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Clinicians say people with spondyloarthritis can continue to have symptoms even when DMARDs have adequately treated inflammation. Patient-reported measures and the lack of a specific, repeatable test make it difficult to tell ongoing inflammatory disease from pain related to structural damage, nociplastic pain or other conditions.
Persistent symptoms do not always mean persistent inflammation in spondyloarthritis (SpA), clinicians told MedPage Today in a report published November 2. The distinction matters because pain after treatment may have several causes, and changing a disease-modifying antirheumatic drug (DMARD) without confirming ongoing inflammatory activity may not address the problem.
Trials of medicines for axial SpA show that many participants do not meet response thresholds, even when a treatment is judged successful. In the source report, phase II-III results for the selective JAK inhibitor filgotinib showed ASAS40 responses in 35% to 40% of recipients, compared with 18% to 21% of placebo recipients. For the anti-IL-17A antibody vunakizumab, 65.6% achieved ASAS20, compared with 42.5% on placebo. These are distinct response measures and trial results; they do not show that every patient’s residual symptoms come from the same cause.
Abhijeet Danve of Yale School of Medicine told MedPage Today that response rates for approved axial SpA DMARDs also leave many patients with symptoms. He said persistent pain can reflect nociplastic pain, degenerative disc disease or facet arthritis, rather than active inflammation alone. Depression and obesity may also contribute, according to Lianne Gensler of the University of California, San Francisco.
Assessment is difficult because SpA care relies heavily on patient-reported symptoms, while clinicians lack a specific physical examination finding or biomarker that reliably establishes inflammatory activity in the spine and sacroiliac joints. Gensler described MRI as the closest available assessment tool, but said it is not specific on its own and is not practical to repeat whenever symptoms occur. The report does not establish that any individual patient’s symptoms are non-inflammatory.
Why Persistent Pain Needs Careful Review
The distinction can shape treatment decisions. If symptoms are assumed to mean uncontrolled inflammation, a clinician may consider switching or cycling through DMARDs. But when pain instead reflects structural damage, nociplastic pain or a comorbidity, changing anti-inflammatory treatment may not resolve it. The source report stresses that this is a clinical challenge, not a reason to dismiss a patient’s symptoms.
Danve told MedPage Today that physical therapy and regular exercise may help some patients with residual symptoms, and mentioned medicines including gabapentin, selective serotonin reuptake inhibitors and muscle relaxants for nociplastic pain. These are options he suggested, not a treatment plan for every person with SpA; treatment decisions depend on a clinician’s assessment of the individual.
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How SpA Response Is Measured
Spondyloarthritis is a group of conditions involving inflammation in the spine or entheses, where tendons and ligaments attach to bone. Axial SpA affects the spine and includes radiographic disease, also called ankylosing spondylitis, and non-radiographic disease. Peripheral SpA can involve symptoms such as heel pain. Initial treatment commonly includes nonsteroidal anti-inflammatory drugs; DMARDs may be used when needed.
The ASAS response measures cited in the report combine patient assessments of overall disease, spinal pain, function and inflammation. ASAS40 requires at least a 40% improvement, with a specified absolute improvement across three of four domains and no worsening in the remaining domain. ASAS20 uses corresponding thresholds of at least 20% improvement. The measures describe response in trials; they are not direct, objective proof that inflammation has or has not disappeared in a particular patient.
The report also notes a 2026 American College of Rheumatology guideline update that favored TNF inhibitors and IL-17 blockers over JAK inhibitors as initial biologic DMARD treatment for ankylosing spondylitis and axial SpA. Separately, an Assessment of SpondyloArthritis International Society consensus definition issued in 2025 describes difficult-to-manage axial SpA as involving failure of at least two biologic or targeted synthetic DMARDs, suboptimal disease control, and problematic symptoms recognized by both patient and rheumatologist.
“It is common to have persistent symptoms despite treatment of inflammation.”
— Abhijeet Danve, MD, MHS, Yale School of Medicine, as quoted by MedPage Today
What Tests Cannot Yet Resolve
The report does not provide a single test or threshold that can reliably determine the cause of residual symptoms for every patient. MRI can help assess inflammation, but Gensler cautioned that imaging findings are not specific on their own and cannot be repeated each time symptoms change. Patient-reported scores also capture experience and function, rather than isolating inflammation as the cause.
It remains unclear from the report how often persistent symptoms after DMARD treatment reflect active inflammatory disease versus damage, nociplastic pain or other factors. It also does not give comparative evidence showing which approach to evaluating residual symptoms leads to better outcomes. Treatment-refractory disease, as described in the report, is narrower than difficult-to-manage disease: it requires objective inflammatory activity and exclusion of non-inflammatory explanations for inadequate response.
Separating Inflammation From Other Causes
For people whose symptoms continue during treatment, the clinical question is whether there is objective evidence of ongoing inflammation and whether other contributors may be present. The report points to the need for assessment rather than automatically changing DMARDs in response to symptoms alone. Danve’s suggestions include physical therapy and regular exercise when residual pain is not driven solely by inflammation.
The source does not announce a new diagnostic test or a change to treatment guidelines. Further research and clinical work will be needed to improve ways of identifying inflammatory activity and to distinguish it from other causes of pain. Until then, the decision to continue, change or supplement treatment remains a matter for patients and their rheumatology teams.
Key Questions
Do persistent symptoms mean a DMARD has failed?
Not necessarily. The report says symptoms can continue even when inflammation has been adequately treated. A clinician needs to assess whether symptoms reflect active inflammation, damage, nociplastic pain or other factors.
What does ASAS40 measure?
ASAS40 is a trial response measure requiring at least a 40% improvement, plus an absolute improvement in at least three of four domains—patient global assessment, spinal pain, function and inflammation—with no worsening in the remaining domain.
Can an MRI show whether SpA inflammation is active?
MRI is described as the closest available assessment tool for axial joint inflammation, but Gensler told MedPage Today that it is not specific on its own. The report says it is also impractical to perform an MRI whenever symptoms occur.
What is difficult-to-manage axial SpA?
The 2025 ASAS consensus definition cited in the report includes failure of at least two biologic or targeted synthetic DMARDs, suboptimal disease control, and problematic signs and symptoms recognized by both the patient and rheumatologist.
What may help when pain is not mainly inflammatory?
Danve suggested physical therapy and regular exercise, and named gabapentin, selective serotonin reuptake inhibitors and muscle relaxants as possible options for nociplastic pain. These are not recommendations for everyone; patients should discuss persistent symptoms and treatment choices with their clinician.
Source: medpagetoday.com
