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A MedPage Today report published Nov. 2, 2026, examines why people with spondyloarthritis may continue to have symptoms even when DMARDs have controlled inflammation. Rheumatologists cited pain-processing changes, structural damage and other health conditions, while noting that symptoms alone do not establish treatment-refractory inflammatory disease.
A MedPage Today report published Nov. 2 describes why some people with spondyloarthritis (SpA) continue to have pain and other symptoms after disease-modifying drugs have treated inflammation. Rheumatologists interviewed for the report said symptoms can have several causes, making it difficult to determine whether persistent discomfort signals ongoing inflammatory disease or whether changing medication is likely to help.
The report points to clinical-trial results as evidence that complete symptom relief is not the usual outcome of treatment. In trials of the selective JAK inhibitor filgotinib for axial SpA, 35% to 40% of recipients reached an ASAS40 response, compared with 18% to 21% of placebo recipients. In a trial of the anti-IL-17A antibody vunakizumab, 65.6% of patients reached ASAS20, compared with 42.5% of those receiving placebo. These measures reflect improvement across patient-reported domains, not proof that every symptom has resolved.
Abhijeet Danve of Yale School of Medicine told MedPage Today that ASAS40 responses in successful trials of approved axial SpA treatments are generally achieved by about 40% to 55% of patients. He said those results indicate that residual symptoms can persist even when inflammation has been adequately treated. The report also describes possible contributors including nociplastic pain, degenerative disc disease, facet arthritis, structural damage, depression and obesity.
Clinicians face limits in monitoring disease activity. The report says SpA lacks a reliable objective measure that can readily distinguish inflammatory pain from other sources. Lianne Gensler of the University of California, San Francisco, said there is no physical examination that clearly identifies inflammation in the spine’s axial joints. MRI can help, she said, but it is not specific on its own and is not practical for every episode of symptoms.
When Symptoms Do Not Mean Inflammation
The distinction matters because persistent symptoms do not automatically show that a DMARD has failed. If clinicians interpret pain alone as active inflammation, they may change or cycle treatments without addressing the source of symptoms. The report also notes that some patients have treatment-refractory inflammatory disease, which requires evaluation rather than assuming symptoms are non-inflammatory.
The report describes physical therapy and regular exercise as options Danve suggested for residual symptoms, alongside medications such as gabapentin, selective serotonin reuptake inhibitors and muscle relaxants when nociplastic pain is involved. These approaches do not replace assessment for active disease; treatment depends on the cause of a patient’s symptoms.
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How SpA Response Is Defined
Spondyloarthritis is a group of conditions involving inflammation in the spine and/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 cause symptoms such as heel pain. Treatment may begin with nonsteroidal anti-inflammatory drugs, with DMARDs used in appropriate cases.
The report says a 2026 American College of Rheumatology guideline update favored TNF inhibitors and IL-17 blockers over JAK inhibitors as initial biologic DMARD treatment for ankylosing spondylitis and axial SpA. It also notes that ASAS response measures combine patient assessments of disease, spinal pain, function and inflammation. ASAS40 requires at least a 40% improvement, with specified absolute improvement across at least three of four domains and no worsening in the remaining domain; ASAS20 uses a lower improvement threshold.
In 2025, the Assessment of SpondyloArthritis International Society issued a consensus definition of difficult-to-manage axial SpA: failure of at least two biologic or targeted synthetic DMARDs, suboptimal disease control, and problematic signs and symptoms as perceived by both the patient and rheumatologist. The report distinguishes treatment-refractory disease as a subset requiring objective evidence of inflammatory activity and exclusion of non-inflammatory reasons for poor response.
“It is common to have persistent symptoms despite treatment of inflammation.”
— Abhijeet Danve, MD, MHS, Yale School of Medicine, speaking to MedPage Today
Separating Active Disease From Pain
There is no single monitoring test described in the report that can reliably identify the cause of every persistent symptom. MRI findings are not fully specific, and patient-reported measures can reflect pain and function without independently establishing active inflammation. The report does not provide a universal method for deciding when to change treatment; that remains a clinical assessment based on symptoms, examination, imaging and other evidence.
It also remains unclear how often residual symptoms in the wider SpA population are primarily inflammatory, pain-related, structural or linked to comorbidities. The cited trial response rates apply to particular studies and measures and should not be treated as an estimate of every patient’s likely outcome. The source material gives no further details on the phase II-III trial designs or longer-term results for filgotinib and vunakizumab.
Evaluation Beyond Drug Response
Patients with continuing symptoms can discuss them with their rheumatologist rather than conclude from pain alone that treatment has failed. Clinicians may assess for objective inflammatory activity while considering damage, nociplastic pain and other conditions. Danve’s suggested supportive options include exercise and physical therapy, with medication choices tailored to the suspected pain mechanism and the individual patient.
Researchers and clinicians continue to refine definitions of difficult-to-manage and treatment-refractory axial SpA. Further evidence may clarify how to identify inflammatory activity and which approaches help patients whose symptoms persist despite inflammation control. The report does not announce a new diagnostic test or a change to treatment guidance.
Key Questions
Do symptoms after DMARD treatment mean the medication has failed?
Not necessarily. The report says symptoms may persist because of nociplastic pain, structural damage, degenerative changes or comorbidities, as well as active inflammation. A clinician’s assessment is needed to distinguish among them.
What does ASAS40 measure?
ASAS40 is a response measure requiring at least a 40% improvement and a specified absolute improvement in at least three of four domains: patient global assessment, spinal pain, function and inflammation, without worsening in the remaining domain.
Can an MRI confirm that persistent pain is inflammatory?
The report describes MRI as one of the closest available ways to assess axial-joint inflammation, but Gensler said it is not specific on its own. It is also not practical to repeat an MRI whenever symptoms occur.
What is difficult-to-manage axial SpA?
Under the 2025 ASAS consensus definition cited in the report, it involves failure of at least two biologic or targeted synthetic DMARDs, suboptimal disease control, and problematic symptoms recognized by both the patient and rheumatologist. Treatment-refractory disease is a subset requiring objective inflammatory activity and exclusion of non-inflammatory causes.
Source: medpagetoday.com
