Active tuberculosis in psoriasis patients treated with TNF antagonists: a French nationwide retrospective study

Abstract

This study shows tuberculosis in patients treated with TNF antagonists still occurs despite adherence to tuberculosis prevention guidelines. Prophylactic measures do not fully prevent the occurrence of tuberculosis. Rapid initiation of effective anti-tuberculosis treatment is important even in patients with negative mycobacteriological examination presenting with suggestive symptoms and organ involvement.

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

“…36 Unlike the equivocal role of IL-17A in host resistance to M. tuberculosis infections, [18][19][20][21][22] the importance of tumor necrosis factor-α (TNFα) in immunity to this intracellular pathogen is well established, as documented clinically by the association of anti-TNFα therapies with reactivation of LTBIs, in psoriasis and rheumatoid arthritis indications. [9][10][11][12][13] In a recent investigation we compared side by side the effects of anti-IL-17A, anti-IL-17F or TNFα-neutralizing surrogate antibodies in a murine M. tuberculosis H37Rv infection model, and confirmed the importance of TNFα in immunity to M. tuberculosis infection, in contrast to the anti-IL-17 pathway. 37 To further explore any associations of secukinumab with reactivation of LTBIs, we have retrospectively re-evaluated pooled phase 3 clinical trials in subjects with moderate to severe plaque psoriasis, who had a history of pulmonary TB or tested positive for latent TB at screening, and received secukinumab for 1 year.…”

“…Anti-TNFα antibody treatment can lead to reactivation of latent M. tuberculosis infections. [9][10][11][12][13] Here we tested whether M. tuberculosis in cells of the in vitro microgranuloma can be reactivated by anti-TNFα adalimumab antibody treatment. Once the microgranuloma structures were formed in vitro, adalimumab was added to the media at 10 ng ml − 1 .…”

“…The role of TNFα is documented clinically by the association of anti‐TNFα therapies with reactivation of LTBIs in psoriasis and rheumatoid indications 9 , 10 , 11 , 12 , 13 . TNFα has an important role in balancing cell survival, apoptosis and programmed necrosis in M. tuberculosis infections 13 , 52 .…”

“…By blocking critical mediators of innate and adaptive immunity, biotherapeutics may carry a risk of increased opportunistic infections 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 . It has been shown that IL‐17A has a role in immune defense in mucocutaneous barrier tissues, 14 , 15 , 16 in particular to extracellular fungi such as Candida albicans.…”

“…[1][2][3][4] By blocking critical mediators of innate and adaptive immunity, biotherapeutics may carry a risk of increased opportunistic infections. [5][6][7][8][9][10][11][12][13] It has been shown that IL-17A has a role in immune defense in mucocutaneous barrier tissues, [14][15][16] in particular to extracellular fungi such as Candida albicans. [6][7][8] In psoriasis patients, a 52week treatment with secukinumab showed a dose-dependent but overall low incidence of transient, mild to moderate mucosal and cutaneous candidiasis, 17 which is controllable by standard therapy and did not lead to any discontinuations in phase 2 and 3 clinical studies in patients with moderate to severe plaque psoriasis.…”