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Mepolizumab improves activity limitation
in severe eosinophilic asthma

Frank C. Albers1, Linda M. Nelsen2,

Daniel J. Bratton3, Eric S. Bradford4, Gert-Jan Braunstahl5

1Respiratory Medical Franchise, GSK, Research Triangle Park, NC, USA;

2Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 3Clinical Statistics, GSK,

Stockley Park, Middlesex, UK; 4Respiratory Therapeutic Area, GSK, Research Triangle
Park, NC, USA; 5Department of Pulmonary Medicine, Franciscus Gasthuis and
Vlietland, Rotterdam, the Netherlands
 Disclosures

• In relation to this presentation, I declare the following, real or perceived conflicts of interest:
– This study was funded by GSK (GSK study ID: 200862; NCT02281318)
– Frank Albers, Linda Nelsen, Daniel Bratton and Eric Bradford are employees of GSK
and hold stocks/shares in GSK. Gert-Jan Braunstahl has received grant/research support
for consultations and/or speaking at conferences from Novartis, ALK-Abello, Meda
Pharma, GSK, Takeda, AstraZeneca and MSD
– Medical writing assistance in the preparation of these slides was provided by Elizabeth
Hutchinson, PhD CMPP at Fishawack Indicia Ltd, UK, which was funded by GSK
– Data on morning PEF were published in Chupp GL, et al. Lancet Respir Med
2017;5:390–400

A conflict of interest is any situation in which a speaker or immediate family members have interests, and those may cause
a conflict with the current presentation. Conflicts of interest do not preclude the delivery of the talk, but should be explicitly declared. These may include financial interests
(e.g. owning stocks of a related company, having received honoraria, consultancy fees), research interests (research support by grants or otherwise), organisational interests and gifts
 Background: mepolizumab for severe eosinophilic asthma

Maintaining activity levels and achieving good symptom control are important asthma
management goals, and reflect daily impact for patients1

Mepolizumab is an anti-IL5 therapy approved for the treatment of severe refractory

eosinophilic asthma,2 and reduces blood eosinophils to low normal levels3–6

Mepolizumab reduces exacerbation rates,3–5 reduces the need for OCS,5 and
improves HRQoL6 and FEV14,6 in patients with severe eosinophilic asthma

The impact of mepolizumab on activity limitation and symptom control in patients with
severe eosinophilic asthma was explored in the MUSCA study6

FEV1, forced expiratory volume in one second; HRQoL, health-related quality of life; IL, interleukin; OCS, oral corticosteroids
1. GINA. Global Strategy for Asthma Management and Prevention 2017. Available from www.ginasthma.org; 2. GSK. Mepolizumab summary of product characteristics 2017:
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003860/WC500198037.pdf; 3. Pavord ID et al. Lancet 2012;380:651–9;
4. Ortega HG et al. N Engl J Med 2014;371:1198–207; 5. Bel EH et al. N Engl J Med 2014;371:1189–97; 6. Chupp GL, et al. Lancet Respir Med 2017;5:390–400.
 Activity limitation: definition

“An activity limitation is defined as a long-term reduction in a person’s capacity

to perform the usual kind or amount of activities associated with his or her
age group as a result of a chronic condition”

Matsunaga NY, et al. Jornal Brasileiro de Pneumologia 2015; 41(6):502−8.

 The MUSCA study: objectives

• To assess the effect of mepolizumab on HRQoL outcomes in patients with severe refractory
eosinophilic asthma
• Here we will be reporting the effect of mepolizumab vs placebo on activity limitation, morning
PEF and asthma symptoms

Primary endpoints: change from baseline in SGRQ total score1

Secondary endpoints: FEV1, SGRQ responders, ACQ-5 score1

Other non-primary/non-secondary endpoints:

- Global Rating of Activity Limitation at Week 24
- Global Impression of Change in Activity Limitation rating at Week 24
- Morning PEF from daily eDiary1
- Daily asthma symptoms scores from daily eDiary

ACQ, Asthma Control Questionnaire; FEV1, forced expiratory volume in one second; HRQoL, health-related quality of life; PEF, peak expiratory flow; SGRQ, St George’s Respiratory Questionnaire
1. Chupp GL, et al. Lancet Respir Med 2017;5:390–400.
 Methods: study design

• MUSCA was a Phase IIIb, placebo-controlled, randomised, double-blind, parallel-group,

24-week, multicentre study in patients with severe refractory eosinophilic asthma
• Patients were randomly assigned to receive mepolizumab 100 mg SC or placebo SC on
top of standard of care, every 4 weeks for 24 weeks (final dose at Week 20)
Week 0 4 8 12 16 20 24
Visit 2 3 4 5 6 7 Exit

Mepolizumab
Visit 0 Visit 1 Visit 2 100 mg SC

Randomisation
Pre-screen Screening
1:1

Placebo SC

4-week run-in period Treatment administered

SC, subcutaneous
Chupp GL, et al. Lancet Respir Med 2017;5:390–400.
 Results: baseline characteristics and demographics
Mepolizumab Placebo
(n=274) (n=277)
Patient characteristics
Age, years, mean (SD) 50 (14) 52 (13)
Females, n (%) 149 (54) 176 (64)
Body mass index (kg/m2), mean (SD) 29 (6.6) 28 (6.2)
Duration of asthma, years, mean (SD) 20 (15) 20 (15)
Exacerbations in the 12 months prior to screening, mean (SD) 2.9 (1.9) 2.7 (1.5)
Patients with ≥1 exacerbation requiring ER visit or admission 87 (32) 92 (33)
to hospital in the 12 months before screening, n (%)
Measures of lung function
Pre-bronchodilator % predicted FEV1, mean (SD) 56 (14) 55 (15)
Morning PEF L/min, mean (SD) 295.5 (119.2) 283.9 (115.4)
Asthma symptom score, mean (SD) 1.6 (1.1) 1.5 (1.1)
Total SGRQ score 47.4 (18.1) 46.3 (18.9)
ACQ-5 score 2.2 (1.1) 2.2 (1.2)
ACQ, Asthma Control Questionnaire; ER, emergency room; FEV1, forced expiratory volume in one second; PEF, peak expiratory flow; SD, standard deviation; SGRQ, St George’s Respiratory Questionnaire
Chupp GL, et al. Lancet Respir Med 2017;5:390–400.
Methods: activity limitation

Global rating of Global impression of change in

activity limitation activity limitation

Patients were asked to rate their impression of change

Patients were asked to rate their activity limitation at
in activity limitation since the start of the study on a
each time point in the study on a 4-point scale
7-point Likert scale

Single question questionnaire Single question questionnaire

Response options: much better, better,

Response options: not limited, slightly limited,
slightly better, no change, slightly worse,
limited, very limited
worse, much worse

Assessed at Assessed at
Weeks 4, 12, 20 and 24 Weeks 4, 12, 20 and 24
Results: Global Rating of Activity Limitation
Patient responses at baseline and Week 24

Not limited Slightly limited Limited Very limited Missing

100% <1% 3% 1% 5%
7% 3% 8% 4%
90%
Proportion of patients (%)

15%
80% 20%
32% 29%
70%
60% 41%
50% 43%
40% 36% 79% 40%
71%
30% 60% 62%
20% 38%
24% 22% 28%
10%
0%
Baseline Week 24 Baseline Week 24
Mepolizumab (n=274) Placebo (n=277)
 Results: Global Impression of Change in Activity Limitation*
Patient responses at Week 24

Much Better Better Slightly Better No Change Slightly worse/worse/much worse Missing

3% 5%
100%
2%
90% 5%
Proportion of patients (%)

18%
80%
70% 35%
19%
60%
50%
26% 18%
40% 76%
30% 54%
20%
20%
31%
10% 16%
0%
Mepolizumab (n=274) Placebo (n=277)

*Impression of change since start of study

Slightly worse, worse and much worse categories combined
 Results: activity limitation
Treatment difference for mepolizumab vs placebo at Week 24

Favours placebo Favours mepolizumab Odds ratio (95% CI)

Patients’ Global Rating of

1.68 (1.21, 2.32)
Activity Limitation
p=0.002

Patients’ Global Impression of

2.63 (1.93, 3.58)
Change in Activity Limitation
p<0.001

0.5 1 2 4
Odds ratio to placebo (95%CI)

CI, confidence interval; FEV1, forced expiratory volume in one second; OCS, oral corticosteroids
Note: 4 patients with missing Global Rating of Activity Limitation at baseline are not included; analysed using a proportional odds model (multinomial [ordered]
logistics generalised linear model) with terms for treatment group, region, baseline maintenance OCS therapy (OCS vs no OCS), exacerbations in the year prior
to the study, baseline % predicted FEV1, and global rating of activity limitation at baseline
Methods: eDiary assessments
0 No symptoms during the previous 24 hours

eDiary asthma parameters Symptoms for one short period during the
1
previous 24 hours

Symptoms for two or more short periods

2
Morning PEF before rescue medication during the previous 24 hours
usage (L/min)

Symptoms for most of the previous 24 hours

3
Asthma symptom score over previous which did not affect my normal daily activities
24 hours on a 6‐point scale

Symptoms for most of the previous 24 hours

4
Recorded daily and averaged over which did affect my normal activities
4-week periods

Symptoms so severe that I could not go to

5
work/school or perform normal activities
 Results: morning PEF
Mean change from baseline by 4-week period*
Mepolizumab (n=274) Placebo (n=277)
25 23.2
22.9 22.9
Mean change from baseline (L/min)

21.9 21.6
20
17.1

15

10

4.5 5.0
5 3.6 4.1 4.1
2.7

0
1–4 5–8 9–12 13–16 17–20 21–24
Weeks

Baseline morning PEF (L/min) mean (SD): 295.5 (119.2) 283.9 (115.4)

*Data collected daily on eDiary device and averaged over 4-week periods
 Results: daily asthma symptom scores
Change from baseline by 4-week period*,†
Mepolizumab (n=274) Placebo (n=277)
Weeks
1–4 5–8 9–12 13–16 17–20 21–24
0
-0.1
Mean change from baseline

-0.2
-0.2
-0.3
-0.3
-0.4
-0.4 -0.4 -0.4
-0.5
-0.5 -0.5
-0.6
-0.6 -0.6
-0.7
-0.7 -0.7 -0.7
-0.8

Baseline mean (SD) asthma symptom score: 1.6 (1.1) 1.5 (1.1)
*Data collected daily on eDiary device and averaged over 4-week periods
†Minimum score 0, maximum score 5
Summary and conclusions

• Patients’ assessment of their activity limitation at Week 24 showed significant

improvements for patients who received mepolizumab vs placebo
• Change in morning PEF from baseline was greater with mepolizumab vs
placebo from early on and throughout the study
• Mean asthma symptom scores decreased during the study for patients
receiving mepolizumab and placebo

This study demonstrates that mepolizumab add-on therapy significantly

improves patient perception of their activity and improves morning PEF
vs placebo in patients with severe refractory eosinophilic asthma