Background: Tuberculosis has a major global impact. Immunocompetent hosts usually control this disease, resulting in an asymptomatic latent tuberculosis infection (LTBI). Because TNF inhibitors increase the risk of tuberculosis reactivation, current guidelines recommend tuberculosis screening before starting any biologic drug, and chemoprophylaxis if LTBI is diagnosed. Available evidence from clinical trials and real-world studies suggests that IL-17 and IL-23 inhibitors do not increase the risk of tuberculosis reactivation.
Objective: To evaluate psoriasis patients with treated or untreated newly diagnosed LTBI who received IL-17 and IL-23 inhibitors and the tolerability/safety of tuberculosis chemoprophylaxis.
Methods: This is a retrospective, observational, multinational study from a series of 14 dermatology centres based in Portugal, Spain, Italy, Greece and Brazil, which included adult patients with moderate-to-severe chronic plaque psoriasis and newly diagnosed LTBI who were treated with IL-23 or IL-17 inhibitors between January 2015 and March 2022. LTBI was diagnosed in the case of tuberculin skin test and/or interferon gamma release assay positivity, according to local guideline, prior to initiating IL-23 or IL-17 inhibitor. Patients with prior diagnosis of LTBI (treated or untreated) or treated active infection were excluded.
Results: A total of 405 patients were included; complete/incomplete/no chemoprophylaxis was administered in 62.2, 10.1 and 27.7% of patients, respectively. The main reason for not receiving or interrupting chemoprophylaxis was perceived heightened risk of liver toxicity and hepatotoxicity, respectively. The mean duration of biological treatment was 32.87 ± 20.95 months, and only one case of active tuberculosis infection (ATBI) was observed, after 14 months of treatment with ixekizumab. The proportion of ATBI associated with ixekizumab was 1.64% [95% confidence interval (CI): 0-5.43%] and 0% for all other agents and 0.46% (95% CI 0-1.06%) and 0% for IL-17 and IL-23 inhibitors, respectively (not statistically significant).
Conclusions: The risk of tuberculosis reactivation in patients with psoriasis and LTBI does not seem to increase with IL-17 or IL-23 inhibitors. IL-17 or IL-23 inhibitors should be preferred over TNF antagonists when concerns regarding tuberculosis reactivation exists. In patients with LTBI considered at high risk for developing complications related to chemoprophylaxis, this preventive strategy may be waived before initiating treatment with IL-17 inhibitors and especially IL-23 inhibitors.
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http://dx.doi.org/10.1007/s40257-024-00845-4 | DOI Listing |
Br J Dermatol
December 2024
Department of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Background: No currently approved treatment for pediatric plaque psoriasis selectively targets interleukin (IL)-23. In adults, guselkumab (a selective IL-23 inhibitor targeting the p19 subunit) demonstrated substantial efficacy with a favorable safety profile in treating moderate-to-severe plaque psoriasis.
Objective: PROTOSTAR (NCT03451851) evaluated the efficacy and safety of guselkumab in pediatric patients with moderate-to-severe plaque psoriasis.
Lancet
December 2024
Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt, Germany.
Background: Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis.
View Article and Find Full Text PDFJ Dermatol
December 2024
Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Generalized pustular psoriasis (GPP) is a severe autoinflammatory keratinization disease (AiKD) characterized by acute flares of widespread sterile pustules and high fever. GPP is potentially life-threatening. Recently clarified genetic predisposing factors for GPP suggest that the excessive activation of innate immune pathways in the skin, including of interleukin (IL)-1 and IL-36 signaling, plays a significant role in the GPP pathogenesis.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
Background: The phosphodiesterase 4 (PDE4) inhibitor apremilast downregulates the production of IL-23 and other pro-inflammatory cytokines involved in the pathogenesis of psoriatic arthritis (PsA).
Aim: To investigate the effects of apremilast on the production of cytokines by peripheral blood monocyte-derived macrophages, innate-like lymphocyte cells (ILCs), mucosal-associated invariant T (MAIT) cells, γδ T cells, natural killer (NK) cells, and NKT-like cells from patients with PsA manifesting different clinical responses to the treatment.
Methods: Peripheral blood samples were obtained from patients with PsA at baseline and after 1 and 4 months of apremilast therapy (n = 23) and 20 controls with osteoarthritis.
is a leading cause of healthcare associated infection and an unacceptably high proportion of patients with infection die despite conventional antibiotic treatment. Host-directed immunotherapy has been proposed as an ideal treatment modality for infection to mitigate the underlying toxin-mediated pathogenic immune response while sparing protective gut microbes. Interleukin-23 monoclonal antibody inhibitors are used extensively to control pro-inflammatory Th17 immune pathways in psoriasis and inflammatory bowel disease that are similarly important during infection.
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