Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections
Journal
Clinical and Translational Immunology
Journal Volume
6
Journal Issue
8
Pages
e152
Date Issued
2017
Author(s)
Kamm?ller M.
Griffiths C.E.M.
Kapoor N.
Kolattukudy P.E.
Brees D.
Chibout S.-D.
Safi J.
Jr.
Fox T.
Abstract
Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re-assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis. No cases of TB were observed after 1 year. Importantly, in subjects with a history of pulmonary TB (but negative for interferon-γ release and receiving no anti-TB medication) or positive for latent TB (screened by interferon-γ release assay and receiving anti-TB medication), no cases of active TB were reported. Moreover, an in vitro study examined the effect of the anti-tumor necrosis factor-α (TNFα) antibody adalimumab and secukinumab on dormant M. tuberculosis H37Rv in a novel human three-dimensional microgranuloma model. Auramine-O, Nile red staining and rifampicin resistance of M. tuberculosis were measured. In vitro, anti-TNFα treatment showed increased staining for Auramine-O, decreased Nile red staining and decreased rifampicin resistance, indicative of mycobacterial reactivation. In contrast, secukinumab treatment was comparable to control indicating a lack of effect on M. tuberculosis dormancy. To date, clinical and preclinical investigations with secukinumab found no evidence of increased M. tuberculosis infections. ? The Author(s) 2017.
SDGs
Other Subjects
adalimumab; alanine aminotransferase; aspartate aminotransferase; bilirubin; gamma interferon; isoniazid; liver enzyme; rifampicin; secukinumab; alanine aminotransferase blood level; antibiotic resistance; Article; aspartate aminotransferase blood level; bilirubin blood level; chemoprophylaxis; colony forming unit; combination drug therapy; comparative study; controlled study; double blind procedure; drug effect; drug safety; enzyme blood level; human; human cell; hypertransaminasemia; in vitro study; incidence; interferon gamma release assay; latent tuberculosis; lung tuberculosis; major clinical study; medical history; observational study; phase 3 clinical trial (topic); priority journal; Psoriasis Area and Severity Index; psoriasis vulgaris; randomized controlled trial (topic); recurrent infection; retrospective study; side effect; staining
Publisher
Nature Publishing Group
Type
journal article