← Map/THREAD · IL23-IL17-AXIS
IL-23 / IL-17 Axis
The cytokine pathway most newer AS biologics target, secukinumab, ixekizumab, bimekizumab.
Why this is a thread
This is the inflammatory pathway most newer AS biologics target. The drugs you may have heard of, secukinumab (Cosentyx), ixekizumab (Taltz), bimekizumab (Bimzelx), all block IL-17. The reason these drugs work for many people is that IL-23 drives a type of T cell (called Th17) to produce IL-17, and IL-17 drives much of the inflammation in AS. Papers in this thread cover how the pathway works, who responds well to which drug, and why some people don't respond at all.
13 papers on the board
Current status and emerging trends in biological therapies for ankylosing spondylitis: a bibliometric analysis (2004–2024)
Medicine (LWW)
Bibliometric analysis of biological therapies for AS over 2004-2024. Confirms three pillars, TNF, IL-17, and JAK inhibitors, and a persistent inadequate response in a meaningful subset of patients across all three classes.
Recent advances in biologic therapies for ankylosing spondylitis: a 2024 update
Allergologia et Immunopathologia
Comprehensive bDMARD review covering TNF, IL-17, and JAK inhibitor classes with their efficacy and safety profiles across the AS treatment landscape. Confirms a meaningful patient subset still has inadequate response across all three drug classes.
Gut microbiota and ankylosing spondylitis: current insights and future challenges
Microbial Cell
Comprehensive review of how gut bacterial imbalance disrupts the IL-23/IL-17 inflammatory pathway and weakens the intestinal barrier in AS. Identifies the lack of standardised methodology and large cohorts as the bottleneck for translating this into treatments.
Dysbiosis of Gut Microbiota in Ankylosing Spondylitis Patients
Dove Medical Press
Confirms that intestinal dysfunction precedes or amplifies systemic inflammation in AS. Frames gut microbiota as the convergence point where genetic, immune, and microbial factors meet.
Advances in Axial Spondyloarthritis Treatment: The Role of Janus Kinase Inhibitors
International Journal of Rheumatic Diseases
Reviews the JAK inhibitor class, tofacitinib, upadacitinib, filgotinib, for axial spondyloarthritis. The 2025 CRA/SPARCC guidelines still place TNF inhibitors first-line, with JAK inhibitors recommended when TNFi is contraindicated or for patients with comorbid IBD.
Breaking boundaries in ankylosing spondylitis: how innovative cell therapies reshape immunity
Frontiers in Immunology
Reviews mesenchymal stem cell and CAR-T cell therapy approaches for AS. MSC therapy shifts inflammatory M1 macrophages toward anti-inflammatory M2; CAR-T is still experimental for AS specifically. Current treatments fail to improve long-term prognosis, cell therapy is positioned as the next frontier.
The Role of IL-23 in the Development of Inflammatory Diseases
Biology (MDPI)
Maps the IL-23/Th17/IL-17 axis across psoriasis, rheumatoid arthritis, IBD, and multiple sclerosis. Confirms IL-23 as a key cross-disease therapeutic target, and reviews the current and emerging biologics that aim at it.
Efficacy of JAK inhibitors in immune-mediated inflammatory diseases: 2024 update of an international consensus statement
Annals of the Rheumatic Diseases
Systematic literature review of JAK inhibitor efficacy across immune-mediated inflammatory diseases. Effective broadly, but isoform selectivity (JAK1/2/3/TYK2) and the data on tapering or withdrawal remain unclear.
The role of gut microbiota in autoimmune disease progression and therapy: a comprehensive synthesis
Frontiers in Microbiomes
Review and meta-analysis of dysbiosis across rheumatoid arthritis, multiple sclerosis, and type 1 diabetes. Identifies bidirectional gut-immune interactions via mucosal modulation and T-regulatory cell activity.
Gut microbiome and immune system crosstalk in chronic inflammatory diseases
Microorganisms
Review covering rheumatoid arthritis, IBD, psoriasis, lupus, asthma, and vasculitis, all sharing gut-immune disruption as a common mechanism. Synthesises FMT, dietary modification, and probiotic/prebiotic approaches.
Quantitative Alterations in Short-Chain Fatty Acids in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
Biomolecules
Systematic review and meta-analysis of short-chain fatty acids (SCFA), particularly butyrate, across IBD subgroups. Butyrate is significantly reduced in patients vs controls and suppresses pro-inflammatory cytokines, but clinical trials remain inconsistent due to delivery, degradation, and unstandardised dosing.
A disease-associated gene desert directs macrophage inflammation through ETS2
Nature
Identified a single 'switch' gene called ETS2, sitting on chromosome 21, that turns immune cells inflammatory across AS, IBD, and several other related diseases. Because no current drug targets ETS2, this points to a treatment direction beyond what's already available with TNF and IL-17 blockers.
A randomized, double-blinded, phase 2 trial of EDP1815, an oral immunomodulatory preparation of Prevotella histicola, in adults with mild-to-moderate plaque psoriasis
Frontiers in Medicine
Phase 2 trial of EDP1815, a non-live oral biotherapeutic derived from Prevotella histicola, for mild-to-moderate plaque psoriasis. Hits the same Th1/Th2/Th17 pathway central to AS. Clinical efficacy confirmed in psoriasis but discontinued in atopic dermatitis: same pathway, different microenvironment, different outcome.