Annals of the rheumatic diseases
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Randomized Controlled Trial
Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation.
Interleukin (IL)-17A has emerged as pivotal in driving tissue pathology in immune-mediated inflammatory diseases. The role of IL-17F, sharing 50% sequence homology and overlapping biological function, remains less clear. We hypothesised that IL-17F, together with IL-17A, contributes to chronic tissue inflammation, and that dual neutralisation may lead to more profound suppression of inflammation than inhibition of IL-17A alone. ⋯ These data support IL-17F as a key driver of human chronic tissue inflammation and the rationale for dual neutralisation of IL-17A and IL-17F in PsA and related conditions.
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Leflunomide is known to be embryotoxic and teratogenic in rodents. However, there is less evidence in humans. We quantified the risk of major congenital malformation (MCM), prematurity, low birth weight (LBW) and spontaneous abortion associated with leflunomide exposure during pregnancy in humans. ⋯ Maternal exposure to leflunomide during pregnancy was not associated with statistically significant increased risk of MCMs, prematurity, LBW or spontaneous abortions. However, given that relatively few women were exposed to leflunomide during pregnancy in this cohort, caution remains warranted.
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To characterise the clinical features, immune manifestations and molecular mechanisms in a recently described autoinflammatory disease caused by mutations in TRNT1, a tRNA processing enzyme, and to explore the use of cytokine inhibitors in suppressing the inflammatory phenotype. ⋯ Mutations of TRNT1 lead to a severe and often fatal syndrome, linking protein homeostasis and autoinflammation. Molecular diagnosis in early life will be crucial for initiating anti-TNF therapy, which might prevent some of the severe disease consequences.