The treatment landscape in axial spondyloarthritis—do we need new therapies?

Despite major therapeutic advances, many patients with axial spondyloarthritis (axSpA) fail to achieve remission or even low disease activity with currently available advanced therapies. This highlights an urgent need to understand why treatment responses remain suboptimal and how management can be improved. Several mechanisms contribute to persistent symptoms. Misdiagnosis and overdiagnosis remain frequent, often due to nonspecific imaging findings being misattributed to axSpA. Among correctly diagnosed patients, a substantial proportion experience pain not directly driven by inflammation. Nociplastic pain—frequently associated with fatigue, anxiety, depression, and sleep disturbances—is the predominant mechanism, while neuropathic pain is less common. These patients do not benefit from escalation of anti-inflammatory therapy but instead require tailored approaches addressing nociplastic pain, including structured exercise, cognitive-behavioural therapy, and pharmacological agents. However, robust clinical trial data in axSpA populations are lacking, and studies evaluating these interventions as add-on strategies are urgently needed. A smaller but clinically important subset of patients demonstrates true treatment-refractory (TR) axSpA, with objective inflammation persisting despite multiple biologic or targeted synthetic disease-modifying antirheumatic drugs. Novel therapeutic approaches under investigation include dual-targeted therapy with complementary mechanisms, selective depletion of pathogenic T cells, modulation of the HLA-B27 immunopeptidome through endoplasmic reticulum aminopeptidase 1/2 inhibition, and blockade of macrophage migration inhibitory factor. The primary challenge in axSpA today—besides the problem of the correct diagnosis—is to optimise the use of existing therapies for pain not related to inflammation, while simultaneously developing innovative options for TR disease. Together, these efforts will determine whether remission can become an attainable goal for all patients.