoL quality of life questionnaire results and monitored any adverse reactions related to lanadelumab use.

2. Materials and Methods

2.1. Subjects and Study Variables

As of 2023–2024, the population of Tenerife, Spain, exceeds 950,000 residents [9]. Approximately half of these individuals (498,208 healthcare users) are served by our institution, which covers the northern health district. This study was a single-center, observational, retrospective analysis that included only participants fulfilling specific inclusion criteria: patients with a bradykinin-mediated HAE type 1 diagnosis confirmed by a trained allergist who were receiving treatment with lanadelumab 300 mg SC q2W. Pregnant and breastfeeding women were excluded from this study. Approval was obtained from the local Ethical Committee of our institution (code number CHU-2024-94), and informed consent was provided by all participants, with parents or guardians signing for those under 18 years of age.

Data were retrospectively gathered from patients’ clinical records between March 2021 and June 2024 to assess their clinical progression under lanadelumab therapy compared to their previous clinical status. The analysis focused on the following metrics: clinical outcomes (frequency and detailed descriptions of angioedema attacks, the need for on-demand treatment with icatibant, and short-term prophylaxis before high-risk medical procedures), healthcare resource utilization (number of in-person hospital visits, including medical, nursing, pharmacy, and emergency room consultations, as well as remote consultations via WhatsApp and/or phone), QoL using validated tools (HAE-QoL questionnaire), and monitoring of any adverse reactions potentially related to lanadelumab use. The study flow is illustrated in Figure 1.

2.2. Statistical Analysis

The median and interquartile range (IQR) were utilized to assess age and post-lanadelumab follow-up periods. ANOVA was employed for comparison involving more than two groups, with a p-value of less than 0.05 considered statistically significant. All statistical analyses were conducted using GraphPad Prism version 10.0.0 for Windows, GraphPad software, La Jolla, CA, USA.

3. Results

3.1. Characteristics of Investigated Patients

Currently, our institution is actively monitoring 21 patients with distinct types of bradykinin-mediated angioedema, excluding those cases caused by angiotensin-converting enzyme (ACE) inhibitors. Among these patients are the following cases:

• HAE type I: 10 patients (47.6%) with a fully confirmed diagnosis;
• HAE type II: eight patients (38%);
• HAE-FXII: two patients (9.5%);
• Acquired angioedema (AEA): one patient with C1q deficiency.

Of these 21 patients, the following applies:

• In total, 14 (66.6%) did not require LTP;
• Two males (9.5%) with HAE type I and type II underwent LTP with danazol;
• Four females (19%) were receiving LTP with lanadelumab.

The remaining patient with AEA underwent LTP with amchafibrin. Three infants underwent evaluation for angioedema but were not included in this study. All patients had icatibant available as ODT.

A total of four Caucasian female patients, all diagnosed with HAE type I, were finally enrolled in this study. Their median age was 50.5 years (interquartile range [IQR] 13.5), with ages ranging from 39 to 78 years. Among these four patients receiving LTP with lanadelumab, three transitioned from plasma-derived C1-esterase inhibitor (PdC1-INH) treatment, while the fourth switched from danazol, which was administered intravenously twice a week due to lack of efficacy. The first patient had been on danazol since her twenties but switched to PdC1-INH because of high blood pressure. The second patient was referred from internal medicine after a biopsy confirmed androgenic alopecia; she had independently increased her danazol dosage to 600 mg daily and started PdC1-INH therapy in 2016, initially responding well. The third patient began PdC1-INH therapy during her first pregnancy, but her condition remained poorly controlled. The fourth patient developed hypertension after receiving a low dose of danazol (200 mg every 48 h) since adolescence and refused parenteral administration due to a fear of needles, prompting the decision to try berotralstat. However, substituting danazol for berotralstat led to increased angioedema attacks, resulting in a clinical decision to continue berotralstat while gradually tapering danazol. This strategy failed to improve her condition, ultimately leading to a switch to lanadelumab. Currently, her husband administers the doses of lanadelumab after being trained by the nursing team, as she refused self-administration of all doses of PdC1-INH, which were given at the hospital.

The four investigated patients began LTP with lanadelumab between March 2021 and February 2024, with follow-up periods ranging from 5 to 40 months and a median duration of 23 months (IQR 16.25), resulting in a cumulative follow-up time of 91 months across all patients. All patients started treatment with a dosage of 300 mg administered subcutaneously every two weeks (SC q2W). After the first six months, the dosing interval was adjusted for two patients (50%) to 300 mg SC every four weeks (q4W). One patient initially required a more frequent adjustment, receiving lanadelumab 300 mg SC every ten days due to episodes occurring shortly before the two-week interval; however, this patient eventually returned to the standard two-week dosing. Throughout this study, all patients had icatibant available for ODT. The relevant demographic and clinical characteristics are detailed in

Table 1. General demographic and clinical characteristics –number and locations of acute attacks- of each patient, before and after lanadelumab long-term prophylaxis.

	Patient 1		Patient 2		Patient 3		Patient 4
Gender/age (y)	♀/78		♀/53		♀/39		♀/48
HAE type	1		1		1		1
Comorbidities	Non-Hodgkin lymphoma HBP Nodular thyroid hyperplasia AMI Depression		Androgenic alopecia secondary to danazol Depression		Premature birth		HBP
Age at diagnosis of HAE	27 y		2 y		27 y		18 y
LTP prior to switching to lanadeluma	Pd1-inh i.v. 2x/week (Since 2017)		Pd1-inh i.v. 2x/week (Since 2019)		Pd1-inh i.v. 2x/week (Since 2022)		Danazol (Since 2002) + Berotralstat (since Oct 2023)
Lanadelumab started	March 2021		March 2022		January 2023		February 2024
Number and location of acute attacks in previous year and months after switch to lanadelumab
	Before	After	Before	After	Before	After	Before	After
Extremities	7	0	3	0	27		4	0
Abdominal	5	Two attacks in first 6 months after switch	8	Four attacks in first 12 months after switch	17	Five attacks in first 3 months after switch	3
Genital	0	0	0	0	5		3	0
Laryngeal	0	0	0	0	1
Others	0	0	0	0	1		1	0
Attack-free months since last HAE attack, post lanadelumab therapy	33 months		16 months		14 months		5 months

HAE: Hereditary angioedema; AMI: acute myocardial infarction; HBP: high blood pressure.

.

The pedigrees of families with various types of angioedema currently monitored at our institution are presented in

Table 2. Pedigrees of families with angioedema currently being monitored at our institution. Red indicates patients on long-term prophylaxis (LTP) with lanadelumab. “X” represents a patient’s fatality.

Pedigrees of Families with Various Types of Angioedema
Family 1: One patient with HAE type II on danazol for LTP.
Family 2: In this family, a baby is awaiting diagnosis.
Family 3: This family is from the United Kingdom and has minimal symptoms.
Family 4
Family 5
Family 6: One of the sisters overcame leukemia, during which she required C1-INH therapy; currently, she does not require LTP.
Family 7: This family includes patients number 1 and 2 from Table 1.
Family 8: In this family, the patient marked in red is patient number 3 from Table 1, and her brother is on LTP with danazol.
Family 9: This family includes patient number 4 from Table 1.
Family 10: Two members of this family live in Galicia, Spain; only one sister lives in our Autonomous Community (Canary Islands, Spain).
Family 11: The patient’s two daughters have not been studied; they currently live in Germany.
Family 12: We have known this patient since 2000. She has never associated any medical process associated with C1q consumption. She is maintained on amchafibrin for LTP.

, illustrating the inheritance patterns and clinical features of affected individuals.

3.2. Roles of Medical, Nursing, and Hospital Pharmacy Teams in the Management and Control of HAE in Patients Receiving Biological Therapies

In our hospital, the management of biological therapies—often costly—requires close monitoring by medical professionals, nursing staff, and pharmacy teams. While this oversight may seem redundant, it is essential given the significant expenses and potential complexities associated with these therapies (

Table 3. Roles of medical, nursing, and pharmacy teams in biological therapy management.

Disciplines	Roles
Medical Care
Monitoring of Effectiveness and Safety	Conduct regular assessments to measure treatment response, adjusting doses or changing therapies if necessary; monitor side effects or adverse reactions, and manage urgent episodes.
Coordination with Multidisciplinary Teams	Collaborate with pharmacy, nursing, and other healthcare professionals to implement administration, monitoring, and comprehensive patient management protocols.
Patient Education and Guidance	Inform patients of the benefits, risks, and possible side effects of biological therapy, ensuring they fully understand their treatment.
Management of Adverse Effects and Complications	Develop intervention strategies to address adverse events or complications related to therapy, including treatment adjustments and emergency care. Report adverse effects to pharmacovigilance.
Ongoing Research and Continuing Education	Participate in clinical studies, review the scientific literature, and update knowledge on new therapies and advancements in biological treatments.
Cost-effectiveness Evaluation	Assess the cost–benefit relationship of biological therapies, especially in complex diseases, aiding in decision-making about treatment sustainability.
Clinical Documentation and Reporting	Maintain a detailed record of patient progress, treatment response, and any relevant incidents, ensuring a complete electronic medical record is kept.
Nursing Care
Patient and Family Education	Explain the purpose of biological therapy, administration methods, and possible side effects, promoting self-care and addressing questions.
Safe Medication Administration	Prepare and administer biological therapies according to strict protocols, ensuring proper administration techniques (subcutaneous, intravenous) and minimizing errors.
Monitoring of Adverse Effects	Observe and record signs of adverse reactions or undesirable events after administration, responding rapidly in emergencies and notifying the healthcare team.
Adherence Tracking and Support	Ensure that patients follow the prescribed treatment, identifying barriers to adherence and providing support to ensure continuity of treatment.
Self-care and Self-administration Support	Train patients who must self-administer medication at home, teaching safe techniques and supervising their ability to perform the administration correctly.
Appointment Coordination and Scheduled Administration	Manage dosing schedules according to the treatment plan, ensuring patients receive therapies at the appropriate time.
Documentation and Reporting	Record all relevant information on administration, treatment response, and any incidents, maintaining open communication with the healthcare team. Nursing maintains its own electronic nursing record.
Emotional and Psychological Support	Provide emotional support, helping patients manage anxiety or concerns related to their treatment, promoting better adaptation to therapy.
Hospital Pharmacy Care
Personalized Dispensing and Patient Education	Provide detailed information on the use and handling of biological therapies, instructing patients on administration and potential side effects.
Pharmacotherapeutic Monitoring	Monitor treatment response, side effects, and make adjustments according to the patient’s progress and clinical outcomes.
Pharmacovigilance	Identify and record adverse reactions and potential interactions, collaborating on adverse event reporting to pharmacovigilance systems.
Resource Optimization	Manage inventory and ensure availability of biological medications, considering their high cost and the need for special storage conditions.
Treatment Adherence Support	Supervise patient compliance with the therapeutic regimen, implementing strategies to improve adherence in long-term treatments.
Participation in Committees and Decision-making	Collaborate in multidisciplinary committees to evaluate the inclusion of new biological therapies and establish evidence-based usage protocols.
Cost and Efficiency Consulting	Analyze the cost–benefit relationship of biological therapies, supporting decisions on the funding and prioritization of treatments for patients with specific clinical needs.

).

3.3. Healthcare Resource Utilization

3.3.1. Allergy Department (Allergist and Nursing) Consultations

In the year prior to switching to lanadelumab for LTP, the four patients in this investigation collectively made 343 visits to the allergy department, consisting of 119 medical consultations and 224 nursing consultations. This equated to an average of 7.1 visits per month per patient, with 2.4 medical visits and 4.6 nursing visits each month. During the cumulative 91 months of follow-up after starting LTP with lanadelumab, these patients made a total of 135 visits to the allergy department—41 medical consultations and 94 nursing consultations—averaging 1.4 visits per month per patient (0.4 medical visits and 1 nursing visit). Additionally, two patients transitioned to telephone medical consultations, with 4% of all medical consultations after starting lanadelumab conducted by phone.

When comparing hospital visits before and during the last 12 months of follow-up for the three of four patients who had been on lanadelumab for over a year, there was a significant reduction in both medical and nursing consultations. Prior to starting lanadelumab, the average number of medical visits was 35.33 per year. In the last 12 months of follow-up, the mean dropped to 1.66, reflecting a significant decrease of 33.67 visits (t = 2.876, p = 0.041). Similarly, the mean number of nursing visits decreased from 74.67 in the year before treatment to 7.67 in the last year, representing a reduction of 67.00 visits with strong statistical significance (t = 5.723, p = 0.0003) as shown in Figure 2.

3.3.2. Hospital Pharmacy Visits

In the year before switching to LTP with lanadelumab, all four patients made a total of 172 visits to the hospital pharmacy. Over the 91 months of follow-up after starting lanadelumab, this number dropped to 107 visits, reducing the average from 3.5 visits per month per patient to 1.1 visits. For the three patients who had been on lanadelumab for more than a year, the mean number of pharmacy visits was 54.00 in the year prior to treatment, compared to 10.67 in the last year of follow-up. This decrease of 43.33 visits is statistically significant (t = 3.701, p = 0.0091) (Figure 2).

3.3.3. Trends in Hospital Visits After LTP with Lanadelumab

An early response to lanadelumab therapy was observed when comparing hospital visits in the year prior to treatment with visits in the first 6 and 12 months afterward. This analysis, conducted for the three patients who had been on lanadelumab for more than six months, showed statistically significant reductions across all areas.

• Medical visits decreased significantly, with a mean reduction to 30.00 visits at 6 months (t = 4.354, p = 0.0096) and 26.33 visits at 12 months (t = 3.822, p = 0.017).
• Nursing visits followed a similar pattern, with a mean reduction of 64.67 visits at 6 months (t = 5.052, p = 0.0047) and 57.67 visits at 12 months (t = 4.5054, p = 0.0081).
• Hospital pharmacy visits also declined, with a mean reduction of 43.67 visits at 6 months (t = 4.017, p = 0.0124) and 35.67 visits at 12 months (t = 3.281, p = 0.0295).

These results confirmed significant improvements across all measured areas within the first year of lanadelumab treatment (Figure 3).

3.3.4. Emergency Department Visits

Two of the patients utilized private insurance for their emergency visits exclusively, so data for these visits were not available in the hospital’s EMR. For the remaining two patients, the average number of emergency visits in the year before switching to lanadelumab was seven episodes, or 0.30 visits per patient per month. After initiating lanadelumab, none of the patients required emergency department visits. However, due to the limited data, statistical significance could not be demonstrated.

3.3.5. WhatsApp Consultations

Most of the patients included in this study (75%) utilized WhatsApp. In the year prior to switching to lanadelumab, the mean number of WhatsApp messages for these patients was 6.6, averaging 0.55 messages per month per patient. After starting lanadelumab, this average decreased to 0.45 messages per month per patient. However, this trend did not reach statistical significance.

3.4. Number of Angioedema Episodes and Use of ODT with Icatibant

As noted, all four patients had immediate access to icatibant for ODT. In the year prior to switching to lanadelumab, the average use of icatibant was 1.3 doses per patient per month, totaling 67 icatibant units. After transitioning to lanadelumab, this decreased to 0.2 doses per patient per month, totaling 26 units, representing a statistically significant (p < 0.05) reduction of 61% in the use of ODT icatibant (

Table 4. On-demand treatment (ODT) with icatibant: individual units before and after starting lanadelumab. The use of icatibant units as an ODT was analyzed across 96 total months prior to initiating lanadelumab therapy and 91 total months following the switch to lanadelumab.

Use of ODT	Before (n)	After (n)	Change (%)
Patient #1	17 units in 12 mo.	4 units in 40 mo.	−76
Patient #2	11 units in 12 mo.	6 units in 28 mo.	−45
Patient #3	34 units in 12 mo.	16 units in 18 mo.	−53
Patient #4	5 units in 12 mo.	0 units in 5 mo.	−100
TOTAL	67	26	−61

).

The mean number of icatibant units used per patient in the year prior to starting lanadelumab was 16.75, whereas in the months following the switch, the mean decreased to 6.50 units. This reduction in icatibant use was statistically significant (p = 0.049), as shown in Figure 4.

All patients reported significant reductions in the frequency of acute attacks. Prior to switching to lanadelumab, the four patients, who had been on long-term prophylaxis with plasma-derived C1-esterase inhibitor (PdC1-INH) for three individuals, and berotralstat plus danazol for the fourth, experienced a mean of 21.25 episodes of angioedema in the year before the transition (standard deviation 19.84), averaging 1.77 episodes per month per patient. In contrast, following the switch to lanadelumab, the mean number of episodes decreased significantly to 3.0 in the year after the switch (standard deviation 2.58), resulting in an average of only 0.12 episodes of angioedema per month per patient (Figure 5).

There appears to be a trend toward improvement in the use of lanadelumab with longer follow-up times, as HAE attacks are concentrated in the year following the initiation of LTP. Currently, all four patients receiving lanadelumab are attack-free, averaging 17 months without further angioedema episodes, with individual durations ranging from 5 to 33 months. Notably, all angioedema episodes that occurred after starting lanadelumab were abdominal in nature and were managed at home with icatibant, thereby eliminating the need for emergency visits. Furthermore, only one patient experienced a life-threatening episode of laryngeal edema in the year prior to starting lanadelumab, and no severe episodes have occurred since (Table 1).

3.5. Improved Disease Control as Measured by the HAE-QoL (Hereditary Angioedema Quality of Life) Questionnaire

The validated HAE-QoL questionnaire evaluates QoL in hereditary angioedema (HAE) patients, with scores ranging from 25 to 135; higher scores indicate better quality of life. The average score before starting lanadelumab was 62.2 (SD: 16.15), with a range of 44 to 81. After the switch to lanadelumab, the mean score was significantly increased to 99.50 (SD: 20.07), ranging from 73 to 121 (Figure 6).

3.6. Adverse Reactions Related to the Use of Lanadelumab

None of the patients (0%) reported adverse reactions to lanadelumab throughout the study period. They unanimously found it easier to administer compared to icatibant, which they described as “more painful”. Furthermore, one patient with a fear of needles depended on her partner to administer both lanadelumab and icatibant.

3.7. Use of Short-Term Prophylaxis After Initiation of Lanadelumab

None of four the patients (0%) required STP to prevent potential angioedema attacks during concomitant medical procedures. Collectively, they underwent two cycles of chemotherapy for non-Hodgkin lymphoma, one colonoscopy with polyp removal, and three dental procedures, which included fillings and cleanings.

4. Discussion

Real-world data on lanadelumab treatment are scarce, primarily emphasizing efficacy, safety, and QoL in existing studies [10,11,12,13]. Our research stands out as the first retrospective analysis of HAE patients receiving lanadelumab in real-world settings, with a specific focus on healthcare utilization. Furthermore, it represents the first Spanish series to present real-world data on this treatment.

The number of healthcare visits for HAE patients varies based on disease burden, personal circumstances, and individual needs. Even patients with similar clinical profiles can demonstrate differing requirements for healthcare utilization and access. In the context of rare diseases, the limited availability of published real-world data creates a knowledge gap for both healthcare providers and managers.

Analyzing the cost-effectiveness of lanadelumab therapy, including its administration frequency and potential reductions in healthcare utilization, is essential for understanding its overall financial impact on both patients and healthcare systems [14]. Additionally, understanding the balance between drug costs and the economic benefits derived from fewer hospital visits and improved quality of life is essential for making informed treatment decisions. Furthermore, the elevated cost of lanadelumab in Spain [15] for patients on LTP raises the need to evaluate whether this expense is balanced by a reduction in hospital visits, the use of specific rescue medication, fewer angioedema episodes, and ultimately an improvement in their overall QoL.

Our experience demonstrated a substantial reduction in hospital visits following the initiation of LTP with lanadelumab, including decreases in both medical and nursing visits to the allergy department, as well as hospital pharmacy visits. While the reduction in emergency room visits did not reach statistical significance, there were trends indicating improvement. The four patients in this study made a total of 515 hospital visits (343 to the allergy department and 172 to the hospital pharmacy) during the 48 months prior to starting lanadelumab LTP. In contrast, they accumulated only 242 visits (135 to the allergy department and 107 to the pharmacy) over 91 months of follow-up after beginning treatment. On average, hospital visits per patient dropped from 10.2 visits per month to 2.6 visits per month, marking a significant 75.27% reduction. Additionally, although the decrease in WhatsApp consultations was not statistically significant, the introduction of telephone consultations, which rose to 4%, suggests increased patient autonomy and reduced hospital dependency.

Despite several limitations that should be addressed, including the retrospective nature of the data and the relatively small sample size of four difficult-to-treat HAE patients, our study provides valuable insights into the real-world management of complex cases. These patients were highly symptomatic and required long-term intravenous prophylaxis prior to switching to lanadelumab. Their proximity to the hospital may have contributed to a higher frequency of hospital visits, but the significant reductions in healthcare utilization following lanadelumab therapy suggest a meaningful clinical benefit. While the small sample size warrants cautious interpretation, the statistically significant results point to potential improvements in both patient outcomes and healthcare resource utilization. Treatment with lanadelumab has significantly improved the quality of life for HAE patients, consistent with findings from other studies [16,17,18,19,20], including both the randomized HELP study and its open-label extension (OLE) [21,22]. Moreover, it has shown superior efficacy in preventing attacks compared to other long-term prophylaxis options, including pdC1-INH IV [23], danazol [24], and berotralstat [25]. In addition, the convenience of SC administration, whether monthly or bi-weekly, may further enhance patient autonomy and therapy adherence. Remarkably, in our cohort, the number of HAE attacks dropped by 94.1%, from an average of 1.7 episodes per month per patient before starting lanadelumab to 0.1 episodes during follow-up. Similarly, the need for on-demand treatment (ODT) decreased by 84.6%, from 1.3 doses per patient per month before lanadelumab to 0.2 doses afterward. As of the latest follow-up, the four monitored patients (100%) have been attack-free for an average of 17 months, ranging from 5 to 33 months, and have undergone various medical procedures without requiring STP.

5. Conclusions

The present investigation demonstrates that lanadelumab, in LTP, significantly reduces healthcare resource utilization and the frequency of angioedema episodes in selected difficult-to-treat HAE patients. Future studies with larger cohorts and longer follow-ups are needed to confirm these results and evaluate the long-term cost-effectiveness of lanadelumab in managing HAE. Nonetheless, our experience suggests that lanadelumab is a valuable and effective option for difficult-to-treat HAE patients, offering clinical benefits alongside potential reductions in healthcare costs. These findings highlight the potential of lanadelumab in managing complex HAE cases and emphasize the need for further research to validate these trends. Sharing clinical experiences remains essential, particularly in rare diseases like HAE, where real-world data on expensive treatments in public healthcare systems is limited.