ABSTRACT
INTRODUCTION: Ankylosing spondylitis, also known as radiographic axial spondyloarthritis, is a complex, immune-mediated inflammatory disorder most commonly involving the spine including the sacroiliac joints. AREAS COVERED: Complex pathogenesis of axial spondyloarthritis involving genetic, environmental, and both innate and adaptive immune systems. Treatment options for ankylosing spondylitis. Pharmacologic properties, efficacy, and safety of tofacitinib, a JAK inhibitor. Data regarding efficacy of approved JAK inhibitors in the treatment of ankylosing spondylitis, including tofacitinib, upadacitinib, and filgotinib. EXPERT OPINION: Current treatment options of ankylosing spondylitis include NSAIDs, TNFi, and IL-17i. JAK inhibitors present a new class of therapy that has shown efficacy in the treatment of active ankylosing spondylitis in adults. While it has not been directly compared to alternative therapies, tofacitinib has been shown to be effective in both phase II and phase III trials for the treatment of ankylosing spondylitis. While these trials did not show any significant difference from placebo in terms of safety, the ORAL Surveillance study showed tofacitinib to be inferior to TNFi when comparing adverse events. Thus, tofacitinib presents a viable treatment option for the management of AS, however shared decision-making regarding risks and benefits will be important.
Subject(s)
Janus Kinase Inhibitors , Spondylitis, Ankylosing , Adult , Humans , Janus Kinase Inhibitors/therapeutic use , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Spondylitis, Ankylosing/drug therapyABSTRACT
INTRODUCTION: Psoriatic arthritis (PsA) is a complex, polygenic immune-mediated disease with varying clinical presentations involving the skin, nails, entheses, and axial/peripheral skeleton. AREAS COVERED: Pathophysiology of PsA with special focus on IL-23/IL-17 axis. Novel classes of targeted therapies for PsA. Pharmacologic properties, efficacy and safety of guselkumab, the only FDA approved agent from IL-23p19 inhibitor class. Data regarding other IL-23 inhibitors (Ustekinumab - an IL-12/IL-23p40 inhibitor, Risankizumab and Tildrakizumab - both IL23p19 inhibitors), in the treatment of PsA. EXPERT OPINION: There are seven classes of FDA-approved therapies for the treatment of PsA. IL-23p19 inhibitors are the newest class of medications that has shown efficacy and reasonable safety profile in the treatment of PsA in phase 2 and phase 3 studies; Guselkumab is the only FDA-approved biologic for PsA within this class . While no head-to-head studies of IL-23p19 inhibitors and other PsA targeted therapies are available, the efficacy of these agents on musculoskeletal system appears to be comparable to TNF-inhibitors (TNFi), and the efficacy on the skin appears to be comparable, or modestly superior to the IL-17 inhibitors (IL-17i). With a superior safety profile compared to TNFi and IL-17i, IL-23p19 inhibitors have the potential to become a first-line biologic in the treatment of PsA.
Subject(s)
Arthritis, Psoriatic , Arthritis, Psoriatic/drug therapy , Humans , Interleukin-23 , Skin , Tumor Necrosis Factor Inhibitors , Ustekinumab/therapeutic useABSTRACT
Researchers have observed that a sialic acid (Sia)-supplemented neonatal diet leads to improved cognition in weanling piglets. However, whether cognitive improvement appears with different physiological backgrounds and persists into adulthood is not known. Here, we have established a convenient mouse model and used an 19 F NMR approach to address these questions, test the conditionally essential nutrient hypothesis about Sia supplementation, and assess the prospect of measuring Sia metabolism directly in vivo. Indeed, the neonatal mouse brain uptakes more Sia than the adult brain, and Sia supplementation of neonatal mice improves the cognitive performance of adult mice. The non-invasive 19 F NMR approach and viable mouse model opens unique opportunities for clarifying the interplay of nutritional supplementation, metabolism, and cognitive development.
