This document discusses mepolizumab, an anti-IL5 biological agent used to treat severe eosinophilic asthma. It provides background on interleukin 5 (IL-5) and its role in the differentiation, survival and function of eosinophils. The document also discusses the clinical efficacy of mepolizumab in treating bronchial asthma, eosinophilic granulomatosis with polyangiitis (EGPA), and issues to be solved regarding its effects and consequences on clinical outcomes based on personal experience treating patients.

1. Meccanismo di Azione ed
Indicazioni di Mepolizumab
AOU Careggi - Firenze
SOD Immunoallergologia
andrea.matucci@unifi.it
Andrea Matucci

2. BIOLOGICAL
AGENTS
ASTHMA TREATMENTS

3. GINA Treatment Guidelines of Asthma
3
ICS = inhaled corticosteroid; IgE = immunoglobulin E; IL5 = interleukin 5; LABA = long-acting beta2-agonist; LTRA = leukotriene receptor
antagonist; OCS = oral corticosteroid; SABA = short-acting beta2-agonist.
1. Global Initiative For Asthma (GINA). Global strategy for asthma management and prevention. Updated 2017. http://ginasthma.org/2017-
gina-report-global-strategy-for-asthma-management-and-prevention//. Accessed February 2017; 2. Chanez P et al. J Allergy Clin Immunol.
2007;119:1337-1348.
Preferred
controller
choice
Consider low-
dose ICS
Low-dose ICS
Step 1 Step 2
Step 3
Step 4
Step 5
Reliever
Other
options
LTRA
Low-dose theophyllinea
Low-dose
ICS/LABAb
Med/High
ICS/LABA
Refer for add-on
treatment
(eg. tiotropium
anti-IgE, anti-IL5)a
Med/High ICS
Low-dose ICS +
LTRA (or +
theophylline) a
Add tiotropiuma,c
High-dose ICS +
LTRA (or
+theophylline)a
Add low-dose
OCS
As needed SABA
As needed SABA or
low-dose ICS/formoterol

4. Available Biological Strategies for Severe As

5. Why should we use an anti-IL5 strategy ?

6. (CHEST 2017)

7. Asthma Severity,
(Risk of Exacerbations,
Emergency visits and
Hospitalizations)
Lung Function
- Bousquet J. et al. NEJM 1990;323:1033-9
- Price DB; et al. Lancet Resp Med 2015; 3:849-
- Louis R., et al. AJRCM 2000;161:9-16
- McGrath KW., et al. AJRCM 2012;185:612-9

8. MIGRAZIONE POLMONARE DEGLI EOSINOFILI
Eotassina
Romagnani S., Matucci A., Rossi O. – Asma Bronchiale SEE Ed. 2004

9. IL-5: TARGET FOR BIOLOGICAL AGENTS
IL-5R (a;b) IL-5; GM-CSF;IL-3
Differentiation, survival and functions of Eosinophils may be also
mediated by IL-3 and GM-CSF.
Matucci A.; Vultaggio A. Master in Allergologia; Napoli 2015

10. The Clinical Efficacy of Mepolizumab
in Bronchial Asthma and EGPA

11. (2017)

12. (2017)

13. (2017)

15. Asthma as starting condition for
Churg-Strauss Syndrome
PHASE 1
(ASTHMA/ATOPY)
PHASE 2
(IPEREOSINOPH.)
PHASE 3
(VASCULITIS)
Overt disease with
multiple organ
involvement
Severe
persistent Astma

19. Are There Some Issues To Be Solved
on Mepolizumab Effects ?
And
Are There some Consequences on
Clinical Outcomes ?
Questions

20. -100% -55%
-52%
Median decrease

21. Mepolizumab (750 mg/iv): Sindrome di Gleich
ECP
(mg/mL)
Data
111 30/6/2008
37 5/5/2011
16 3/6/2011
Riduzione dose giornaliera steroidi
Matucci A., et al. Frontiers Immunol (2018)

22. Allergens Virus
YYY
Capture allergens
> APC function (T cell activation)
mpaired IFN production
(> risk of viral infection)
DC
Th2 B
Mc
Eos
Eos
Eos
Eos
ILC2
- Release of preformed
mediators (acute phase)
- Improve APC function
(secondary response)
TLSP
IL-25
IL-33
FINAL
EFFECTOR
FUNCTION OF
EOSINOPHILS
DRIVING ROLE
OF IgE
ASMC
- Hypertrophy; Hyperplasia;
contraction.
- Cytokines release
IgE
IgE
IgE
IgE
Matucci A., Vultaggio A., Maggi E., et al. (Respir Research 2018)

23. IL-5: TARGET FOR BIOLOGICAL AGENTS
IL-5R (a;b) IL-5; GM-CSF;IL-3
Differentiation, survival and functions of Eosinophils may be also
mediated by IL-3 and GM-CSF.
Matucci A.; Vultaggio A. Master in Allergologia; Napoli 2015

25. Personal Experience with Mepolizumab

26. 121 Churg-Strauss patients(≥4 ARA criteria)
M/F: 41/80; age at diagnosis 50,1 ± 13,4 yrs
History of Asthma: 9,2 yrs (3-25 yrs)
Pheriph. Eosinophils at diagnosis: 35.6 ± 14.3
CHURG-STRAUSS SYNDROME (CASE SERIES)
Personal data -
Asthma Nasal
polyps
Chest Atopy Pheripheral
Neural S.
Kidney Joints Skin ANCA+

27. SNC
Heart
Kidney
Joints
SNP
Churg-Strauss patients Severe Asthma patientsAsthma patients
- High dose of steroids (pulse)
- Immunosoppressor (CKF)
Responder patients
No Responder patients (10,3%)
79 Patients with CSS patients
71
8
- Inhalant steroids
- High dose of oral steroids
- Immunosoppressor
(CoA, MTX, AZA)
Personal unpublished data