The seronegative spondyloarthropathies — ankylosing spondylitis, non-radiographic axial spondyloarthritis (nr-axSpA), psoriatic arthritis, and related conditions — are driven largely by the IL-23/Th17 axis, which sets them apart from other arthritides. Recent advances have redefined treatment for patients who respond incompletely to TNF inhibitors.
JAK inhibitors
Upadacitinib significantly improved ASAS40 response in ankylosing spondylitis and nr-axSpA refractory to biologics (in the SELECT-AXIS 2 program) and is approved across axial spondyloarthritis and psoriatic arthritis, offering an oral option for patients intolerant of or refractory to biologics. Class-wide monitoring for infection (including herpes zoster), thromboembolism, and cardiovascular risk applies.
IL-17 inhibition, now including dual IL-17A/F blockade
Ixekizumab and secukinumab (IL-17A inhibitors) are effective across axial and peripheral disease, including in TNF-inadequate responders. The key update is bimekizumab, which blocks both IL-17A and IL-17F: on the strength of the BE MOBILE 1 and 2 (axial) and BE OPTIMAL and BE COMPLETE (psoriatic) trials, it was FDA-approved in 2024 for psoriatic arthritis, nr-axSpA, and ankylosing spondylitis — the first IL-17A/F inhibitor across the spondyloarthritis spectrum. Oral candidiasis is more common with dual IL-17 blockade, and IL-17 inhibitors as a class warrant caution given the risk of new or worsening inflammatory bowel disease and uveitis.
Foundation and future directions
TNF inhibitors remain standard after NSAIDs for most axial disease and moderate-to-severe psoriatic arthritis, but up to 40% of patients do not achieve full remission — the gap these newer classes address. Conventional DMARDs still have a role in peripheral (especially psoriatic) arthritis but not isolated axial disease. GM-CSF inhibition, microbiome-based strategies, and biomarker/imaging-guided precision approaches are under active investigation, and updated axial spondyloarthritis treatment guidelines continue to refine sequencing.
| Agent/class | Indications | Efficacy | Notable risks |
|---|---|---|---|
| Upadacitinib | AS, nr-axSpA, PsA | ASAS40 improvement vs placebo | Herpes zoster, infection, VTE |
| Ixekizumab / secukinumab | axSpA, PsA | Effective incl. TNF-IR | IBD, uveitis, candidiasis |
| Bimekizumab | AS, nr-axSpA, PsA | Approved 2024 (dual IL-17A/F) | Oral candidiasis, fungal infection |
| TNF inhibitors | axSpA, PsA | Standard first-line biologic | Infection, TB reactivation |
Further reading: SELECT-AXIS 2 upadacitinib (Deodhar et al., Lancet 2022); BE MOBILE 1/2 bimekizumab (van der Heijde et al., 2023) and 2024 approval; COAST-X ixekizumab; axial spondyloarthritis treatment guidelines (2023–2026).