Secukinumab treatment shows no evidence of increased mycobacterium tuberculosis infections: Findings from in vitro, in vivo and clinical investigations
Introduction: While anti‐TNF treatments have been associated with increased incidence of acute tuberculosis (TB) and reactivation of latent tuberculosis infection (LTBI), anti‐IL‐17A treatment has no such known association to date. Here, we present in vitro, in vivo and clinical findings examining the effect of secukinumab (an anti-IL-17A antibody) on M. tuberculosis infection.
Materials and Methods: A mouse model study examined the effect of surrogate anti-IL‐17A, anti-IL‐17F, anti-TNFα or control antibodies on M. tuberculosis infection. A follow‐on in vitro study, using a human 3D microgranuloma model, examined the effect of adalimumab and secukinumab on human peripheral blood mononuclear cells infected with M. tuberculosis H37Rv. Finally, data was examined from 132 subjects (enrolled across 5 secukinumab phase 3 trials) who had a past history of pulmonary TB (n=25, negative by interferon-g release test, receiving no anti‐TB medication) or tested positive for latent TB (n=107, screened by interferon-g release test, receiving anti‐TB medication)
Results: In the acute mouse M. tuberculosis infection model, IL‐17 blockade did not alter body weight, pulmonary bacterial burden and lung histopathology. Anti‐TNFα antibody‐treated mice showed marked weight loss and increased pulmonary inflammation and bacterial burden. In the in vitro study, adalimumab treatment resulted in staining indicative of mycobacterial reactivation. In contrast, secukinumab treatment was comparable to the control indicating that the drug did not affect M. tuberculosis dormancy. Finally, in human phase 3 clinical trials with secukinumab, no cases of active TB were reported.
Conclusion: Preclinical and clinical investigations found no effect of anti‐IL17 blockade on M. tuberculosis infection.
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Dr. Chris Barker
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