Dal convegno "Novità diagnostico-terapeutiche in Allergologia e Immunologia Clinica" del 9 Novembre 2019, Torino

1. Responsabile
Programma trapianto
e gestione avanzata vie aeree
Università di Torino
Dipartimento di Scienze Mediche
Città della Salute e della Scienza di
Torino, Presidio Molinette
Dipartimento Cardiovascolare e
Toracico
S.C.U. PNEUMOLOGIA
Ambiti di utilizzo
della triplice
Paolo Solidoro

2. Responsabile
Programma trapianto
e gestione avanzata vie aeree
Università di Torino
Dipartimento di Scienze Mediche
Città della Salute e della Scienza di
Torino, Presidio Molinette
Dipartimento Cardiovascolare e
Toracico
S.C.U. PNEUMOLOGIA
Ambiti di utilizzo
della triplice
LABA/LAMA/ICS
In BPCO ed Asma
Paolo Solidoro

3. Conflict of interest statement
Speaker's hononaria from:
• Biofutura, Alfasigma, Astra Zeneca,
Boehringer Ingelheim, Pfizer, GSK,
Menarini, Novartis, Chiesi, Mundipharma,
Dompè, Guidotti and Malesci, Biotest,
ABC farmaceutici.
Consultant for training:
• Novartis, ABC Farmaceutici, Biotest.

4. For internal use only – strictly
confidential. Do not copy, detail or
4

6. the evidence suggests that FEV1 is a relatively poor correlate of symptoms
such as breathlessness and the impact of COPD on daily life
Particular attention is given to the newly developed instruments emerging in
response to recent regulatory guidelines for the development and use of
PROs in clinical trials.

7. Frequent exhacerbations 2 or moreHospitalization for exhacerbation y1
Both
Frequent exhacerbations: ECLIPSE
%patients

8. Rapporto tra riacutizzazione e funzione polmonare e
tra riacutizzazione e sopravvivenza nel paziente con
BPCO
All’aumentare del numero di riacutizzazioni (da 1-2 fino a 3 e oltre) si
osserva una perdita di funzione polmonare significativamente più rapida
e una minore probabilità di sopravvivenza.

9. For internal use only – strictly
confidential. Do not copy, detail or
9
Dyspnea is associated to hyperinflaction

11. ISOLDE study: effect of ICS on moderate/severe exacerbations
0,0
0,2
0,4
0,6
0,8
1,0
1,2
1,4
Placebo ICS*
Annualisedexacerbationrate
(medians) 25%, p=0.026
Burge et al BMJ 2001; 320:1297

12. Negli RCT, la terapia con ICS/LABA ha ridotto in modo significativo la frequenza di
riacutizzazioni BPCO
I risultati di due grandi meta-analisi Cochrane
1) Nannini et.al. Combined corticosteroid and long-acting B-agonist in one inhaler vs placebo for COPD (Review). Cochrane. 2013. (2) Nannini et.al. Combined
corticosteroid and long-acting B-agonist in one inhaler vs LABA for COPD (Review). Cochrane 2012 Tebelle originali in Appendix
FP/Sal, BUD/FOR (9 studi) (n=9921)
FP/Sal (5 studi) (n=6391)
BUD/FOR (4 studi) (n=2622)
FP/Sal, BUD/FOR (7 studi) (n=7495)
FP/Sal (3 studi) (n=4255)
BUD/FOR (4 studi) (n=3240)
BUD/FOR, budesonide/formoterolo; CI, intervallo di confidenza; FP, fluticasone propionato; ICS, corticosteroidi inalatori; LABA, long-acting beta2 agonist; Sal,
salmeterolo
Riduzione
~25%
Favours LABA

13. INSPIRE showed no significant difference in exacerbation rates
with salmeterol/fluticasone propionate vs tiotropium in at-risk patients
Tiotropium 18µg qd Salmeterol/fluticasone 50/500µg bid
0.0
0.5
1.0
1.5
2.0
HCU*exacerbationsmeannumberper
year
n=665
p=not significant
1.32 1.28
Overall exacerbations
Adapted from: Wedzicha JA, et al. Am J Respir Crit Care Med 2008; 177: 19–26.
*HCU: Health care utilization, defined as those that required treatment with oral corticosteroids and/or antibiotics or required hospitalization.
Ratio of exacerbation rates = 0.97
p=0.656; 95% CI: 0.84, 1.12
In patients with severe/very severe COPD and a history of exacerbation, there was no
significant difference in exacerbation rates with salmeterol/fluticasone vs tiotropium
Estimated annual exacerbation rate
n=658

14. INSPIRE showed no significant difference in exacerbation rates
with salmeterol/fluticasone propionate vs tiotropium in at-risk patients

16. Studio FLAME

17. FLAME: IND/GLY significantly delayed the time to first
exacerbation compared with SFC
b.i.d. twice daily; CI, confidence interval; GLY, glycopyrronium; IND, indacaterol; q.d., once daily; SFC, salmeterol-
fluticasone combination
Wedzicha et al. N Engl J Med. 2016 Jun 9;374(23):2222-34
0 6 12 19 26 32 38 5245
0
10
20
30
40
50
60
70
80
90
100
Probabilityofexacerbation(%)
Week
Hazard ratio, 0.84
(95% CI, 0.78-0.91) p<0.001
All
16% risk
reduction
Hazard ratio, 0.78
(95% CI, 0.70-0.86) p<0.001
Moderate or Severe
22% risk
reduction
Hazard ratio, 0.81
(95% CI, 0.66-1.00) p=0.046
Severe
19% risk
reduction
IND/GLY 110/50 μg q.d. (N=1675)
SFC 50/500 μg b.i.d. (N=1679)

18. NOT for promotional use - CONFIDENTIAL - do not
distribute
Triple 8 (TRIBUTE) – Study
Design/ Treatments
• Double-blind, Double-dummy, Randomized, Multinational &
multicentre, 2-arm parallel group, Active-controlled, 52-
week treatment.
1532 patients enrolled
from 146 sites in 17
Countries
Papi et al, Lancet 2018, http://dx.doi.org/10.1016/S0140-6736(18)30206-X

19. NOT for promotional use - CONFIDENTIAL - do not
distribute
Primary Endpoint:
moderate-to-severe exacerbations
• The low exacerbation rate compared to
the one before study randomization may
be due to a trial effect:
• Increased compliance to treatments
• More accurate identification of COPD
exacerbations by expert investigators
• No step-down treatment (all patients
came from mono or dual therapy)
which decreases the risk of
exacerbations
15.2%
reduction
Papi et al, Lancet 2018, http://dx.doi.org/10.1016/S0140-6736(18)30206-X

20. IMPACT: Significant reduction in moderate/severe
exacerbations with FF/UMEC/VI vs FF/VI and UMEC/VI
Note: The n reflects the number of patients included in each analysis from the ITT population. Patients were excluded if they had predefined data missing; this varied according to
the analysis. The ITT population comprised: 4,151 patients treated with FF/UMEC/VI, 4,134 patients treated with FF/VI and 2,070 patients treated with UMEC/VI.
Lipson DA, et al. N Engl J Med. 2018;378:1671–1680.
UMEC/VI
n = 2,069
Moderate/severeexacerbations
(annualrate)
FF/UMEC/VI
n = 4,145
FF/VI
n = 4,133
0,91
1,07
1,21
0
0,5
1
1,5
2 15% reduction
(95% CI: 10, 20)
p < 0.001
25% reduction
(95% CI: 19, 30)
p < 0.001
Moderate/severe exacerbations

21. Studio FLAME

22. IMPACT: Significant reduction in moderate/severe exacerbations in patients
with a history of exacerbations with FF/UMEC/VI vs FF/VI and UMEC/VI based on
exacerbation history
Note: The n reflects the number of patients included in each analysis from the ITT population. Patients were excluded if they had predefined data missing; this varied according to the
analysis. The ITT population comprised: 4,151 patients treated with FF/UMEC/VI, 4,134 patients treated with FF/VI and 2,070 patients treated with UMEC/VI.
Lipson DA, et al. N Engl J Med. 2018;378:1671–1680 (Supplementary Appendix).
UMEC/VI
n = 932
Moderate/severeexacerbations
inthelast12months
FF/UMEC/VI
n = 1,853
FF/VI
n = 1,911
0,86
1,08 1,08
0
0,5
1
1,5
2 20% reduction
(95% CI: 13, 28)
p < 0.001
21% reduction
(95% CI: 11, 29)
p < 0.001
UMEC/VI
n = 1,137
Moderate/severeexacerbations
inthelast12months
FF/UMEC/VI
n = 2,292
FF/VI
n = 2,222
0,94
1,06
1,32
0
0,5
1
1,5
2 11% reduction
(95% CI: 3, 18)
p = 0.008
28% reduction
(95% CI: 21, 35)
p < 0.001
1 moderate/severe exacerbation in the last 12
months
≥2 moderate/severe exacerbations in the last 12
months

23. Eosinophil activity during COPD
exacerbations
Eosinophilic
B, baseline; COPD, chronic obstructive pulmonary disease; E, exacerbations
1. Saetta M, et al. Am J Respir Crit Care Med 1994;150:1646–1652; 2. Bafadhel M, et al. Am J Respir Crit Care Med 2011;184:662–671
Airway eosinophils are expressed in greater proportions
in chronic bronchitis during exacerbations1
Eosinophilic-associated exacerbations
seen as a distinct cluster of patients2
100
80
60
40
20
0
E BE BE BE B
Percentage
Macrophages Neutrophils Eosinophils Lymphocytes
Bacterial
Viral
Pauciinflammatory

24. Sputum eosinophilia predicts response to
corticosteroids in COPD
1. Brightling CE et al. Lancet 2000; 356: 1480–5 , 2. Brightling CE et al. Thorax 2005; 60: 193–8
-0.05
0.00
0.05
0.10
0.15
0.20
0.25
*
Least to most
eosinophilic tertile
*p < 0.01
-0.05
0.00
0.05
0.10
0.15
0.20
**
Least to most
eosinophilic tertile
Post-bronchodilatorFEV1(L)
**p < 0.05
Mometasone2
Mean absolute increase in FEV1 after corticosteroids, compared with
placebo
Prednisolone1

25. 25
Conclusion: Peripheral blood
eosinophil counts can help identify
the presence or absence of
sputum eosinophilia in stable
COPD patients with a reasonable
degree of accuracy.

26. Blood Eosinophils Predict Response to
Inhaled Corticosteroids
Pavord Lancet Respir Med 2015

28. impact of ICS/LABA/LAMA combination vs.
LABA/LAMA combination on the risk of moderate or
severe AECOPD in COPD patients in agreement with
the blood eosinophil counts
Analisi condotta sulla base degli eosinofili ematici
Eur Respir J. 2018 Dec 13;52(6)

31. OPTIMO: ICS can be withdrawn in patients with
moderate COPD at low risk of exacerbation
31
Rossi A, et al. Respir Res 2014, 15: 77.
The feasibility of ICS withdrawal in patients with moderate COPD has been demonstrated in the
real-life setting, provided they receive regular treatment, mostly long-acting bronchodilators
74 71
0
20
40
60
80
100
%ofpatientsfreeof
exacerbationsafter6months
NO ICS ICS
p=0.35
Physician
decided to
withdraw ICS
<2
exacerbations
in previous
year
FEV1
>50% pred.
Percentage of patients without exacerbations
at the end of the study
(n=334) (n=482)

32. INSTEAD: a randomised switch trial of indacaterol versus
salmeterol/fluticasone in moderate COPD
FEV1
TDI
SGRQ
Effetto su FEV1, TDI e SGRQ
1.Rossi et al.Eur Respir J 2014; 44:
1548–1556
INSTEAD 2
• The INSTEAD study met its aims, demonstrating
that patients with moderate airflow limitation
and a history of no exacerbations can be
switched from SFC to indacaterol without any
loss in efficacy.

33. Magnussen H, et al. N Engl J Med 2014; 371: 1285–94.
WISDOM reported that ICS withdrawal is feasible in patients with
severe/very severe COPD and a history of exacerbations as long as
they remain on dual bronchodilation
Stepwise ICS withdrawal in severe but stable COPD is noninferior
to ICS continuation in terms of exacerbation risk
1243
1242
1059
1090
927
965
827
825
763
740
646
646
694
688
615
607
581
570
14
19
No. at risk
ICS
ICS withdrawal
0.6
0.4
0.2
0.0
0 6 12 18 24 30 36 42 48 54
ICS
ICS withdrawal
Estimatedprobability
Time to events (weeks)
0.1
0.3
0.5
Hazard ratio, 1.06 (95% CI: 0.94, 1.19)
p=0.35 by Wald’s chi-squaredtest
Moderate or severe COPD exacerbation

34. In the latest post-hoc analysis of WISDOM, a history of frequent exacerbations (≥2
exacerbations/year) plus a high eosinophil count of ≥300 cells/µL identifies a small
subgroup of patients at increased risk of exacerbation after complete ICS
withdrawal
1. Calverley PM, et al. Am J Respir Crit Care Med 2017: doi: 10.1164/rccm.201612-2525LE[Epub ahead of print];
2. Watz H, et al. Lancet Respir Med 2016; 4: 390–8.
Favours ICS
withdrawal
Favours ICS
0.5 1 2 4 8
Factors Number of patients Rate ratio
Total 841 1.07
Baseline eosinophils (<150/µL vs ≥150/µL)
<150/µL 403 1.02
≥150/µL 421 1.19
Baseline eosinophils (<300/µL vs ≥300/µL)
<300/µL 669 0.99
≥300/µL 155 1.75
Baseline eosinophils (<400/µL vs ≥400/µL)
<400/µL 738 1.00
≥400/µL 86 2.96
Baseline eosinophils (mutually exclusive
subgroups)
<150/µL 403 1.02
≥150/µL to <300/µL 266 0.99
≥300/µL to <400/µL 69 1.05
≥400/µL 86 2.96
The number of patients with COPD who experience a beneficial reduction in exacerbation risk
with ICS may be smaller than previously defined1,2
Rate ratios for moderate-to-severe exacerbations by baseline eosinophil count and ≥2 exacerbations/year

35. Numerous clinical trials, observational studies and meta-analyses have
reported a significantly increased risk of pneumonia in patients with
COPD treated with ICS
1. Horita N, et al. Cochrane Database Syst Rev 2017; 2: CD012066; 2. Global Initiative for Chronic Obstructive Lung Disease. Updated 2017.Available at:
http://goldcopd.org/gold-2017-global-strategy-diagnosis-management-prevention-copd/.
Comparison of pneumonia risk for LAMA/LABA vs ICS1
There is a high quality evidence from randomized controlled trials (RCTs) that ICS use is
associated with higher prevalence of pneumonia, amongst other adverse effects2

37. Tempo alla prima polmonite e tempo alla prima riacutizzazione con FF/VI vs VI
• Adapted from Crim C et al. Annals ATS. 2015;12:27–34, Crim C et al. Annals ATS. 2015 (Supplementary
Material)
FF/VI pneumonia (58 events)
FF/VI exacerbation (554 events) Vilanterol exacerbation (741 events)
Vilanterol pneumonia (28 events)
6 riacutizzazioni prevenute per ogni
polmonite causata
Pooled data from 2 replicate COPD exacerbation studies (total n=3255)

38. Mortalità associata alla polmonite con ICS+LABA vs LABA in monoterapia

39. NOT for promotional use - CONFIDENTIAL - do not
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Safety
The addition of extrafine BDP to LABA/LAMA does not
increase the risk of pneumonia
80% of pneumonia were confirmed by imaging
Papi et al, Lancet 2018, http://dx.doi.org/10.1016/S0140-6736(18)30206-X
Triple 8 (TRIBUTE) – Study Design/
Treatments

40. Long-term ICS use is associated with increases in HbA1c in
patients with COPD and comorbid type 2 diabetes, and with
diabetes onset and progression
1. Adapted from Price DB, et al. PLoS One 2016; 11: e0162903; 2. Suissa S, et al. Am J Med 2010; 123: 1001–6.
Adjusted rate ratio of diabetes incidence by ICS dose2Comparison of changes in HbA1c between ICS and
non-ICS cohorts1
Rateratio
Daily dose in fluticasone equivalents(μg)
125010007505002500 17501500 2000
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Adjusted difference (95% CI)
Ref: non-ICS
0.16 (0.05–0.27)
0.25 (0.10–0.40)
All COPD
(n=682 per cohort)
Change in HbA1c
Mild-to-moderate COPD
(n=443 per cohort)
Change in HbA1c
Decrease for ICS cohort Increase for ICS cohort
0.40−0.2−0.4−0.6−0.8 0.80.6 1−1 0.2

41. Long-term ICS use is associated with increases in HbA1c in
patients with COPD and comorbid type 2 diabetes, and with
diabetes onset and progression
1. Adapted from Price DB, et al. PLoS One 2016; 11: e0162903; 2. Suissa S, et al. Am J Med 2010; 123: 1001–6.
Adjusted rate ratio of diabetes incidence by ICS dose2Comparison of changes in HbA1c between ICS and
non-ICS cohorts1
Rateratio
Daily dose in fluticasone equivalents(μg)
125010007505002500 17501500 2000
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Adjusted difference (95% CI)
Ref: non-ICS
0.16 (0.05–0.27)
0.25 (0.10–0.40)
All COPD
(n=682 per cohort)
Change in HbA1c
Mild-to-moderate COPD
(n=443 per cohort)
Change in HbA1c
Decrease for ICS cohort Increase for ICS cohort
0.40−0.2−0.4−0.6−0.8 0.80.6 1−1 0.2

42. A dose-dependent increase in fracture risk has been reported with
long-term ICS use in COPD
Meta-analysis of RCTs (n=17513) and observational studies (n=69000) to assess risk of ICS-related fractures
Loke YK, et al. Thorax 2011; 66: 699–708.
Meta-analysis of odds of fracture with subcategories of inhaled corticosteroid exposure in
observationalstudies of patients with chronic obstructive pulmonary disease
Study or Subgroup Weight IV, Fixed, 95% CI IV, Fixed, 95% CI
Current or ever use vs no current or ever
use
Gonelli 2010 6.5% 1.26 (0.98 to 1.89)
Johannes 2007 4.9% 0.86 (0.59 to 1.25)
Lee 2004 11.4% 1.20 (0.94 to 1.54)
McEvoy 1998 1.6% 1.38 (0.71 to 2.69)
Pujades-Rodriguez 2007 34.2% 1.12 (0.97 to 1.29)
WEUSRTP 1127 2010 9.1% 1.10 (0.84 to 1.46)
WWE113669 2004 32.3% 1.42 (1.23 to 1.64)
Subtotal(95% CI) 100.0% 1.21 (1.12 to 1.32)
Heterogeneity: 𝜒2=9.53, df=6, (p=0.15);l2=37%
Test for overall effect: Z=4.56 (p<0.00001)
Subgroup: current use vs no current use
Johannes 2007 8.3% 0.86 (0.59 to 1.25)
Lee 2004 19.3% 1.20 (0.94 to 1.54)
McEvoy 1998 2.6% 1.38 (0.71 to 2.69)
WEUSRTP1127 2010 15.4% 1.10 (0.84 to 1.46)
WWE113669 2004 54.4% 1.42 (1.23 to 1.64)
Subtotal(95% CI) 100.0% 1.27 (1.14 to 1.41)
Heterogeneity: 𝜒2=7.66, df=4, (p=0.10);l2=48%
Test for overall effect: Z=4.28 (p<0.0001)
Subgroup: recent use vs no recent use
Johannes 2007 12.6% 1.02 (0.77 to 1.36)
Lee 2004 30.4% 1.14 (0.95 to 1.37)
WEUSRTP1127 2010 14.4% 1.36 (1.04 to 1.77)
WWE113669 2004 42.6% 1.35 (1.16 to 1.58)
Subtotal(95% CI) 100.0% 1.24 (1.12 to 1.37)
Heterogeneity: 𝜒2=4.25, df=3, (p=0.24);l2=29%.
Test for overall effect: Z=4.17 (p<0.0001). ICS Safe ICS Harmful
Odds ratio Odds ratio
0.5 0.7 1 1.5 2

43. Sospensione ICS (wisdom)
Magnussen H et al. N Engl J Med 2014; 371: 1285-1294
60ml

44. La sospensione degli ICS influisce
(p <0.001) sul FEV1 (-30 ml) e sulla
qualità di vita (+1.24 unità SGRQ),
anche se in modo non
clinicamente rilevante.

45. Nuovo paradigma?
il razionale per continuare la terapia con ICS
in pazienti che assumono broncodilatatori
ad azione prolungata dovrebbe essere
basato sul miglioramento sintomatico
attribuibile all’ICS piuttosto che sulla
prevenzione delle riacutizzazioni
Reilly, N Engl J Med 2014

46. NOT for promotional use - CONFIDENTIAL - do not
distribute
Papi et al, Lancet 2018, http://dx.doi.org/10.1016/S0140-6736(18)30206-X

47. Confidential - For GSK Internal Training Only. These Materials May Not be Shown to Customers.47
HRQoL (SGRQ)
MCID = –4
Miglioramento della HRQoL (SGRQ) e impatto sui singoli domini con
FF/UMEC/VI vs FF/VI e vs UMEC/VI
Lipson et al, N Engl J Med. 2018 Aug 9;379(6):592-593
IMPACT

48. NOT for promotional use - CONFIDENTIAL - do not
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49. NOT for promotional use - CONFIDENTIAL - do not
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50. NOT for promotional use - CONFIDENTIAL - do not
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51. NOT for promotional use - CONFIDENTIAL - do not
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52. NOT for promotional use - CONFIDENTIAL - do not
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53. NOT for promotional use - CONFIDENTIAL - do not
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54. Arch Bronconeumol, 2017;53(6):324–335

55. Arch Bronconeumol, 2017;53(6):324–335

56. Treatment of stable COPD
© 2017 Global Initiative for Chronic Obstructive Lung Disease
© 2019 Global Initiative for Chronic Obstructive Lung Disease
Definition of abbreviations: eos: blood eosinophil count in cells per microliter; mMRC: modified Medical Research
Council dyspnea questionnaire; CAT™: COPD Assessment Test™.

57. © 2017 Global Initiative for Chronic Obstructive Lung Disease
© 2019 Global Initiative for Chronic Obstructive Lung Disease

58. * Off-label; data only with budesonide-formoterol (bud-form)
† Off-label; separate or combination ICS and SABA inhalers
PREFERRED
CONTROLLER
to prevent exacerbations
and control symptoms
Other
controller options
Other
reliever option
PREFERRED
RELIEVER
STEP 2
Daily low dose inhaled corticosteroid (ICS),
or as-needed low dose ICS-formoterol *
STEP 3
Low dose
ICS-LABA
STEP 4
Medium dose
ICS-LABA
Leukotriene receptor antagonist (LTRA), or
low dose ICS taken whenever SABA taken †
As-needed low dose ICS-formoterol *
As-needed short-acting β2 -agonist (SABA)
Medium dose
ICS, or low dose
ICS+LTRA #
High dose
ICS, add-on
tiotropium, or
add-on LTRA #
Add low dose
OCS, but
consider
side-effects
As-needed low dose ICS-formoterol ‡
Box 3-5A
Adults & adolescents 12+ years
Personalized asthma management:
Assess, Adjust, Review response
Asthma medication options:
Adjust treatment up and down for
individual patient needs
STEP 5
High dose
ICS-LABA
Refer for
phenotypic
assessment
± add-on
therapy,
e.g.tiotropium,
anti-IgE,
anti-IL5/5R,
anti-IL4R
Symptoms
Exacerbations
Side-effects
Lung function
Patient satisfaction
Confirmation of diagnosis if necessary
Symptom control & modifiable
risk factors (including lung function)
Comorbidities
Inhaler technique & adherence
Patient goals
Treatment of modifiable risk
factors & comorbidities
Non-pharmacological strategies
Education & skills training
Asthma medications
1© Global Initiative for Asthma, www.ginasthma.org
STEP 1
As-needed
low dose
ICS-formoterol *
Low dose ICS
taken whenever
SABA is taken †
‡ Low-dose ICS-form is the reliever for patients prescribed
bud-form or BDP-form maintenance and reliever therapy
# Consider adding HDM SLIT for sensitized patients with
allergic rhinitis and FEV >70% predicted

67. 67

68. * Off-label; data only with budesonide-formoterol (bud-form)
† Off-label; separate or combination ICS and SABA inhalers
PREFERRED
CONTROLLER
to prevent exacerbations
and control symptoms
Other
controller options
Other
reliever option
PREFERRED
RELIEVER
STEP 2
Daily low dose inhaled corticosteroid (ICS),
or as-needed low dose ICS-formoterol *
STEP 3
Low dose
ICS-LABA
STEP 4
Medium dose
ICS-LABA
Leukotriene receptor antagonist (LTRA), or
low dose ICS taken whenever SABA taken †
As-needed low dose ICS-formoterol *
As-needed short-acting β2 -agonist (SABA)
Medium dose
ICS, or low dose
ICS+LTRA #
High dose
ICS, add-on
tiotropium, or
add-on LTRA #
Add low dose
OCS, but
consider
side-effects
As-needed low dose ICS-formoterol ‡
Box 3-5A
Adults & adolescents 12+ years
Personalized asthma management:
Assess, Adjust, Review response
Asthma medication options:
Adjust treatment up and down for
individual patient needs
STEP 5
High dose
ICS-LABA
Refer for
phenotypic
assessment
± add-on
therapy,
e.g.tiotropium,
anti-IgE,
anti-IL5/5R,
anti-IL4R
Symptoms
Exacerbations
Side-effects
Lung function
Patient satisfaction
Confirmation of diagnosis if necessary
Symptom control & modifiable
risk factors (including lung function)
Comorbidities
Inhaler technique & adherence
Patient goals
Treatment of modifiable risk
factors & comorbidities
Non-pharmacological strategies
Education & skills training
Asthma medications
1© Global Initiative for Asthma, www.ginasthma.org
STEP 1
As-needed
low dose
ICS-formoterol *
Low dose ICS
taken whenever
SABA is taken †
‡ Low-dose ICS-form is the reliever for patients prescribed
bud-form or BDP-form maintenance and reliever therapy
# Consider adding HDM SLIT for sensitized patients with
allergic rhinitis and FEV >70% predicted

69. Responsabile
Programma trapianto
e gestione avanzata vie aeree
Università di Torino
Dipartimento di Scienze Mediche
Città della Salute e della Scienza di
Torino, Presidio Molinette
Dipartimento Cardiovascolare e
Toracico
S.C.U. PNEUMOLOGIA
Ambiti di utilizzo
della triplice
Paolo Solidoro