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

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.

Long‐term safety of brodalumab in Japanese patients with plaque psoriasis: An open‐label extension study

“…By blocking critical mediators of adaptive and innate immunity, biotherapeutics may carry a risk of increased opportunistic infections. IL‐17A has a role in immune defense in mucocutaneous barrier tissues and may play a role during Mycobacterium tuberculosis infection 19 …”

Safety of biologics in psoriasis

“…A meta‐analysis of four clinical trials of ustekinumab revealed that the risk of TB with ustekinumab is lower than that observed with anti‐TNF‐α‐therapy . Additionally, Kammuller et al . reported that clinical investigations with secukinumab have shown no evidence of TB infection.…”

“…A meta-analysis of four clinical trials of ustekinumab revealed that the risk of TB with ustekinumab is lower than that observed with anti-TNF-a-therapy. 21 Additionally, Kammuller et al 22 reported that clinical investigations with secukinumab have shown no evidence of TB infection. Although the risks of LTBI reactivation with IL-12/ 23p40 antibody and IL-17 inhibitors differ from those with TNFa inhibitors, established guidelines in the USA, 23 Europe 24 and Japan 25 recommend screening prior to initiation of any biologics for psoriasis.…”

Update on recommendations for eligibility of government subsidization of biologic disease‐modifying antirheumatic drugs for the treatment of axial spondyloarthritis in Singapore

“…However, members of the TFP felt that specific clinical considerations in the local context need to be acknowledged, such as higher exposure to tuberculosis. A recent review of pool safety data from trials involving secukinumab did not show an increased risk of tuberculosis infection . Alongside growing experience of the use of secukinumab in Singapore, having an additional first‐line option available is important.…”

“…A recent review of pool safety data from trials involving secukinumab did not show an increased risk of tuberculosis infection. 36 Alongside growing experience of the use of secukinumab in Singapore, having an additional first-line option available is…”