Biologika in der Therapie von schwerem Asthma: Wo stehen

Biologika in der Therapie von schwerem Asthma:

Wo stehen wir heute?

Henrik Watz

Pneumologisches Forschungsinstitut an der

LungenClinic Grosshansdorf

Airway Research Center North (ARCN)

Deutsches Zentrum für Lungenforschung(DZL)

Interessenskonflikt

• Das Pneumologische Forschungsinstitut an der LungenClinic Grosshansdorf erhielt

Kostenerstattungen für Beratung und Studiendurchführung von AB2BIO, AstraZeneca, Bayer

Health Care, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Merck, Novartis, Pfizer, TEVA,

Revotar, Sanofi, Sterna, Roche.

• Henrik Watz erhielt Honorare für Beratung und Vorträge sowie Erstattung von Reisekosten

und Kongressgebühren der Firmen AstraZeneca, Boehringer Ingelheim, BerlinChemie, Chiesi,

GlaxoSmithKline, Novartis, Sanofi, Roche.

2

Global burden of asthma

23–56% uncontrolled

asthma7–9

358 million people worldwide6

↑ morbidity and

mortality11–

14

EU-5a,2

4‒10 %

China

2,1 %3

Japan

2,4%4

USA

7,6 %1

Australia

14,7 %3

There were 397.000 deaths attributed to asthma in 2015.5

Global asthma prevalence rates

358 million people worldwide5

23–56 % uncontrolled

asthma6–8

5‒10 %severe

asthma10

↑ morbidityand

mortality9

Accounts for > 80 % of all healthcare direct costs in asthma11

3

Uncontrolled asthma Difficult-to-treat asthma Severe asthma

• Poor symptom control (frequent symptoms or reliever use, activity limited by asthma, night waking due to asthma)

• Frequent exacerbations (≥ 2/year) requiring OCS, or serious exacerbations (≥ 1/year) requiring hos-pitalization

• Uncontrolled despite GINA Step 4−5 treatment(e.g. medium or high dose ICS with a second controller; maintenance OCS), or such treatment to maintain good symptom control and reduce the risk of exacerbations

• Asthma may appear difficult-to-treat because of modifiable factors(incorrect inhaler technique, poor adherence, smoking or comorbidities, of incorrect diagnosis)

• Uncontrolled despite GINA Step 4−5 treatment(e.g. medium or high dose ICS with a second controller; maintenance OCS), and good adherence and treatment of contributory factors or asthma that worsens when high-dose treatment is decreased

Unkontrolliert … schwierig zu therapieren … schweres Asthma

4Global Initiative for Asthma (GINA). 2020 Global Strategy for Asthma Management and Prevention. Available from: https://ginasthma.org/gina-reports/. Accessed November 2020.

Kriterien der Asthmakontrolle

GINAAny 1 of the following 4 criteria qualifies a patient as having uncontrolled asthma, despite therapy:

Frequent severe exacerbations:

• ≥ 2 exacerbations per year requiring oral corticosteroids

GINA recognizes lung function asan important indicator of future risk;therefore, FEV1 should be measured:

• At start of treatment

• 3–6 months after treatment initiation

• And periodically thereafter

Serious exacerbations:

• ≥ 1 exacerbation per year requiring hospitalization

Poor symptom control:

• Frequent symptoms or reliever use

• Activity limited by asthma

• Night waking due to asthma

FrequentOCS Use

Impaired LungFunction

SeriousExacerbations

Poor Symptom Control

Global Initiative for Asthma (GINA). 2020 Global Strategy for Asthma Management and Prevention. Available from: https://ginasthma.org/gina-reports/. Accessed November 2020. 5

Versorgungsrealität Deutschland I

21,3 % 21,0 % 20,3 %

5,2 % 5,0 % 4,7 %

38,8 % 39,2 % 40,1 %

31,7 % 31,8 % 32,1 %

3,2 % 3,0 % 2,7 %

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2015 2016 2017

Pro

po

rtio

n o

fp

ati

en

ts(%

)

Year

1A. Severity of asthma according to treatment group

Step 1

Step 2

Step 3

Step 4

Step 5

Lommatzsch et al. Respir Med 2020.

• n = 30.000

• 1039 Allgemeinpraxen

6

9,4 % 9,6 %8,9 %

0

1

2

3

4

5

6

7

8

9

10

2015 2016 2017

Pro

po

rtio

n o

fp

ati

en

ts(%

)

Year

2A. Proportion of patients with asthmareceiving OCS > 30 d/y

Versorgungsrealität Deutschland I

Lommatzsch et al. Respir Med 2020. 7

• 10−15 mg Prednisolon

• 30 % nicht Stufe 5

40,2 %

10,7 %

33,7 %

58,1 %

22,6 %

43,6 %

11,7 %

32,9 %

59,9 %

23,5 %

48,8 %

14,2 %

35,4 %

64,4 %

22,8 %

52,1 %

20,9 %

36,2 %

68,2 %

28,6 %

58,9 %

32,8 %

38,6 %

75,7 %

34,5 %

0% 20% 40% 60% 80%

Metabolic disorders

Disorders of themusculoskeletal system

Psychiatric disorders

Heart disease

Disorders of the eye

OCS long-term >180 days

OCS long-term >90 to <180 days

OCS long-term >20 to <90 days

OCS short-term frequent

OCS short-term non frequent

Versorgungsrealität Deutschland II (2015)

Taube et al. ERJ Open Res 2019.

• Krankenkassendaten

• n = 4 Mio

• 7,3 % Asthmaprävalenz

• 8,7 % HD-ICS/LABA

17,3 % OCS ( > 180 d/y)

8

1824

1139

105

1675

353

30

5096

2053

1162

82

1664

389

9

5351

2764

1214

89

2147

451

53

6666

4024

1277

138

2884

787

136

9110

5245

1342

93

3732

840

66

11253

0

2000

4000

6000

8000

10000

12000

Inpatient Outpatient Sick-leavepayments

Pharmaceutical Devicesand aids

Intensivecare

Total

OCS short-term non frequent

OCS short-term frequent

OCS long-term > 20 to < 90 days

OCS long-term > 90 to < 180 days

OCS long-term >180 days

Versorgungsrealität Deutschland II (2015)

Taube et al. ERJ Open Res 2019. 9

Therapie-Empfehlung NVL Asthma

NVL Asthma 2020. 10

Stufe 1

Bedarfstherapie:

Fixkombination aus ICS

niedrigdosiert + Formoterol1

oder

SABA

Stufe 2

Langzeittherapie:

mit ICS niedrigdosiert

+ Bedarfstherapie mit

SABA

oder

Ausschließlich

Bedarfstherapie mit

Fixkombination aus

ICS mitteldosiert

+ Formoterol1

Stufe 3

Langzeittherapie:

ICS niedrigdosiert

+ LABA (bevorzugt)

oder

ICS mitteldosiert

Stufe 4

Langzeittherapie:

ICS mittel- bis hochdosiert

+ LABA (bevorzugt)

oder


+ LABA + LAMA2

Stufe 5

Langzeittherapie:

ICS in Höchstdosis

+ LABA + LAMA2

Vorstellung bei einem in der

Behandlung von schwerem

Asthma erfahrenen

Pneumologen

und

Anti-IgE- oder Anti-IL-5-(R)-

oder Anti-IL-4-R-Antikörper

Alternativen zur Langzeittherapie in begründeten Fällen:

ICS niedrigdosiert + LAMA2

oder

ICS niedrigdosiert + LTRA


+ LABA + LTRA

oder


+ LAMA2

OCS (zusätzlich oder

alternativ)

Anti-IL4Rα therapy Anti-IgE therapy Anti-IL-5/5Rα therapies

• FeNO ≥ 25 ppb

• Blood EOS ≥ 150/µL

• Exacerbation rate

• Maintenance OCS

• Comorbidities (CRSwNP/AD)

• Total and/or specific IgE

• Skin prick test (allergological evaluation)

• Clinical characteristics (eg, weight)



• FeNO ≥ 20 ppb

• Childhood asthma



• Adult-onset asthma

• Maintenance OCS

• Comorbidities (CRSwNP)

Biomarker der Typ-2-Inflammation und

klinische Kriterien zur Auswahl des BiologikumsE

ligib

ility

crite

ria

Global Initiative for Asthma (GINA). 2020 Global Strategy for Asthma Management and Prevention. Available from: https://ginasthma.org/gina-reports/. Accessed September 2020. 11

Typ-2-Inflammation

Type 2 cytokines

IL-4 IL-13 IL-5

(clinically allergen-driven)

FeNO EOS

Type 2 biomarkers

Asthma patient populations

Allergic Eosinophilic

Type 2

IgE

Type 2 targeted biologics

Anti-IgE Anti-IL5/5R

Anti-IL-4R

Type 2 inflammation in asthma

1. Gandhi NA, et al. Nat Rev Drug Discov. 2016;15(1):35-50. 2. Katial RK, et al. J Allergy Clin Immunol Pract. 2017;5(2S):S1-S14. 3. Robinson D, et al. Clin Exp Allergy. 2017;47(2):161-175.

4. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. Updated 2020. https://ginasthma.org/gina-reports/. Accessed July 2020. 12

Kriterien der Typ-2- Inflammation und Schnittmengen

GINA1

Criteria checklist: Type 2 inflammation

Blood EOS ≥ 150 cells/µl

FeNO ≥ 20 ppb

Sputum EOS ≥ 2%

Clinically allergen driven

Need for maintenance OCS

FeNO

Total/specific IgE

EOS

ATS: American Thoracic Society; EOS, eosinophils; ERS, European Respiratory Society; FeNO, fractional exhaled nitric oxide; OCS, oral corticosteroid.

1. Global Initiative for Asthma (GINA). 2020 Global Strategy for Asthma Management and Prevention. Available from: https://ginasthma.org/gina-reports/. Accessed November 2020. 2. Chung KF, et al. Eur Respir J. 2014;43(2):343-373. 13

0

1

2

3

4

5

6

0 50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850

Ind

ivid

ua

ls%

Eosinophil count cells · μL−1

128 cells·μL−1 (geometric mean)

210 cells·μL−1 (75 % percentile)

Verteilung der EOS in der Allgemeinbevölkerung (Wien)

Hartl et al. Eur Respir J 2020. 14

0 20 40 60 80 100 120 140 160 180 200 220

Eo

sin

op

hil

ce

lls

/μL

Individual patient

6 %

48 %

46 %

300

1000

2000

3000

Variabilität der Bluteosinophilen

schweres Asthma (n = 219; 5-Jahres-Zeitraum)

Rakowski E et al. Clin Exp Allergy. 2019;49(2):163-170. 15

Medium-dose ICS treatment High-dose ICS treatment

Blo

od

eo

sin

op

hil

s (

ce

lls

/µl)

Lommatzsch et al. Thorax 2019.

4000 -

100 -

3000 -

2000 -

1000 -

500 -

560

320

Einfluss der inhalativen Kortikosteroide

16

Table 5 predicted FeNO values at the age of 50 y.

Smoking - - - - + + + +

Infection - - + + - - + +

Allergy - + - + - + - +

Height [cm]

150 11,0 12,2 12,0 13,2 8,4 9,2 9,1 10,1

160 12,1 13,4 13,2 14,6 9,2 10,2 10,0 11,1

170 13,4 14,8 14,6 16,1 10,2 11,3 11,1 12,3

180 14,8 16,4 16,1 17,8 11,3 12,5 12,2 13,6

190 16,4 18,1 17,8 19,7 12,4 13,8 13,5 15,0

Karrasch et al. Respir Med 2010.

FeNO-Interpretation: populationsbasierte Daten Deutschland

17

Anti-IL4Rα therapy Anti-IgE therapy Anti-IL-5/5Rα therapies

• FeNO ≥ 25 ppb



• Maintenance OCS

• Comorbidities (CRSwNP/AD)

• Total and/or specific IgE

• Skin prick test (allergological evaluation)

• Clinical characteristics (eg, weight)



• FeNO ≥ 20 ppb

• Childhood asthma

• Blood EOS ≥300/µL


• Adult-onset asthma

• Maintenance OCS

• Comorbidities (CRSwNP)

Biologika zur Therapie des schweren AsthmasE

ligib

ility

crite

ria

Global Initiative for Asthma (GINA). 2020 Global Strategy for Asthma Management and Prevention.

Available from: https://ginasthma.org/gina-reports/. Accessed September 2020. 18

Humbert et al. Eur Respir J 2018.

Anti-IgE: Real World Omalizumab (STELLAIR)

19

• n = 872

• 28 % OCS

• 20 mg Pred.

65,00 % 67,90 % 66,80 % 67,60 %

0 %

10 %

20 %

30 %

40 %

50 %

60 %

70 %

80 %

90 %

100 %

Responders(EOS 150)

Responders(EOS 300)

Pro

po

rtio

n o

fp

ati

en

ts(%

±9

5 C

I)

A – Responders based on physician‘sglobal evaluation (GETE)

< 150 cells/μL, n = 163 ≥ 150 cells/μL, n = 560


73,60 %

70,40 %72,30 %

70,00 %

0 %

10 %

20 %

30 %

40 %

50 %

60 %

70 %

80 %

90 %

100 %

Responders(EOS 150)

Responders(EOS 300)

Pro

po

rtio

n o

fp

ati

en

ts(%

±9

5 C

I)

B – Responders based on 40 % decreasein the annual exacerbation rate



Anti-IgE: Omalizumab

Meta-Analyse der Real-World-Studien – Reduktion der Exazerbationen

12 Months

Alfarroba 2014 1,70 0,00 23 3,13 0,00 26 0,0 % –1,43

Barnes 2013 1,70 0,00 136 3,67 0,00 136 0,0 % –1,97

Braunstahl 2013a 0,20 0,60 691 2,20 2,81 842 8,3 % –2,00 [–2,20; –1,80]

Bruselle 2009 0,95 0,00 130 2,73 0,00 130 0,0 % –1,78

Casale 2018 0,78 1,37 796 3,00 3,28 804 8,3 % –2,22 [–2,47; –1,97]

Cazzola 2010 1,00 1,29 93 4,87 4,00 139 7,9 % –3,87 [–4,58; –3,16]

Dal Negro 2011a 0,52 3,67 23 2,00 3,67 23 5,9 % –1,48 [–3,60; 0,64]

Dal Negro 2011b 0,50 0,70 23 2,10 1,10 23 8,1 % –1,60 [–2,13; –1,07]

Dal Negro 2012 0,94 0,46 16 2,06 1,12 16 8,0 % –1,12 [–1,71; –0,53]

Deschildre 2013 1,25 3,42 92 4,40 3,87 104 7,6 % –3,15 [–4,17; –2,13]

Gemicioglu 2016 0,29 0,00 17 2,57 0,00 17 0,0 % –2,28

Jahnz–Rozyk 2018 1,93 1,83 85 6,63 4,83 85 7,5 % –4,70 [–5,80; –3,60]

Ke 2018 0,60 0,75 1564 1,20 1,14 1564 8,3 % –0,60 [–0,67; –0,53]

Niven 2016 0,69 0,00 218 1,66 0,00 218 0,0 % –0,97

Steiss 2015 0,40 1,50 9 4,50 8,10 9 2,3 % –4,10 [–9,84; 1,28]

Tzortzaki 2012 0,77 0,94 60 2,27 2,82 60 7,9 % –1,50 [–2,25; –0,75]

Vennera Mdel 2012 0,71 1,30 225 3,60 3,60 263 8,1 % –2,89 [–3,36; –2,42]

Vennera Mdel 2016 3,05 4,12 71 10,77 5,94 71 6,6 % –7,72 [–9,40; –6,04]

Vieira 2014 2,20 1,50 14 7,50 4,60 15 5,3 % –5,30 [–7,76; –2,84]

Total (95 % CI) 4286 4545 100,0 % –2,75 [–3,46; –2,04]

Heterogeneity: Tau2 = 1,4598; Chi2 = 593,72; df = 13 (p < 0,01); I2 = 98 %

Test for overall effect: Z = –7,61 (p < 0,01)

Bousquet et al. JACI Practice 2021. 20

-6-4-202

Favors Omalizumab

Anti-IgE: Omalizumab

Meta-Analyse der Real-World-Studien – Reduktion der oralen Steroide

Bousquet et al. JACI Practice 2021 21

12 Months

Adachi 2018 278 3593 683 3593 8,8 % 0,41 [0,36; 0,46]

Al-Ahmad 2018a 14 65 65 65 6,2 % 0,22 [0,14; 0,35]

Ayres 2004 99 191 47 206 7,7 % 2,27 [1,71; 3,02]

Barbosa 2015 5 54 11 62 2,8 % 0,52 [0,19; 1,41]

Barnes 2013 70 136 90 136 8,3 % 0,78 [0,64; 0,95]

Braunstahl 2013a 118 734 262 916 8,4 % 0,56 [0,46; 0,68]

Brusselle 2009 106 130 100 158 8,7 % 1,29 [1,12; 1,49]

Cazzola 2010 27 93 52 142 6,8 % 0,79 [0,54; 1,16]

Dal Negro 2011a 1 23 23 23 1,4 % 0,06 [0,01; 0,30]

Dal Negro 2012 5 16 16 16 4,4 % 0,33 [0,17; 0,66]

Deschildre 2013 0 92 6 104 0,5 % 0,09 [0,00; 1,52]

Gouder 2015 4 20 9 22 2,7 % 0,49 [0,18; 1,34]

Humbert 2018 99 723 243 723 8,3 % 0,41 [0,33; 0,50]

Ke 2018 1039 1564 1303 1564 9,1 % 0,80 [0,76; 0,83]

Lafeuille 2013 315 801 1479 3044 8,9 % 0,81 [0,74; 0,89]

Velling 2011 4 13 12 13 3,5 % 0,33 [0,15; 0,76]

Verma 2011 3 17 5 17 1,9 % 060 [0,17; 2,12]

Vieira 2014 2 14 8 15 1,7 % 0,27 [0,47; 0,75]

Total (95 % CI) 4286 4545

Heterogeneity: Tau2 = 0,1627; Chi2 = 335,71, df = 17 (P < 0,01); I2 = 98 %

Test for overall effect: Z = –4,45 (P < 0,01)0,010,1110100

Favors Omalizumab

Anti-IL-5: Real World Mepolizumab (REALITI-A)

[n = 260] 0,22

[n = 45] 0,36

[n = 51] 0,46

[n = 367] 0,27

[n = 260] 1,36

[n = 45] 1,78

[n = 51] 1,74

[n = 367] 1,43

[n = 259] 1,02

[n = 45] 1,32

[n = 51] 1,76

[n = 366] 1,14

[n = 259] 4,7

[n = 45] 4,42

[n = 51] 5,01

[n = 366] 4,63

≥300 cells/μL

Baseline BEC

≥150- <300cells/μL

Baseline BEC

<150 cells/μL

Baseline BEC

Total Population

≥300 cells/μL

Baseline BEC

≥150- <300cells/μL

Baseline BEC

<150 cells/μL

Baseline BEC

Total Population

Exa

ce

rba

tio

ns

requ

irin

g

ho

sp

ita

lisation

an

d/o

r

em

erg

en

cy

de

pa

rtm

entvis

it

Clin

ica

llysig

nific

ant

exa

ce

rba

tio

ns

Harrison et al. Eur Respir J 2020. 22

Rate ratio (95 % CI) p-value

0,31 (0,27−0,35) < 0,001

0,35 (0,26−0,46)

0,40 (0,31−0,52)

0,29 (0,25−0,34)

0,23 (0,18−0,30) < 0,001

0,26 (0,17−0,41)

0,27 (0,16−0,48)

0,22 (0,16−0,30)

• n = 368

• 48 % OCS

• 15 mg Pred.

Pre-mepolizumab treatment period

12-month follow-up period

Anti-IL-5: Real World Mepolizumab (REALITI-A)

• n = 368

• 48 % OCS

• 15 mg Pred.

Harrison et al. Eur Respir J 2020. 23

0

2

4

6

8

10

12

14

16

Me

dia

n d

ail

yd

os

e m

g

Follow-up period weeks

a]

52 % reduction

from BL

n: 159 158 156 156 154 153 153 152 151 150 149 146 143 143 143

0

2

4

6

8

10

12

14

16

Me

dia

n d

ail

yd

os

e m

g


b]

51 % reduction

from BL

n: 28 28 28 28 28 27 27 27 27 27 27 26 24 24 24

0

2

4

6

8

10

12

14

16

Me

dia

n d

ail

yd

os

e m

g


c]

23 % reduction

from BL

n: 32 32 32 32 31 31 31 31 31 31 31 30 30 30 30

0

2

4

6

8

10

12

14

16

Me

dia

n d

ail

yd

os

e m

g


d]

74 % reduction

from BL

n: 98 97 95 95 94 94 94 93 92 91 90 89 88 88 88

Total population Baseline BEC <150/µl

Baseline BEC ≥150 - <300/µl Baseline BEC ≥300/µl

Anti-IL-5: Real World Reslizumab

Wechsler et al. Chest 2021. 24

86,0

47,4

12,6

71,2

40,5

14,0

2,8

31,2

0

10

20

30

40

50

60

70

80

90

100

Experienced anyexacerbation

≥ 3 daysprednisone

Increased prednisonedose for ≥ 3 days

Patients havingER care/hospitalization

for asthma

Pe

rce

nta

ge

(%)

Before reslizumab initiation After reslizumab initiationp < 0,001

N = 185 N = 87 N = 102 N = 30 N = 27 N = 6 N = 153 N = 67

Kavanagh et al. Chest 2021

• n = 130

• 74 % OCS

• 10 mg Pred.

Anti-IL5-Rα: Real World Benralizumab

25

0

2

4

6

8

10

Baseline 1 year

AE

R

A***

1,5

2,0

2,5

3,0

3,5

0 4 8 24 48

AC

Q-6

Weeks

B

***

***

2,0

2,5

3,0

3,5

4,0

4,5

5,0

0 4 8 24 48

mA

QL

Q

Weeks

C

***

***

55

60

65

70

75

0 4 8 24 48

FE

V1

(% p

red

icte

d)

Weeks

D

**

***

Kavanagh et al. Chest 2021.

• n = 130

• 74 % OCS

• 10 mg Pred.

Anti-IL5-Rα: Real World Benralizumab

26

0

5

10

15

20

25

0 6 12 18 24 30 36 42 48

Me

dia

n O

CS

do

se

(mg

/d)

Weeks since commencing benralizumab

**

***

0

25

50

75

100

0 6 12 18 24 30 36 42 48

Pro

po

rtio

n r

eq

uir

ing

≥ 5

mg

/d m

OC

S(%

)

Weeks since commencing benralizumab

Wechsler et al. ERS 2020, ms under review.

Anti-IL4-Rα: TRAVERSE (Exazerbation) Dupilumab

27

2,37(2,49) 2,27

(2,22)2,22

(1,87) 2,09(2,00)

0

0,50

1,00

1,50

2,00

2,50

Placebo/dupilumab

n = 111

Dupilumab/dupilumab

n = 421

Placebo/dupilumab

n = 423

Dupilumab/dupilumab

n = 804

Nu

mb

er

of

ex

ac

erb

ati

on

sin

th

ep

rio

rye

ar,

me

an

(SD

)

Number of exacerbations in the yearprior to the parent study

Patients from P2b Patients from QUEST

0,319 0,333 0,31 0,327 0,385 0,3570,278 0,277

0

0,50

1,00

1,50

2,00

2,50

Placebo/dupilumab

n = 111

Dupilumab/dupilumab

n = 421

Placebo/dupilumab

n = 107

Dupilumab/dupilumab

n = 396

Placebo/dupilumab

n = 517

Dupilumab/dupilumabn = 1013

Placebo/dupilumab

n = 425

Dupilumab/dupilumab

n = 816

Nu

mb

er

of

ex

ac

erb

ati

on

sin

th

ep

rio

rye

ar,

me

an

(SD

)

Unadjusted annualized exacerbation event rate during TRAVERSE

Patients from P2b Patients from QUEST

TRAVERSE

Week 0−48

TRAVERSE

Week 48−96

TRAVERSE

Week 0−48

TRAVERSE

Week 48−96

Proportions of patients

with no exacerbations (%) 78,4 80,8 80,4 79,5 77,6 79,8 88,9 89,3

Wechsler et al. ERS 2020, ms under review

Anti-IL4-Rα: TRAVERSE (Lungenfunktion) Dupilumab

28

PSBL2– 4– 6– 8– 10–12– 16– 20– 24– 28– 32– 36– 40– 44– 48– 0+ 2+ 4+ 8+ 12+ 24+ 48+ 72+ 84+ 96+0,00

0,05

0,10

0,15

0,20

0,25

0,30

0,35

0,40

0,45

0,50

Ch

an

ge

fro

mb

as

eli

ne

in p

re-b

ron

ch

od

ila

tor

FE

V1

(L),

mean

(±S

E)

Week

Placebo/dupilumab

Dupilumab/dupilumab

QUEST

52-week

treatment period

TRAVERSE

96-week

treatment period

EOS

-0,20

-0,15

-0,10

-0,05

0,00

0,05

0,10

0,15

0,20

0,25

PSBL 0 4 8 12 24 48 72 84 96

Ch

an

ge

fro

mP

SB

L in

blo

od

in

eo

sin

op

hil

s(G

iga

/L),

mean

(±S

E)

Week

IgE

29

Anti-IL4-Rα: TRAVERSE (Biomarker) Dupilumab

Wechsler et al. ERS 2020, ms under review

-500

-400

-300

-200

-100

0

100

PSBL 0 4 8 12 24 48 72 84 96

Ch

an

ge

fro

mP

SB

L in

to

tal

IgE

(IU

/mL

), m

ean

(±S

E)

Week

Exposed populations from P2bPlacebo/dupilumab

Dupilumab/dupilumab

Exposed populations from QUESTPlacebo/dupilumab

Dupilumab/dupilumab

All patients

Zusammenfassung

• 5−10 % der Asthmatiker haben ein schweres unkontrolliertes Asthma.

• Systemische Steroidgaben zur Dauertherapie dieser Patienten sind nur noch in begründeten

Ausnahmefällen indiziert.

• Biologika zur Therapie der Typ-2-Inflammation können die Asthmakontrolle bei Patienten mit

schwerem Asthma substanziell bessern.

30

Vielen Dank für Ihre Aufmerksamkeit!

Transparenzinformation

Diese CME wird Ihnen mit freundlicher Unterstützung von Sanofi-Aventis

auf cme.medlearning.de angeboten (€ 12.750,00).

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Documents

Biologika in der Therapie von schwerem Asthma: Wo stehen