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2018 ; 41
(5
): 489-509
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Potential Risks Related to Modulating Interleukin-13 and Interleukin-4
Signalling: A Systematic Review
#MMPMID29411337
Braddock M
; Hanania NA
; Sharafkhaneh A
; Colice G
; Carlsson M
Drug Saf
2018[May]; 41
(5
): 489-509
PMID29411337
show ga
INTRODUCTION: Interleukin-13 and interleukin-4 are type-II cytokines signalling
through the shared type II interleukin-4 receptor. As a result of their
structural similarity, interleukin-13 and interleukin-4 have overlapping
functions in the mediation of type-II-driven diseases and are, therefore,
promising targets of biologic drugs currently in development for the treatment of
such diseases, including asthma and atopic dermatitis. OBJECTIVE: This systematic
review was conducted to assess preclinical evidence of potential safety concerns
related to blockade of interleukin-13 alone or interleukin-13 and interleukin-4
in combination. METHODS: We specifically examined risks related to infection,
malignancy and the cardiovascular system. We systematically searched the BIOSIS,
MEDLINE and EMBASE databases to identify preclinical studies published between
January 2006 and October 2016 that addressed the effects of
interleukin-13/interleukin-4 blockade and modulation on the risk of infection,
malignancy and cardiovascular events. To provide a clinical context, we also
performed a search for clinical trials targeting the interleukin-13/interleukin-4
pathways. Relevant data from preclinical and clinical trials were abstracted and
presented descriptively. RESULTS: Aside from expected evidence that inhibition of
interleukin-13 and interleukin-4 impaired host responses to helminth infections,
we did not identify other preclinical evidence suggesting safety risks relating
to infection, malignancy or cardiovascular events. We found no evidence in
clinical trials suggesting serious safety concerns, i.e. increased risk for
infections, malignancy or cardiovascular events from therapeutic modulation of
the interleukin-13 pathway alone or the combined interleukin-13/interleukin-4
pathways. CONCLUSIONS: Although our findings are reassuring, long-term safety
assessments of biologics that target the interleukin-13/interleukin-4 pathways
currently in clinical development are needed.