The humanistic burden of hereditary angioedema: Results from the Burden of Illness Study in Europe Teresa Caballero, M.D., Ph.D.,1 Emel Aygo¨ren-Pu¨rsu¨n, M.D.,2 Anette Bygum, M.D.,3 Kathleen Beusterien, M.P.H.,4 Emily Hautamaki, M.P.H.,4 Zlatko Sisic, M.D., M.B.A.,5 Suzanne Wait, Ph.D.,6 and Henrik B. Boysen7
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ABSTRACT Hereditary angioedema (HAE) is a rare but potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The broad range of consequences of HAE on patients’ lives is not well understood. The study objective was to comprehensively characterize the burden of illness and impact of HAE types I and II from the patient perspective. The HAE Burden of Illness Study in Europe was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective via a one-time survey, which included items on clinical characteristics and physical and emotional impacts. One hundred eighty-six patients participated; 59% reported having an attack at least once a month, 67% reported moderate-to-severe pain during their last attack, and 74% reported moderate-to-severe swelling. The most common sites of the last attack were the abdomen and extremities; 24% experienced an attack in more than one site. The impact of HAE on daily activities was high during attacks and did not vary significantly by body site affected; patients also reported that HAE impacted their daily activities between attacks. Patients reported substantial anxiety about future attacks, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial impairment physically and emotionally both during and between attacks. A better understanding of these effects may help in the clinical management of HAE patients. (Allergy Asthma Proc 35:47–53, 2014; doi: 10.2500/aap.2013.34.3685)
H
1
From the Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz), Biomedical Research Network on Rare Diseases U754 (CIBERER), University Hospital La Paz, Madrid, Spain, 2Pediatric Clinic, University Hospital Frankfurt, Goethe University, Frankfurt, Germany, 3HAE Centre Denmark, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark, 4Oxford Outcomes, Inc., Bethesda, Maryland, 5ViroPharma, Chatsworth House, Maidenhead, United Kingdom, 6SHW Health, Ltd., London, United Kingdom, and 7HAEi–International Patient Organization for C1 Inhibitor Deficiencies, Hasselager, Denmark Presented at the European Academy of Allergy and Clinical Immunology Congress, June 16–20, 2012, Geneva, Switzerland, and the European Society for Immunodeficiencies Biennial Meeting, October 3–6, 2012, Florence, Italy Funded by by ViroPharma SPRL-BVBA T Caballero, received sponsorship for educational purposes, has been paid for providing consultancy services, or has taken part in clinical trials sponsored by Jerini AG/Shire, CSL-Behring, Pharming NV, Sobi, and ViroPharma. E Aygo¨en-Pu¨rsu¨n, has received sponsorship for educational purposes and has provided consultancy services or has participated in clinical trials sponsored by CSL-Behring, Jerini AG/Shire, Sobi, and ViroPharma. A Bygum has been involved in clinical research or educational events involving CSL Behring, Jerini AG/Shire, Sobi, and ViroPharma; K Beusterien and E Hautamaki work for Oxford Outcomes, Inc., an ICON plc company, which consults for ViroPharma. Z Sisic is an employee of ViroPharma. S Wait receives consulting fees from ViroPharma. H Balle Boysen is the Executive Director of HAEi–International Patient Organization for C1 Inhibitor Deficiencies, which receives funding from most pharmaceutical companies, including ViroPharma Address correspondence and reprint requests to Teresa Caballero, M.D., Ph.D., Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz), Biomedical Research Network on Rare Diseases U754 (CIBERER), University Hospital La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain E-mail address: [email protected] Published online November 22, 2013 Copyright © 2014, OceanSide Publications, Inc., U.S.A.
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ereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recur-
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rent attacks of swelling, typically in the abdomen, extremities, face, larynx, and/or urogenital region.1– 6 Attacks vary unpredictably with respect to severity and frequency and can be life-threatening because of risk of asphyxiation.4,7,8 HAE symptoms often begin in early childhood and persist throughout patients’ lives. The disease presentation may also vary unpredictably throughout a patient’s life9 and an accurate diagnosis may be delayed for ⱖ10 years.2,5,10 Significant advances have been made in the clinical management of HAE, which have improved outcomes. Treatment strategies include medications for acute attacks, shortterm (preprocedural) prophylaxis, and long-term prophylaxis to minimize the frequency and severity of attacks.11–16 The uncertainty surrounding the onset of an attack can be very anxiety provoking for patients. A 2010 study of the burden of HAE in the United States found that HAE had a substantial emotional impact on patients.17 Based on the Hamilton Depression Inventory– Short Form, 43% of HAE patients had scores indicative of clinically significant depressive symptomatology. Interventional studies in HAE including the healthrelated quality of life (HRQL) measurement largely have used general health status measures, such as the Short Form 36, and they have shown improvements in several HRQL areas, including both physical and psychological parameters.18 –21 However, one may expect that HAE-specific measures of HRQL would be more
Delivered Publishing 2015 Allergyby and Asthma Technology Proceedingsto: University of California - San Francisco IP: 169.230.243.252 On: Thu, 16 Apr47 18:44:49 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
sensitive than generic measures and thus be able to capture more subtle effects of the condition on individuals. Historically, HAE has been defined largely by the physical severity and frequency of attacks.4,11 As such, the broader consequences of HAE on patients’ lives are not well understood. The objective of the HAE Burden of Illness Study in Europe (HAE-BOIS-Europe) was thus to comprehensively characterize the clinical characteristics of HAE and the impact of the disease on emotional well-being and daily life. METHODS The HAE Burden of Illness Study in Europe (HAEBOIS-Europe) assessed the real-world experience of HAE from the patient perspective in Spain, Germany, and Denmark. This cross-sectional study involved patient completion of a one-time web- or paper-based survey (depending on participant preference). Data collection took place in May–December 2011. The survey included items on clinical characteristics and physical and emotional effects, including the Hospital Anxiety and Depression Scale (HADS). Data collection included retrospective information and sought to explore the hypothesis that the impact of HAE is not limited to the time of attacks. Patients were asked about their most recent attack, as well as about how they felt over the last 6 months between attacks. All data were self-reported. Patients at least 12 years of age who were diagnosed with HAE type I or type II were recruited from patient organizations and from clinical practice via centers of excellence. Before recruitment, the study protocol and survey were reviewed and approved by the ethics review boards of each Center per their requirements. Subjects provided informed consent before beginning the survey. The full methodology is described in a study by Bygum et al.22 Severity of pain of the last attack was self-defined and reported as “no pain,” “mild,” “moderate,” or “severe” pain. Severity of swelling was defined as “mild (noticeable symptoms but they did not affect your daily activities),” “moderate (you wanted intervention for symptoms during the attack or your daily activities were affected),” or “severe (treatment or intervention was required or you were unable to perform daily activities).” Patients were asked to indicate the extent to which their most recent attack affected their ability to perform their daily activities, rated on an 11-point numeric rating response scale from “HAE attack did not affect my daily activities” to “HAE attack completely prevented me from doing my daily activities”; a similar question was asked in relation to how HAE has affected their ability to perform their daily activities during the past 6 months between attacks. Five HAE-specific anxiety items were included:
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“having an HAE attack in the future,” “the potential of transferring HAE to your children,” and “going on vacation/traveling,” which had 11-point numeric rating response scales; and “sudden feelings of panic” and “distressed about HAE attacks/symptoms,” which had 5-point Likert response scales. These five items were analyzed at the item level and they also were averaged together to create an HAE-specific anxiety score. The survey also included the HADS,23 which is comprised of two subscales that delineate between anxiety and depression. Subscale scores were calculated following developer guidelines, with scores of 0 –7 indicating the absence of symptomatology, scores of 8 –10 indicating mild symptomatology, and scores of 11–21 indicating moderate-to-severe symptomatology. Analyses were primarily descriptive, reporting means and frequencies. Differences among selected subgroups were explored using t-tests and chi-square tests for continuous and categorical variables, respectively. Mixed linear regression models also were developed to evaluate associations between potential explanatory variables and anxiety, including both the average of the five HAE-specific anxiety items and the HADS anxiety score. Potential explanatory variables included in the model were the severity of the last attack (average of pain severity and swelling severity, which was scaled from a categorical to a continuous variable for incorporation into the model), attack frequency (⬍1/mo, ⱖ1/mo but ⬍1/wk, or ⱖ1/wk), duration of swelling of the last attack (scaled from a categorical variable of ⬍2 hours to ⬎4 days to a continuous variable for incorporation into the model), use of long-term prophylaxis (by type), having medication at home to treat attacks, country, age, and gender.
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RESULTS A total of 186 patients participated in the study. Table 1 reports demographic and most recent attack characteristics by country. Across countries, 59% reported having an attack at least once a month, 67% reported moderate-to-severe pain during their last attack, and 74% reported moderate-to-severe swelling. Patients experienced an average delay in HAE diagnosis of 12 years after symptom onset. Compared with patients with attacks less than once a week (n ⫽ 147), patients with an attack at least once a week (n ⫽ 39) were younger at symptom onset (8 versus 12 years; p ⫽ 0.024). A total of 164 patients (88%) had an attack in the past 6 months, occurring a mean of 38 (SD 48) days ago. The most common body sites affected were the abdomen (32%) and extremities (27%); less common areas included the genitals or buttocks (7%) and face/ upper airway (5%). In 24% of patients, the attack occurred in more than one site. Pain and swelling were correlated (r ⫽ 0.58; p ⬍ 0.001; Fig. 1).
Delivered by Publishing Technology to: University of California - San Francisco January–February IP: 169.230.243.252 On: Vol. Thu,35, 16 No. Apr 2015 48 2014, 1 18:44:49 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
Table 1 Demographic data and attack characteristics Spain (n ⴝ 69) Germany (n ⴝ 66) Denmark (n ⴝ 51) All (n ⴝ 186) Age (yr; mean ⫾ SD) Gender Male Female Age of symptom onset (yr; mean ⫾ SD) Age of diagnosis (yr; mean ⫾ SD) Delay in diagnosis (mean ⫾ SD) Attack frequency ⬎1/wk ⬎1/mo ⬎1/yr ⬍1/yr Had an attack in the past 6 mo Pain of most recent attack* None/mild Moderate Severe Duration of swelling of most recent attack* ⬍2 hr 2–4 hr 4–12 hr 12–24 hr 2 days 3 days 4 days ⬎4 days
41 ⫾ 13
44 ⫾ 16
44 ⫾ 18
43 ⫾ 16
30 (43%) 39 (57%) 12 ⫾ 8 22 ⫾ 14 10 ⫾ 13
18 (27%) 48 (73%) 11 ⫾ 9 25 ⫾ 15 14 ⫾ 15
26 (51%) 25 (49%) 10 ⫾ 8 23 ⫾ 17 13 ⫾ 16
74 (40%) 112 (60%) 11 ⫾ 8 24 ⫾ 15 12 ⫾ 15
3 (4%) 27 (39%) 33 (48%) 6 (9%) 58 (84%)
28 (42%) 21 (32%) 17 (26%) 0 (0%) 62 (94%)
19 (37%) 22 (43%) 8 (16%) 2 (4%) 44 (86%)
23 (40%) 22 (38%) 13 (22%)
18 (29%) 31 (50%) 13 (21%)
13 (30%) 21 (48%) 10 (23%)
54 (33%) 74 (45%) 36 (22%)
0 (0%) 2 (3%) 6 (10%) 12 (21%) 17 (29%) 15 (26%) 3 (5%) 3 (5%)
4 (6%) 11 (18%) 18 (29%) 13 (21%) 7 (11%) 5 (8%) 1 (2%) 3 (5%)
0 (0%) 4 (9%) 7 (16%) 6 (14%) 12 (27%) 10 (23%) 3 (7%) 2 (5%)
4 (2%) 17 (13%) 31 (19%) 31 (19%) 36 (22%) 30 (18%) 7 (4%) 8 (5%)
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Y P 39 (21%) 70 (38%) 69 (37%) 8 (4%) 164 (88%)
*Among subjects with an attack in the past 6 mo (n ⫽164). SD ⫽ standard deviation. 100%
Pain
Swelling
Patients (%)
80%
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60%
45%
40%
45%
33%
26%
29% 22%
20%
0%
Mild
Moderate
Severe
Figure 1. Distribution of patients by paina and swellingb severity of last attack (n ⫽ 164).
The vast majority (91%) reported having medication at home to treat their attacks, although it was not specified whether the medication was indicated for the acute treatment of HAE attacks. Overall, 66% of patients treated their attack with medication specific to the treatment of acute HAE attacks (although the dosage was not collected); 12% used medication not indicated for the treatment of acute HAE attacks (including attenuated androgens and tranexamic acid). Earlier treatment of the attack was correlated with a shorter
duration of swelling (r ⫽ 0.43; p ⬍ 0.001); however, even patients who treated early had a relatively long duration of swelling. Specifically, among patients who treated within 1 hour of symptom onset (n ⫽ 49), the duration of swelling lasted a median of 12–24 hours. The impact of the attack on daily activities did not vary significantly by attack location; the median duration prevented from daily activities during the last attack was similar for attacks in an extremity or the genitals/ buttocks as for attacks in the respiratory/laryngeal area (Fig. 2). However, the likelihood of treating the attack varied by body site affected, with attacks in the face/neck or respiratory/laryngeal areas treated at a rate of 100% and attacks involving the genitals or buttocks treated the least frequently at a rate of 58%. Higher attack pain severity was associated with a greater impact on ability to perform daily activities (Fig. 3). Patients also reported that HAE impacted their ability to perform daily activities between attacks (mean ⫽ 1.9 on a scale from 0 to 10 [higher worse]). For each of the five HAE-specific anxiety items, patients generally reported higher anxiety as pain sever-
Delivered Publishing 2015 Allergyby and Asthma Technology Proceedingsto: University of California - San Francisco IP: 169.230.243.252 On: Thu, 16 Apr49 18:44:49 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
Duration prevented from daily activities
2d 12-24h 4-12h
2-4h
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ABSTRACT Hereditary angioedema (HAE) is a rare but potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The broad range of consequences of HAE on patients’ lives is not well understood. The study objective was to comprehensively characterize the burden of illness and impact of HAE types I and II from the patient perspective. The HAE Burden of Illness Study in Europe was conducted in Spain, Germany, and Denmark to assess the real-world experience of HAE from the patient perspective via a one-time survey, which included items on clinical characteristics and physical and emotional impacts. One hundred eighty-six patients participated; 59% reported having an attack at least once a month, 67% reported moderate-to-severe pain during their last attack, and 74% reported moderate-to-severe swelling. The most common sites of the last attack were the abdomen and extremities; 24% experienced an attack in more than one site. The impact of HAE on daily activities was high during attacks and did not vary significantly by body site affected; patients also reported that HAE impacted their daily activities between attacks. Patients reported substantial anxiety about future attacks, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial impairment physically and emotionally both during and between attacks. A better understanding of these effects may help in the clinical management of HAE patients. (Allergy Asthma Proc 35:47–53, 2014; doi: 10.2500/aap.2013.34.3685)
H
1
From the Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz), Biomedical Research Network on Rare Diseases U754 (CIBERER), University Hospital La Paz, Madrid, Spain, 2Pediatric Clinic, University Hospital Frankfurt, Goethe University, Frankfurt, Germany, 3HAE Centre Denmark, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark, 4Oxford Outcomes, Inc., Bethesda, Maryland, 5ViroPharma, Chatsworth House, Maidenhead, United Kingdom, 6SHW Health, Ltd., London, United Kingdom, and 7HAEi–International Patient Organization for C1 Inhibitor Deficiencies, Hasselager, Denmark Presented at the European Academy of Allergy and Clinical Immunology Congress, June 16–20, 2012, Geneva, Switzerland, and the European Society for Immunodeficiencies Biennial Meeting, October 3–6, 2012, Florence, Italy Funded by by ViroPharma SPRL-BVBA T Caballero, received sponsorship for educational purposes, has been paid for providing consultancy services, or has taken part in clinical trials sponsored by Jerini AG/Shire, CSL-Behring, Pharming NV, Sobi, and ViroPharma. E Aygo¨en-Pu¨rsu¨n, has received sponsorship for educational purposes and has provided consultancy services or has participated in clinical trials sponsored by CSL-Behring, Jerini AG/Shire, Sobi, and ViroPharma. A Bygum has been involved in clinical research or educational events involving CSL Behring, Jerini AG/Shire, Sobi, and ViroPharma; K Beusterien and E Hautamaki work for Oxford Outcomes, Inc., an ICON plc company, which consults for ViroPharma. Z Sisic is an employee of ViroPharma. S Wait receives consulting fees from ViroPharma. H Balle Boysen is the Executive Director of HAEi–International Patient Organization for C1 Inhibitor Deficiencies, which receives funding from most pharmaceutical companies, including ViroPharma Address correspondence and reprint requests to Teresa Caballero, M.D., Ph.D., Allergy Department, Hospital La Paz Institute for Health Research (IdiPaz), Biomedical Research Network on Rare Diseases U754 (CIBERER), University Hospital La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain E-mail address: [email protected] Published online November 22, 2013 Copyright © 2014, OceanSide Publications, Inc., U.S.A.
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ereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recur-
O C
rent attacks of swelling, typically in the abdomen, extremities, face, larynx, and/or urogenital region.1– 6 Attacks vary unpredictably with respect to severity and frequency and can be life-threatening because of risk of asphyxiation.4,7,8 HAE symptoms often begin in early childhood and persist throughout patients’ lives. The disease presentation may also vary unpredictably throughout a patient’s life9 and an accurate diagnosis may be delayed for ⱖ10 years.2,5,10 Significant advances have been made in the clinical management of HAE, which have improved outcomes. Treatment strategies include medications for acute attacks, shortterm (preprocedural) prophylaxis, and long-term prophylaxis to minimize the frequency and severity of attacks.11–16 The uncertainty surrounding the onset of an attack can be very anxiety provoking for patients. A 2010 study of the burden of HAE in the United States found that HAE had a substantial emotional impact on patients.17 Based on the Hamilton Depression Inventory– Short Form, 43% of HAE patients had scores indicative of clinically significant depressive symptomatology. Interventional studies in HAE including the healthrelated quality of life (HRQL) measurement largely have used general health status measures, such as the Short Form 36, and they have shown improvements in several HRQL areas, including both physical and psychological parameters.18 –21 However, one may expect that HAE-specific measures of HRQL would be more
Delivered Publishing 2015 Allergyby and Asthma Technology Proceedingsto: University of California - San Francisco IP: 169.230.243.252 On: Thu, 16 Apr47 18:44:49 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
sensitive than generic measures and thus be able to capture more subtle effects of the condition on individuals. Historically, HAE has been defined largely by the physical severity and frequency of attacks.4,11 As such, the broader consequences of HAE on patients’ lives are not well understood. The objective of the HAE Burden of Illness Study in Europe (HAE-BOIS-Europe) was thus to comprehensively characterize the clinical characteristics of HAE and the impact of the disease on emotional well-being and daily life. METHODS The HAE Burden of Illness Study in Europe (HAEBOIS-Europe) assessed the real-world experience of HAE from the patient perspective in Spain, Germany, and Denmark. This cross-sectional study involved patient completion of a one-time web- or paper-based survey (depending on participant preference). Data collection took place in May–December 2011. The survey included items on clinical characteristics and physical and emotional effects, including the Hospital Anxiety and Depression Scale (HADS). Data collection included retrospective information and sought to explore the hypothesis that the impact of HAE is not limited to the time of attacks. Patients were asked about their most recent attack, as well as about how they felt over the last 6 months between attacks. All data were self-reported. Patients at least 12 years of age who were diagnosed with HAE type I or type II were recruited from patient organizations and from clinical practice via centers of excellence. Before recruitment, the study protocol and survey were reviewed and approved by the ethics review boards of each Center per their requirements. Subjects provided informed consent before beginning the survey. The full methodology is described in a study by Bygum et al.22 Severity of pain of the last attack was self-defined and reported as “no pain,” “mild,” “moderate,” or “severe” pain. Severity of swelling was defined as “mild (noticeable symptoms but they did not affect your daily activities),” “moderate (you wanted intervention for symptoms during the attack or your daily activities were affected),” or “severe (treatment or intervention was required or you were unable to perform daily activities).” Patients were asked to indicate the extent to which their most recent attack affected their ability to perform their daily activities, rated on an 11-point numeric rating response scale from “HAE attack did not affect my daily activities” to “HAE attack completely prevented me from doing my daily activities”; a similar question was asked in relation to how HAE has affected their ability to perform their daily activities during the past 6 months between attacks. Five HAE-specific anxiety items were included:
O D
“having an HAE attack in the future,” “the potential of transferring HAE to your children,” and “going on vacation/traveling,” which had 11-point numeric rating response scales; and “sudden feelings of panic” and “distressed about HAE attacks/symptoms,” which had 5-point Likert response scales. These five items were analyzed at the item level and they also were averaged together to create an HAE-specific anxiety score. The survey also included the HADS,23 which is comprised of two subscales that delineate between anxiety and depression. Subscale scores were calculated following developer guidelines, with scores of 0 –7 indicating the absence of symptomatology, scores of 8 –10 indicating mild symptomatology, and scores of 11–21 indicating moderate-to-severe symptomatology. Analyses were primarily descriptive, reporting means and frequencies. Differences among selected subgroups were explored using t-tests and chi-square tests for continuous and categorical variables, respectively. Mixed linear regression models also were developed to evaluate associations between potential explanatory variables and anxiety, including both the average of the five HAE-specific anxiety items and the HADS anxiety score. Potential explanatory variables included in the model were the severity of the last attack (average of pain severity and swelling severity, which was scaled from a categorical to a continuous variable for incorporation into the model), attack frequency (⬍1/mo, ⱖ1/mo but ⬍1/wk, or ⱖ1/wk), duration of swelling of the last attack (scaled from a categorical variable of ⬍2 hours to ⬎4 days to a continuous variable for incorporation into the model), use of long-term prophylaxis (by type), having medication at home to treat attacks, country, age, and gender.
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RESULTS A total of 186 patients participated in the study. Table 1 reports demographic and most recent attack characteristics by country. Across countries, 59% reported having an attack at least once a month, 67% reported moderate-to-severe pain during their last attack, and 74% reported moderate-to-severe swelling. Patients experienced an average delay in HAE diagnosis of 12 years after symptom onset. Compared with patients with attacks less than once a week (n ⫽ 147), patients with an attack at least once a week (n ⫽ 39) were younger at symptom onset (8 versus 12 years; p ⫽ 0.024). A total of 164 patients (88%) had an attack in the past 6 months, occurring a mean of 38 (SD 48) days ago. The most common body sites affected were the abdomen (32%) and extremities (27%); less common areas included the genitals or buttocks (7%) and face/ upper airway (5%). In 24% of patients, the attack occurred in more than one site. Pain and swelling were correlated (r ⫽ 0.58; p ⬍ 0.001; Fig. 1).
Delivered by Publishing Technology to: University of California - San Francisco January–February IP: 169.230.243.252 On: Vol. Thu,35, 16 No. Apr 2015 48 2014, 1 18:44:49 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
Table 1 Demographic data and attack characteristics Spain (n ⴝ 69) Germany (n ⴝ 66) Denmark (n ⴝ 51) All (n ⴝ 186) Age (yr; mean ⫾ SD) Gender Male Female Age of symptom onset (yr; mean ⫾ SD) Age of diagnosis (yr; mean ⫾ SD) Delay in diagnosis (mean ⫾ SD) Attack frequency ⬎1/wk ⬎1/mo ⬎1/yr ⬍1/yr Had an attack in the past 6 mo Pain of most recent attack* None/mild Moderate Severe Duration of swelling of most recent attack* ⬍2 hr 2–4 hr 4–12 hr 12–24 hr 2 days 3 days 4 days ⬎4 days
41 ⫾ 13
44 ⫾ 16
44 ⫾ 18
43 ⫾ 16
30 (43%) 39 (57%) 12 ⫾ 8 22 ⫾ 14 10 ⫾ 13
18 (27%) 48 (73%) 11 ⫾ 9 25 ⫾ 15 14 ⫾ 15
26 (51%) 25 (49%) 10 ⫾ 8 23 ⫾ 17 13 ⫾ 16
74 (40%) 112 (60%) 11 ⫾ 8 24 ⫾ 15 12 ⫾ 15
3 (4%) 27 (39%) 33 (48%) 6 (9%) 58 (84%)
28 (42%) 21 (32%) 17 (26%) 0 (0%) 62 (94%)
19 (37%) 22 (43%) 8 (16%) 2 (4%) 44 (86%)
23 (40%) 22 (38%) 13 (22%)
18 (29%) 31 (50%) 13 (21%)
13 (30%) 21 (48%) 10 (23%)
54 (33%) 74 (45%) 36 (22%)
0 (0%) 2 (3%) 6 (10%) 12 (21%) 17 (29%) 15 (26%) 3 (5%) 3 (5%)
4 (6%) 11 (18%) 18 (29%) 13 (21%) 7 (11%) 5 (8%) 1 (2%) 3 (5%)
0 (0%) 4 (9%) 7 (16%) 6 (14%) 12 (27%) 10 (23%) 3 (7%) 2 (5%)
4 (2%) 17 (13%) 31 (19%) 31 (19%) 36 (22%) 30 (18%) 7 (4%) 8 (5%)
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Y P 39 (21%) 70 (38%) 69 (37%) 8 (4%) 164 (88%)
*Among subjects with an attack in the past 6 mo (n ⫽164). SD ⫽ standard deviation. 100%
Pain
Swelling
Patients (%)
80%
O D
60%
45%
40%
45%
33%
26%
29% 22%
20%
0%
Mild
Moderate
Severe
Figure 1. Distribution of patients by paina and swellingb severity of last attack (n ⫽ 164).
The vast majority (91%) reported having medication at home to treat their attacks, although it was not specified whether the medication was indicated for the acute treatment of HAE attacks. Overall, 66% of patients treated their attack with medication specific to the treatment of acute HAE attacks (although the dosage was not collected); 12% used medication not indicated for the treatment of acute HAE attacks (including attenuated androgens and tranexamic acid). Earlier treatment of the attack was correlated with a shorter
duration of swelling (r ⫽ 0.43; p ⬍ 0.001); however, even patients who treated early had a relatively long duration of swelling. Specifically, among patients who treated within 1 hour of symptom onset (n ⫽ 49), the duration of swelling lasted a median of 12–24 hours. The impact of the attack on daily activities did not vary significantly by attack location; the median duration prevented from daily activities during the last attack was similar for attacks in an extremity or the genitals/ buttocks as for attacks in the respiratory/laryngeal area (Fig. 2). However, the likelihood of treating the attack varied by body site affected, with attacks in the face/neck or respiratory/laryngeal areas treated at a rate of 100% and attacks involving the genitals or buttocks treated the least frequently at a rate of 58%. Higher attack pain severity was associated with a greater impact on ability to perform daily activities (Fig. 3). Patients also reported that HAE impacted their ability to perform daily activities between attacks (mean ⫽ 1.9 on a scale from 0 to 10 [higher worse]). For each of the five HAE-specific anxiety items, patients generally reported higher anxiety as pain sever-
Delivered Publishing 2015 Allergyby and Asthma Technology Proceedingsto: University of California - San Francisco IP: 169.230.243.252 On: Thu, 16 Apr49 18:44:49 Copyright (c) Oceanside Publications, Inc. All rights reserved. For permission to copy go to https://www.oceansidepubl.com/permission.htm
Duration prevented from daily activities
2d 12-24h 4-12h
2-4h
Y P
