← Map/THREAD · TNF-INHIBITION
TNF-α Inhibition
The first major shift in AS treatment. Still first-line in most guidelines.
Why this is a thread
TNF blockers were the first major shift in AS treatment. They include adalimumab (Humira), etanercept (Enbrel), infliximab (Remicade), golimumab (Simponi), and certolizumab (Cimzia). Most guidelines still place them as first-line treatment for AS, they remain the most-prescribed biologic class. Papers in this thread cover their mechanism, comparative effectiveness, immunogenicity (when patients build up antibodies that reduce the drug's effect), and how they sit alongside the newer drug classes that came after them.
16 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.
Disease-modifying anti-rheumatic drugs and systemic glucocorticoid use and risk of vertebral fractures in axial spondyloarthropathies: a systematic review and meta-analysis.
Clinical rheumatology
Across ten studies, biologic and conventional disease-modifying drugs neither raised nor lowered the risk of spinal fractures in axial spondyloarthritis, and TNF and IL-17 drugs were no different from each other, but steroid tablets raised fracture risk by about 38 percent. Controlling inflammation does not by itself protect the spine from breaking, so bone health needs its own attention, and steroids are best kept to a minimum.
Male sexual dysfunction associated with TNF-α inhibitors: an indication-stratified global pharmacovigilance analysis.
Frontiers in pharmacology
Searching the WHO global side-effect database, researchers found no overall link between TNF blockers and male sexual dysfunction, but among reports from people with ankylosing spondylitis there was a modest excess for adalimumab and etanercept that did not hold up at the level of specific symptoms. The authors call it hypothesis-generating, which is fair: worth knowing about, not a reason to change treatment.
Comparison of the Risk of Acute Anterior Uveitis Flare Between Adalimumab and Subcutaneous Infliximab in Patients with Radiographic Axial Spondyloarthritis and Prior Acute Anterior Uveitis: A Randomized Controlled Trial.
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
In a head-to-head trial of 56 people with radiographic axial spondyloarthritis and recent eye inflammation, adalimumab (Humira) and under-the-skin infliximab (Remicade) each saw one uveitis flare over 48 weeks. For someone choosing a TNF blocker partly to protect their eyes, both options look equally good on this evidence.
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.
Ten-Year Public Expenditure Savings Associated with TNF Inhibitor Biosimilars under Australia's Pharmaceutical Benefits Scheme.
Clinical pharmacology and therapeutics
Biosimilar versions of TNF blockers saved Australia's Pharmaceutical Benefits Scheme about 562 million dollars over ten years, with etanercept biosimilars delivering most of it and adalimumab less because its biosimilars arrived late; ankylosing spondylitis was the second-largest source of savings after rheumatoid arthritis. For Australians on a TNF blocker, this is the system-level reason a biosimilar switch may be suggested.
Longitudinal monitoring of adalimumab levels and anti-adalimumab antibodies in Chinese patients with ankylosing spondylitis: a prospective cohort study
Frontiers in Immunology
Tracking 140 Chinese patients on adalimumab (Humira) alone for ankylosing spondylitis, 90 percent developed antibodies against the drug within months, and those with high antibody levels had far lower drug concentrations and roughly half the response rate of those with low levels. Measuring drug and antibody levels in the blood could show early who is heading for treatment failure, and the study sets target concentrations for that.
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.
Paradoxical psoriasis in axial spondyloarthritis and rheumatoid arthritis treated with b/tsDMARDs: a retrospective cohort study.
Clinical rheumatology
Among 1,588 people on biologics for axial spondyloarthritis or rheumatoid arthritis, about 2 percent developed a psoriasis-like rash caused by the drug, almost always a TNF blocker, with smoking the only independent risk factor; stopping the drug cleared it in most, and switching to a non-TNF drug worked. If a new rash appears on a TNF blocker, it may be the drug, and there are good alternatives.
Association between type 2 diabetes and short-term clinical response to TNF inhibitors in patients with ankylosing spondylitis: a propensity score-matched retrospective cohort study.
Clinical rheumatology
In a single-centre study of people with ankylosing spondylitis starting a TNF blocker, those with type 2 diabetes were far less likely to respond in the short term, 20 percent versus 75 percent in the matched comparison. The authors are careful to call it a signal rather than a proof, since blood sugar control and weight were not fully accounted for, but if you have both conditions it is a conversation worth having before judging a drug a failure.
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.
The role of ETS2 in macrophage inflammation
DNA and Cell Biology
Direct follow-up to the 2024 Nature paper. Shows that ETS2 turns on several inflammatory signals at once, TNF, IL-23, IL-1β, and TL1A, the same signals current biologic drugs target one at a time.
Gut microbiota in rheumatoid arthritis: mechanistic insights, clinical biomarkers, and translational perspectives
Autoimmunity Reviews
Review of the gut microbiota in rheumatoid arthritis, with diet as an upstream variable: Western diet → dysbiosis → inflammation; Mediterranean and plant-based diets → microbial diversity → immune tolerance. Same dysbiosis mechanism as the AS papers, with an environmental modifier layer the AS papers don't yet emphasise.