Early observations and pilot data that first suggested a new direction
Axial spondyloarthritis (axSpA) treatment was limited to NSAIDs and physical therapy until anti-TNF agents demonstrated efficacy. The ATLAS trial was the pivotal RCT establishing adalimumab for ankylosing spondylitis. Among 315 patients, adalimumab achieved ASAS20 response in 58.2% versus 20.6% placebo at week 12 (p<0.001) and partial remission in 22.1% versus 5.6% (p<0.001). This transformed the treatment landscape for patients with active AS despite NSAID therapy.
Landmark RCTs and pivotal trials that established the evidence base
The ABILITY-1 trial extended biologic therapy to non-radiographic axial spondyloarthritis (nr-axSpA), a condition not previously treated with biologics. Among 185 patients with nr-axSpA, adalimumab achieved ASAS40 in 36% versus 15% placebo at week 12 (p<0.001). The MEASURE 1 and 2 trials established secukinumab (anti-IL-17A) as a second biologic mechanism for AS. In MEASURE 2 (219 patients), secukinumab 150 mg achieved ASAS20 of 61% versus 28% placebo at week 16 (p<0.001), providing an alternative for anti-TNF failures.
Follow-up studies, subgroup analyses, and real-world validation
The SELECT-AXIS 1 trial introduced the first JAK inhibitor for axSpA. Among 187 patients with active AS, upadacitinib 15 mg achieved ASAS40 in 52% versus 26% placebo at week 14 (p=0.0003). This oral therapy provided a novel mechanism of action for patients with inadequate response to NSAIDs, offering convenience and a different safety/efficacy profile. The trial established JAK inhibitors as a third therapeutic class for axSpA alongside anti-TNF and anti-IL-17 agents.
Integration into clinical practice guidelines and recommendations
ACR/SAA/SPARTAN 2019 and ASAS/EULAR 2022 guidelines recommend NSAIDs as first-line, with biologic DMARDs (anti-TNF or anti-IL-17) for patients with active disease despite adequate NSAID trial. JAK inhibitors (upadacitinib, tofacitinib) are included as options, with similar caveats as in RA regarding cardiovascular and malignancy risk in at-risk populations. The unified axSpA concept (encompassing both nr-axSpA and AS) is now embedded in treatment guidelines.
ASAS/EULAR
NSAIDs first-line; biologic DMARDs (anti-TNF or anti-IL-17) for active disease despite NSAIDs; JAK inhibitors as alternative option
ACR/SAA/SPARTAN
NSAIDs first-line; anti-TNF strongly recommended over other biologics for NSAID-refractory axSpA; secukinumab for anti-TNF failures
Now
Current standard of care and ongoing research directions
Axial spondyloarthritis treatment now encompasses three biologic/targeted DMARD classes: anti-TNF, anti-IL-17, and JAK inhibitors, all available for both radiographic and non-radiographic disease. The treatment paradigm follows a step-up approach from NSAIDs to advanced therapies. Head-to-head comparisons between mechanisms are limited, and treatment selection is guided primarily by comorbidities, extra-articular manifestations, and safety considerations. Emerging areas include whether early biologic therapy can prevent radiographic progression and the potential role of dual-targeted therapies.
What biologic options exist for ankylosing spondylitis?+
Three mechanism classes are available: anti-TNF agents (adalimumab, etanercept, infliximab, golimumab, certolizumab — ATLAS showed ASAS20 58.2% vs 20.6% placebo), anti-IL-17A agents (secukinumab, ixekizumab — MEASURE showed ASAS20 61% vs 28% placebo), and JAK inhibitors (upadacitinib, tofacitinib — SELECT-AXIS showed ASAS40 52% vs 26% placebo). All require prior NSAID failure.
Can non-radiographic axial spondyloarthritis be treated with biologics?+
The ABILITY-1 trial established adalimumab efficacy in nr-axSpA (ASAS40 36% vs 15% placebo, p<0.001). Subsequent trials confirmed secukinumab and upadacitinib efficacy in nr-axSpA. The unified axSpA concept means that biologics and targeted therapies are available for both radiographic (AS) and non-radiographic forms when disease remains active despite NSAIDs.
