← 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.
31 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.
Risk of Cancer According to Duration of Targeted Therapy Exposure in Spondyloarthritis: A Nationwide Cohort Study From the French Health Insurance Database
Arthritis & Rheumatology
Following 56,591 people with spondyloarthritis in France for a median of five years, those taking a targeted therapy for more than six months a year had slightly lower overall cancer risk than those taking it less. Staying on a TNF, IL-17 or JAK drug did not raise cancer risk in this very large real-world group, which addresses a common worry about long-term treatment.
Dynamics of interleukin-23/interleukin-17 axis and type 1 regulatory T cells across disease stages in axial spondyloarthritis.
Clinical and experimental rheumatology
Comparing early, non-radiographic axial spondyloarthritis with established radiographic disease, people with early disease had more IL-23 in their blood and more IL-23-producing dendritic cells, while IL-17 levels were the same, and a calming cell type called Tr1 was lower early on. IL-23 may matter most at the start of the disease, which fits why IL-23 blockers disappointed in trials that mostly enrolled established disease.
Impact of bimekizumab on CANDEN spinal MRI inflammation & structural lesions in radiographic axial spondyloarthritis: 2-year phase 3 results.
Rheumatology (Oxford, England)
In 102 people with radiographic axial spondyloarthritis scanned repeatedly over two years on bimekizumab (Bimzelx), spinal inflammation on MRI fell sharply by 16 weeks and stayed down, fat lesions rose a little early then stopped changing, and erosion and new bone barely moved. The inflammation the drug is aimed at clears quickly and the structural damage that worries people most showed minimal change over two years.
Impact of Dual Interleukin-17A and Interleukin-17F Inhibition with Bimekizumab on Inflammatory and Structural Lesions in Axial Spondyloarthritis: MRI and Radiographic Outcomes from the Phase 3 BE MOBILE 1 and 2 Studies and their Open-Label Extension.
Arthritis & rheumatology (Hoboken, N.J.)
Across both bimekizumab (Bimzelx) phase 3 trials, MRI inflammation in the sacroiliac joints and spine dropped substantially within a year, erosion scores fell gradually, and X-rays at two years showed almost no progression in either the joints or the spine. For a drug this new, that is early evidence it may slow structural damage, not just symptoms, though two years is short for a disease measured in decades.
Real-world drug survival and treatment outcome of ixekizumab in patients with spondyloarthropathies.
Frontiers in immunology
In a real-world cohort on ixekizumab (Taltz), about 60 percent of people with ankylosing spondylitis were still on the drug at one year and the median time on treatment was just under two years, with lack of effect the main reason for stopping and side effects uncommon. Starting it earlier in the treatment sequence, rather than third-line or later, more than halved the chance of stopping.
Residual activated Th17 cells during low disease activity are associated with disease worsening in radiographic axial spondyloarthritis: A pilot study.
Joint bone spine
In 21 people with radiographic axial spondyloarthritis whose disease looked quiet, those with more activated Th17 cells still circulating were far more likely to lose control over the next six months; nearly half flared, versus none in the low-Th17 group. Feeling well and having a low score may not mean the inflammatory engine has switched off, and a blood test might one day tell the difference.
Reduction of CXCR3+CCR6+ CD4+ T Cells and IL-17+ RORγt+ CD4+ T Cells During Secukinumab Treatment Identifies Patients With Axial Spondyloarthritis Responsive to Subsequent Biologic Therapy.
ACR open rheumatology
Among people who did not respond to secukinumab (Cosentyx), those whose IL-17-producing T cells had fallen during treatment went on to respond to either a higher dose or a switch to a TNF blocker, while those whose cells had not changed failed all three options. A blood test during the first biologic might one day predict whether switching is worth it.
Korean College of Rheumatology treatment recommendations for patients with axial spondyloarthritis: 2026 update.
Journal of rheumatic diseases
Korea's 2026 rheumatology guideline sets out 20 recommendations for axial spondyloarthritis: treat to a target, measure disease with ASDAS, stop smoking and exercise, start with anti-inflammatories, and move to a TNF, IL-17 or JAK drug when those fail, with guidance on switching, tapering and safety checks. It is a clear, current picture of what standard care looks like in 2026.
Therapeutics in Axial Spondyloarthritis: A Review of What Works - SPARTAN 2026 Annual Meeting Proceedings.
Current rheumatology reports
A 2026 expert review concludes that TNF, IL-17 and JAK drugs all control symptoms in axial spondyloarthritis, that evidence for slowing spinal damage is strongest for TNF blockers and not yet established for JAK inhibitors, and that structured exercise, in sessions of an hour or less, measurably improves activity, function, pain and fatigue. Obesity predicts worse disease and a weaker response to TNF drugs.
Why Do Some Therapies Work While Others Fail? Mechanisms of Response and Emerging Treatments in axial Spondyloarthritis: 2026 SPARTAN Annual Meeting Proceedings.
Current rheumatology reports
This 2026 review explains why some drugs work in axial spondyloarthritis and others do not: HLA-B27 can present fragments that expand a specific population of T cells making TNF and IL-17, while IL-23 matters less once inflammation is established, which fits the failure of IL-23 blockers. It names the next targets, including an interferon signature seen in people who fail TNF and IL-17 drugs and a macrophage factor called MIF.
An Increased Circular RNA, circRNPS1, in T Cells of Ankylosing Spondylitis Patients Enhances the MEK/ERK Signaling and Inflammation Mediated by T Cell Activation via Stabilization of hnRNPK and VAV1.
International journal of molecular sciences
T cells from people with ankylosing spondylitis carry raised levels of a circular RNA called circRNPS1, which stabilises two proteins that push the cells to make IL-17 and other inflammatory signals; blocking it in the lab calmed those cells down. It is one explanation for why HLA-B27 alone does not cause AS, and a possible new drug target that works inside the T cell rather than on the cytokines it releases.
Experimental models of spondyloarthritis: Pathophysiological insights and translational challenges.
Journal of autoimmunity
This review takes stock of the mouse and rat models used to study spondyloarthritis and what each has taught us: the gut-joint connection, IL-23-driven inflammation where tendons meet bone, and the TNF pathways that became today's drugs. No single model captures the whole disease, which is one reason lab findings so often fail to translate, and the authors map what better models would need.
Bimekizumab efficacy in male and female patients with axial spondyloarthritis: 52-week results from the phase 3 BE MOBILE trials.
Rheumatology (Oxford, England)
Across two large trials, men with axial spondyloarthritis responded faster to bimekizumab (Bimzelx) than women at 16 weeks, but by one year women had caught up on most measures, and MRI and blood inflammation fell by similar amounts in both sexes. The drug works for both; women may just need longer before judging whether it is helping.
Bimekizumab Long-Term Safety and Efficacy Across the Spectrum of Axial Spondyloarthritis Over 3 Years: Results From 2 Phase III Studies.
The Journal of rheumatology
Three years of bimekizumab (Bimzelx) in 574 people across the whole axial spondyloarthritis spectrum showed no deaths or major heart events, with mild thrush-type fungal infections the main side effect and rates falling by year three. Benefits held steady, so for people weighing a long-term IL-17 drug the safety picture so far is reassuring.
From IL-23/IL-17 to GM-CSF: how is the immuno-inflammatory continuum reshaped in spondyloarthritis?
Frontiers in immunology
This review argues that the simple chain of IL-23 driving IL-17 only describes early disease: later, IL-17 is produced by several cell types independently of IL-23, and a second signal, GM-CSF, locks macrophages into a lasting inflammatory state. That would explain why IL-23 blockers failed in axial spondyloarthritis, why IL-17 blockers work, and why controlling inflammation does not always stop new bone forming.
Mechanistic study of IL-17 inhibitors in alleviating inflammation in ankylosing spondylitis by regulating Treg cell function through modulation of the Ahr signaling pathway.
Human cell
In a mouse model of ankylosing spondylitis, secukinumab (Cosentyx) reduced inflammation partly by switching on a receptor called Ahr, which boosted the calming regulatory T cells; blocking Ahr cancelled the benefit. IL-17 drugs may work not only by removing an inflammatory signal but by actively restoring the immune system's brakes.
Refinement of the Pathogenic T Cell Receptor Motif Suggests Type 17 CD8+ T Cells Initiate HLA-B*27-associated Autoimmunity.
bioRxiv : the preprint server for biology
A specific family of killer T cells that recognise HLA-B27 was found in people with axial spondyloarthritis, uveitis and psoriatic arthritis but not healthy controls, and these cells appear to switch into an IL-17-producing mode in the gut. It is a direct line from the HLA-B27 gene, through the gut, to the inflammation that IL-17 drugs block, in one set of cells.
Association of dietary sodium intake with IL-17-mediated diseases in the UK biobank.
Clinical nutrition ESPEN
In the UK Biobank, higher estimated salt intake went with slightly higher odds of IL-17-driven conditions such as psoriasis, psoriatic arthritis and rheumatoid arthritis, but there was no link at all with ankylosing spondylitis. Despite plausible lab reasons to expect one, this large study does not support cutting salt as a way to influence AS.
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.