Upadacitinib May Reduce Non-Nociceptive Pain in axSpA

Treatment with upadacitinib is associated with improvements in non-nociceptive pain among patients with axial spondyloarthritis (axSpA), with reductions found for both neuropathic and nociplastic pain scores, according to study results presented at the American College of Rheumatology (ACR) Convergence 2025, held from October 24 to 29, in Chicago, IL.

The oral Janus kinase inhibitor upadacitinib has previously shown benefit for reducing inflammation and nociceptive pain in axSpA. However, patients may also experience non-nociceptive pain — including nociplastic and neuropathic pain — which can contribute to ongoing symptoms such as sleep disturbances, anxiety, and depression. Thus, researchers conducted a post hoc analysis of a 12-month, multi-country, noninterventional, observational study to assess how upadacitinib affects non-nociceptive pain scores.

Interim data from the UPSTAND study were used for analysis, after patients completed at least week 12. Non-nociceptive pain was measured with the painDETECT questionnaire for neuropathic pain; the widespread pain index (WPI) and symptom severity score (SSS) were used to quantify nociplastic pain.

The percentages of patients in each pain severity group were reported at baseline, week 12, and week 24 when available. Associations were analyzed between pain severity and disease activity, sleep quality, anxiety, and depression.

Non-nociceptive pain was associated with residual symptoms, sleep disturbance, signs of anxiety/depression, and fatigue.

At baseline, 48.9% of patients had a high likelihood of nociplastic pain (WPI > 6), which decreased to 27.3% at week 12 and 24.1% at week 24. Similarly, the number of patients meeting fibromyalgia criteria (WPI + SSS) decreased from 48.7% at baseline to 27.2% at week 12 and 22.8% at week 24. The percentage of patients with a high likelihood of neuropathic pain (painDETECT > 18) fell from 26.2% at baseline to 11.9% at week 12.

Upadacitinib treatment was associated with a reduction in both neuropathic and nociplastic pain over time. By week 12, the percentage of patients in less severe pain groups increased, while percentages of those in more severe pain groups and the number of patients who met fibromyalgia criteria decreased.

Non-nociceptive pain at week 12 was correlated with residual symptoms including anxiety, depression, and poor sleep quality. Patients with a low likelihood of nociplastic or neuropathic pain at week 12 were more likely to achieve disease control — including low disease activity — better sleep quality, and normal scores for anxiety and depression compared against those with persistent non-nociceptive pain.

In addition, greater improvements from baseline to week 12 were observed in total and nocturnal back pain, fatigue, and function among patients with a low likelihood of non-nociceptive pain, whereas smaller improvements were seen among those with higher nociplastic or neuropathic pain scores.

“Non-nociceptive pain was associated with residual symptoms, sleep disturbance, signs of anxiety/depression, and fatigue,” the study authors concluded.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Rheumatology Advisor