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Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

Kammueller, Michael and Tsai, Tsen-Fang and Griffiths, Christopher EM and Kapoor, Nidhi and Kolattukudy, Pappachan E and Brees, Dominique and Chibout, Salah-Dine and Safi Jr., Jorge and Fox, Todd (2017) Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections. Clinical and translational immunology, 6 (8). e152. ISSN 2050-0068

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.

Item Type: Article
Date Deposited: 09 Sep 2017 00:45
Last Modified: 09 Sep 2017 00:45
URI: https://oak.novartis.com/id/eprint/32363

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