PMID- 26471366
OWN - NLM
STAT- MEDLINE
DCOM- 20160502
LR  - 20220311
IS  - 1474-1784 (Electronic)
IS  - 1474-1776 (Linking)
VI  - 15
IP  - 1
DP  - 2016 Jan
TI  - Targeting key proximal drivers of type 2 inflammation in disease.
PG  - 35-50
LID - 10.1038/nrd4624 [doi]
AB  - Systemic type 2 inflammation encompassing T helper 2 (TH2)-type responses is 
      emerging as a unifying feature of both classically defined allergic diseases, 
      such as asthma, and a range of other inflammatory diseases. Rather than reducing 
      inflammation with broad-acting immunosuppressants or narrowly targeting 
      downstream products of the TH2 pathway, such as immunoglobulin E (IgE), efforts 
      to target the key proximal type 2 cytokines - interleukin-4 (IL-4), IL-5 and 
      IL-13 - represent a promising strategy to achieve therapeutic benefit across 
      multiple diseases. After several initial disappointing clinical results with 
      therapies targeting IL-4, IL-5 or IL-13 in asthma, applying a personalized 
      approach achieved therapeutic benefit in an asthma subtype exhibiting an 
      'allergic' phenotype. More recently, efficacy was extended into a broad 
      population of people with asthma. This argues that the Type 2 inflammation is 
      broadly relevant across the severe asthma population if the key upstream drivers 
      are properly blocked. Moreover, the simultaneous inhibition of IL-4 and IL-13 has 
      shown significant clinical activity in diseases that are often co-morbid with 
      asthma - atopic dermatitis and chronic sinusitis with nasal polyps - supporting 
      the hypothesis that targeting a central 'driver pathway' could benefit multiple 
      allergic diseases.
FAU - Gandhi, Namita A
AU  - Gandhi NA
AD  - Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
FAU - Bennett, Brandy L
AU  - Bennett BL
AD  - Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
FAU - Graham, Neil M H
AU  - Graham NM
AD  - Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
FAU - Pirozzi, Gianluca
AU  - Pirozzi G
AD  - Research and Development, Sanofi, Bridgewater, New Jersey 08807, USA.
FAU - Stahl, Neil
AU  - Stahl N
AD  - Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
FAU - Yancopoulos, George D
AU  - Yancopoulos GD
AD  - Regeneron Pharmaceuticals, Tarrytown, New York 10591, USA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20151016
PL  - England
TA  - Nat Rev Drug Discov
JT  - Nature reviews. Drug discovery
JID - 101124171
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-5)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Humans
MH  - Inflammation/*drug therapy/*immunology
MH  - Interleukin-13/antagonists & inhibitors/immunology
MH  - Interleukin-4/antagonists & inhibitors/immunology
MH  - Interleukin-5/antagonists & inhibitors/immunology
MH  - Models, Immunological
MH  - Molecular Targeted Therapy/*methods
MH  - T-Lymphocytes, Helper-Inducer/*drug effects/*immunology
EDAT- 2015/10/17 06:00
MHDA- 2016/05/03 06:00
CRDT- 2015/10/17 06:00
PHST- 2015/10/17 06:00 [entrez]
PHST- 2015/10/17 06:00 [pubmed]
PHST- 2016/05/03 06:00 [medline]
AID - nrd4624 [pii]
AID - 10.1038/nrd4624 [doi]
PST - ppublish
SO  - Nat Rev Drug Discov. 2016 Jan;15(1):35-50. doi: 10.1038/nrd4624. Epub 2015 Oct 
      16.