PMID- 28948572
OWN - NLM
STAT- MEDLINE
DCOM- 20181119
LR  - 20181119
IS  - 1179-1950 (Electronic)
IS  - 0012-6667 (Linking)
VI  - 77
IP  - 16
DP  - 2017 Oct
TI  - Overlapping Effects of New Monoclonal Antibodies for Severe Asthma.
PG  - 1769-1787
LID - 10.1007/s40265-017-0810-5 [doi]
AB  - Among the monoclonal antibodies (mAbs) developed for severe asthma treatment, 
      three have already been marketed. Omalizumab was the first, more than 10 years 
      ago; today, mepolizumab and reslizumab are also available in the European Union 
      and the US. Omalizumab blocks free immunoglobulin E (IgE), mepolizumab and 
      reslizumab block an interleukin (IL-5). In the near future, dupilumab and 
      benralizumab are expected to emerge as two new alternatives. Benralizumab blocks 
      the receptor for IL-5 (IL5-Ralpha) and has a direct cytotoxic effect on eosinophils, 
      and dupilumab blocks the alpha-unit of the heterodimeric receptor for IL-4 and IL-13 
      (IL-4Ralpha); as a result, dupilumab can block both IL-4 and IL-13. The purpose of 
      this manuscript is to present the pathophysiology of some immunological aspects 
      of severe asthma, describe the adaptive and innate immunity arms as well as their 
      interrelations (stressing the subordination of the adaptive arm to the innate 
      arm), outline the pharmacologic effects of these mAbs, clarify the overlapping 
      effects of the different mAbs, and discuss the differences between mAbs based on 
      their target molecules. Based on the data presented, I propose omalizumab for 
      patients with an allergic phenotype regardless of their peripheral eosinophilic 
      count, and anti-IL-5 as an alternative in allergic patients with blood 
      eosinophilia in which omalizumab has failed; anti-IL5 for patients with an 
      eosinophilic phenotype and omalizumab as an alternative in patients in whom 
      anti-IL5 fails and IgE >/=30 IU/mL (compassionate use). Omalizumab is also proposed 
      for patients with severe chronic asthma allergic to seasonal allergens.
FAU - Domingo, Christian
AU  - Domingo C
AUID- ORCID: 0000-0001-8358-773X
AD  - Pulmonary Service, Hospital de Sabadell (Corporacio Sanitaria Parc Tauli), Parc 
      Tauli 1, 08208, Sabadell, Barcelona, Spain. cdomingo@tauli.cat.
AD  - Department of Medicine, Universitat Autonoma de Barcelona (UAB), Barcelona, 
      Spain. cdomingo@tauli.cat.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - New Zealand
TA  - Drugs
JT  - Drugs
JID - 7600076
RN  - 0 (Allergens)
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Interleukin-5)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Allergens/immunology
MH  - Anti-Asthmatic Agents/administration & dosage/*adverse 
      effects/chemistry/*pharmacology
MH  - Antibodies, Monoclonal, Humanized/administration & dosage/*adverse 
      effects/chemistry/*pharmacology
MH  - Asthma/*drug therapy/immunology
MH  - Cell Line
MH  - Chronic Disease
MH  - Eosinophils/metabolism
MH  - Humans
MH  - Immunoglobulin E/metabolism
MH  - Immunotherapy, Adoptive/methods
MH  - Interleukin-5/metabolism
EDAT- 2017/09/28 06:00
MHDA- 2018/11/20 06:00
CRDT- 2017/09/27 06:00
PHST- 2017/09/28 06:00 [pubmed]
PHST- 2018/11/20 06:00 [medline]
PHST- 2017/09/27 06:00 [entrez]
AID - 10.1007/s40265-017-0810-5 [pii]
AID - 10.1007/s40265-017-0810-5 [doi]
PST - ppublish
SO  - Drugs. 2017 Oct;77(16):1769-1787. doi: 10.1007/s40265-017-0810-5.