Background• Subspecialist care and intense therapy are frequently necessary to treat severe

asthma, which affects approximately 5–10% of patients with asthma1,2

• Severe asthma significantly reduces patients’ health-related quality of life (HRQoL) as well as their overall activity and work productivity

• There are no contemporary estimates of HRQoL and activity/productivity from a national, real-world sample of U.S. adults with severe asthma

Methods • CHRONICLE (ClinicalTrials.gov Identifier: NCT03373045) is an ongoing,

noninterventional, observational study of U.S. adults with severe asthma treated by allergists/immunologists or pulmonologists

• Protocol-eligible patients are adults with asthma receiving biologic therapy and/or maintenance systemic corticosteroids (mSCS) and/or those uncontrolled (according to European Respiratory Society/American Thoracic Society criteria) on high-dosage inhaled corticosteroids and additional controllers (HD ICS+)

• At enrollment, patients were asked to complete the St. George’s Respiratory Questionnaire (SGRQ),3 including its question on overall health assessment, and the asthma-specific Work Productivity and Activity Impairment (WPAI)4 questionnaire online

- The 50-question SGRQ references the prior 3 months and assesses respiratory symptoms, activity limitations, and psycho-social impacts; scores range from 0 to 100, with 0 representing perfect health and 100 representing maximum impairment

• Patient-reported overall health is captured via a single, separately scored, item in the SGRQ using a 5-point verbal rating scale: Very Good, Good, Fair, Poor, Very Poor

- The WPAI references the prior 7 days and captures work absenteeism, work presenteeism, total work productivity loss (absenteeism plus presenteeism), and patient-reported overall activity impairment; WPAI scores represent the percentage of work impairment (0–100%)

• SGRQ and WPAI responses were summarized overall by treatment category for patients enrolled from February 2018 to February 2019. SGRQ scores were also summarized by patient-reported health

• Further analyses of the SGRQ responses were conducted to describe the following:

- The correlation between scores and patients’ overall self-assessment of their health

- The frequency of specific disease effects captured by true/false and free response questions

- Patient clusters based on concordance/discordance of SGRQ domain scores

Results • At the time of this analysis, a total of 796 patients were enrolled across 89 sites

• Overall, 482 (61%) patients completed ≥1 questionnaire at enrollment

• Patient demographics and other characteristics were generally similar for those completing questionnaires and all patients enrolled (Table 1)

Acknowledgments The CHRONICLE study is funded by AstraZeneca. Medical writing support was provided by Dan Jackson, PhD, of MedErgy (Yardley, PA, United States), which was in accordance with Good Publication Practice (GPP3) guidelines and funded by AstraZeneca (Wilmington, DE, United States).

References1. Chung KF, et al. Eur Respir J. 2014;43:343–73.2. Global Initiative for Asthma. Global strategy for

asthma management and prevention. http://www.ginasthma.org/. Accessed August 7, 2019.

3. Jones PW, et al. Am Rev Respir Dis. 1992;145:1321–7.

4. Chen H, et al. Value Health. 2008;11:231–9.

DisclosuresW Soong: Consultant — AstraZeneca, Genentech, Regeneron, Sanofi, Novartis, Teva; Speaker — AstraZeneca, Optinose, Regeneron, Sanofi, Novartis; Research — AstraZeneca, Genentech, Regeneron, Sanofi, Novartis, Bond Avillion. BE Chipps: Advisory boards, consultant, and speaker — AstraZeneca, Boehringer Ingelheim, Genentech, Novartis, Regeneron, Sanofi Genzyme. J Trevor: Consultant — AstraZeneca; Advisory boards — AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim. W Carr: Speaker — AstraZeneca, Teva, Boehringer Ingelheim, Regeneron, Sanofi; Consultant — AstraZeneca, Teva, Boehringer Ingelheim, Regeneron, Sanofi, Circassia, CSL Behring, Genentech, GlaxoSmithKline, Horizon Pharma, Kaléo, Mylan, Pfizer, Shire, Meda, Baxalta, Novartis, Greer Laboratories, Alcon Laboratories, Valeant Pharmaceuticals, Grifols, Aerocrine. S O’Quinn: Employee and shareholder — AstraZeneca. L Belton: Contractor — AstraZeneca. F Trudo: Employee and shareholder — AstraZeneca. CS Ambrose: Employee — AstraZeneca.

Table 1. Patient Demographics and Clinical Characteristics at Enrollmenta

All enrolled (N=796)

Completed enrollment

questionnaires (N=481)

Age at enrollment, yMean (SD)Median (range)

54 (14)55 (18–89)

53 (16)55 (18–83)

Female sex, % 67% 68%

Race, %WhiteBlackOther

77%16%7%

82%12%6%

Hispanic or Latino ethnicity, % 8% 7%

BMI, kg/m2

Mean (SD)Median (range)

33 (8)31 (16–70)

33 (8)31 (27–38)

Care by subspecialist at site, %Allergist/immunologistPulmonologistAllergist/immunologist and pulmonologist

45%43%11%

49%38%13%

Insurance, %CommercialMedicareMedicaidUninsuredOtherb

63%22%9%1%5%

66%22%5%1%5%

Residential area, %UrbanSuburbanRuralMissing

26%50%22%2%

24%52%22%2%

Smoking status, %NeverFormerCurrent

68%29%3%

67%28%4%

Employment status, %Employed full-timeEmployed part-timeSelf-employedHomemakerFull-time studentRetiredDisabled due to asthmaDisabled due to nonasthma conditionUnemployedc Missing

43%6%3%4% 1%

22%8%5%5%3%

43%6%3%5%2%22%8%4%4%2%

Education level, %Some high school or lessGraduated high schoolCollegeGraduate schoolMissing

5%21%48%22%5%

4%21%47%22%5%

Enrollment treatment class, %Uncontrolled on high-dosage ICS/LABA onlyAny monoclonal antibody

OmalizumabNon-omalizumab

Systemic corticosteroids or immunosuppressant

19%77%41%36%13%

19%77%44%34%13%

Exacerbations 12 months prior to enrollmentMean number of confirmed exacerbations per patient, n 1.1 1.1

BMI, body mass index; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; SD, standard deviation. aPercentages may not sum to 100% as a result of rounding. b“Other” includes “other government insurance” and “other.” c“Unemployed” does not include retired, disabled, or homemaker.

Health-related Quality of Life and Productivity Among a Real-world Cohort of Severe Asthma Patients in the United StatesWeily Soong1,*, Bradley E. Chipps2, Jennifer Trevor3, Warner Carr4, Sean O’Quinn5, Laura Belton6, Frank Trudo7, Christopher S. Ambrose5

1Alabama Allergy & Asthma Center, Birmingham, AL, United States; 2Capital Allergy & Respiratory Disease Center, Sacramento, CA, United States; 3University of Alabama at Birmingham, Birmingham, AL, United States; 4Allergy & Asthma Associates of Southern California, Mission Viejo, CA, United States; 5AstraZeneca, Gaithersburg, MD, United States; 6AstraZeneca, Cambridge, United Kingdom; 7AstraZeneca, Wilmington, DE, United States.

*Presenting author.

Poster presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting; March 13–16, 2020; Philadelphia, PA, United States.

Poster # 654

SGRQ Results• 481 patients completed the SGRQ questionnaire at enrollment

• Patients receiving biologic therapy (n=370), mSCS (n=64), and HD ICS+ only (n=91) had mean total SGRQ scores of 39, 58, and 45, respectively (Figure 1A)

- Among those treatment categories, 54%, 19%, and 55% of patients, respectively, reported Good or Very Good health (Figure 1B)

Figure 1. A) Mean (±SD) SGRQ scores, and B) percentage of patients reporting Good or Very Good health, according to treatment category at enrollment.

Symptom score Activity score Impacts score Total score100

90

80

70

60

SG

RQ

sco

re

50

40

30

20

10

0Overall (N=481) Biologics (n=370) mSCS (n=64) HD ICS+ (n=91)

100

90

80

70

60

Pat

ient

s re

po

rtin

g G

oo

do

r V

ery

Go

od

hea

lth

(%)

A.

B.

50

40

30

20

10

0HD ICS+ (n=91)mSCS (n=64)Biologics (N=370)

55%

19%

54%

HD ICS+, high-dosage inhaled corticosteroids and additional controllers; mSCS, maintenance systemic corticosteroids; SD, standard deviation; SGRQ, St. George’s Respiratory Questionnaire.

• At the subgroup level, SGRQ scores were consistent with patient-reported health; however, at the patient level, there was significant variability (Figure 2)

Figure 2. SGRQ scores according to patient-reported health.a,b

100

90

80

70

60

SG

RQ

sco

re

Patient-reported health

50

40

30

20

10

0Very Poor (n=7) Poor (n=54) Fair (n=169) Good (n=201) Very Good (n=46)

Symptom score Activity score Impacts score Total score

SGRQ, St. George’s Respiratory Questionnaire. a4 respondents with incomplete or missing data were excluded. bThe interquartile range is represented by a filled box. The bar represents the median value and the X represents the mean. Whiskers represent the minimum and maximum observation, accounting for any outliers. Outliers are represented by a filled circle.

• Among the 39 true/false questions about specific disease effects in the SGRQ, the most commonly reported effects were shortness of breath from sports/exercise, hills, severe exertion, and stairs (Figure 3)

- Using free text responses, patients reported other important activities for which severe asthma might limit their participation; these free text responses are summarized by a word cloud (Figure 4)

Figure 3. Percentage of patients responding true to specific disease effects collected by the SGRQ.a

Cannot move from bed/chairCannot shop

Cannot do household choresCannot bathe

Cannot go to entertainmentI am frail/invalid

Treatment doesn’t help muchTreatment interferes with life

Treatment is embarrassingSOB from sitting/lying

Long time for washing/dressingUnpleasant treatment side effects

Everything too much effortExercise not safe

SOB from washing/dressingNuisance to friends

Don’t expect improvementCoughing hurts

SOB when talkingSOB when bending over

Not in controlSOB from walking in house

Embarrassment from SOB/coughSOB from walking on level ground

SOB/cough sleep disturbancePanic when can’t catch breath

Tired from coughingWalk slow

Cannot play sportsLong time for chores

Slow up stairsExhausted easily

Slow down when walking fastDif�culty with mild exertion

Dif�culty with moderate exertionSOB from stairs

Dif�culty with severe exertionSOB from hills

SOB from sports/exercise

Percentage of patients marking effect as true

0 10 20 30 40 50 60 70 80 90 100

3%

5%

10%

11%

11%

14%

14%

15%

16%

17%

17%

20%

26%

28%

29%

31%

32%

32%

34%

35%

36%

39%

42%

44%

47%

49%

49%

51%

51%

53%

61%

62%

69%

70%

82%

84%

86%

88%

89%

SGRQ, St. George’s Respiratory Questionnaire; SOB, shortness of breath. aQuestions listed in this figure are paraphrased from the SGRQ.3

Figure 4. Word cloud of patient-reported free text responses to the SGRQ prompt for “other activities that your respiratory problems may prevent you from doing”.a

SGRQ, St. George’s Respiratory Questionnaire. aThe more frequently a specific word was reported, the bigger and bolder it appears in the word cloud. Generated using WordItOut (http://worditout.com).

SGRQ Domain Score Correlations• There were strong correlations between the symptom and impacts domain scores

as well as the activity and impacts domain scores; the greatest interpatient variability was found by contrasting symptom and activity domain scores

- The median difference between symptom and activity domain scores was 14.6

• 3 patient clusters were identified using a symptom vs. activity difference of ≥15 (Figure 5):

- Cluster 1: similar symptom and activity impairment (difference <15; red)

- Cluster 2: greater symptom impairment (symptom score ≥15 higher than activity score; blue)

- Cluster 3: greater activity impairment (activity score ≥15 higher than symptom score; gray)

Figure 5. Comparison of patient SGRQ activity and symptom domain scores.

0 2010 30 50 70 9040 60 80 1000

10

20

30

40

50

60

70

80

90

100

Symptom domain score

Cluster 1

Cluster 2

Cluster 3

Act

ivit

y d

om

ain

sco

re

SGRQ, St. George’s Respiratory Questionnaire.

• Examination of mean SGRQ scores by cluster revealed the following (Figure 6):

- Clusters 1 (similar) and 3 (greater activity impairment) had similar mean impacts and total scores

- Cluster 2 (greater symptom impairment) had a lower mean impacts score and lower mean total score

- Cluster 3 (greater activity impairment) had the highest mean activity score

• Patient-reported health by cluster demonstrated that:

- Patients in cluster 2 were more likely to report Good or Very Good overall health (67% vs. 47% and 49% in clusters 1 and 3, respectively)

- Patients in cluster 1 were more likely to report Poor/Very Poor overall health (18% vs. 7% and 7% in clusters 2 and 3, respectively)

Figure 6. Mean SGRQ scores by cluster according to patient symptoms and activity impairment.

0

10

20

30

40

50

60

70

80

90

100

5562

38

56

32

66

3325

32

43

33

44

Cluster 2: greater symptoms impairment (n=100)Cluster 1: similar symptoms and activity impairment (n=243)

Cluster 3: greater activity impairment (n=134)

Total scoreImpacts scoreActivity scoreSymptom score

Mea

n S

GR

Q s

core

SGRQ, St. George’s Respiratory Questionnaire.

• U.S. patients with severe asthma had reduced HRQoL and work productivity, with less impairment among those receiving biologics and greater impairment among those receiving mSCS or HD ICS+ only

- Patient-reported health, employment, and work productivity if employed were lower among those receiving mSCS therapy, likely a result of greater disease severity, poorer symptom control, and possible side effects of mSCS therapy

• SGRQ scores correlated with patient-reported health, and free text descriptions of impairments aligned with the concepts captured by the SGRQ. These findings support the SGRQ as an appropriate measure of HRQoL in severe asthma, further validating the performance of the SGRQ among U.S. patients with severe asthma

• Most patients had a difference of <15 points between their symptom and activity impairment scores. Patients in cluster 2 (21% of the total) had greater symptom impairment compared with activity impairment (62 vs. 32, respectively). These patients had better HRQoL as measured by the SGRQ total score

• Rates of patient-reported Good or Very Good health were similar among patients treated with biologic and HD ICS+ only therapies despite HRQoL and productivity differences, suggesting that patient-reported overall health may not reveal meaningful impairment. This finding highlights the challenges of capturing the patient experience via a single item and supports the utility of assessing specific experiences

• These results also suggest that limitation of physical activity, particularly exertional activity, significantly affects quality of life among severe asthma patients

Conclusions

WPAI Results• With the WPAI (N=481), impairment was highest among mSCS patients and lowest

among biologic patients

- Biologic, mSCS, and HD ICS+ only patients had mean percentages of activity impairment due to asthma of 31%, 55%, and 38%, respectively (Figure 7)

- Among those who were employed (55%, 38%, and 53% of biologic, mSCS, and HD ICS+ only patients, respectively), mean overall work productivity loss was 19%, 38%, and 26%, respectively

Figure 7. WPAI results at enrollment according to treatment categories.a,b

HD ICS+ (n=91)mSCS (n=64)Biologics (n=370)Overall (N=481)0

102030405060708090

100

33 31

55

3826 24

4

38 342019 17

4

21 19

5

Employed patients: overall work productivity loss because of asthmaPercentage of activity impairment because of asthma

Employed patients: productivity loss while at work because of asthmaEmployed patients: percentage of work time missed because of asthma

Mea

n (%

)

HD ICS+, high-dosage inhaled corticosteroids and additional controllers; mSCS, maintenance systemic corticosteroids; WPAI, Work Productivity and Activity Impairment.aNumber of employed patients among treatment groups: overall (n=257), biologics (n=204), mSCS (n=24), HD ICS+ only (n=48).bPatients not currently employed reported their ability to complete regular daily activities.