Background/Purpose: Upadacitinib (UPA), an oral JAK inhibitor, has demonstrated improvements in inflammation and nociceptive pain in late phase clinical trials of patients with axSpA.1,2,3 However, patients may also experience non-nociceptive pain via altered central nervous system modulation (nociplastic), including fibromyalgia (FM), or peripheral nervous system damage (neuropathic). This post hoc analysis of a real-world study in patients with axSpA examined the impact of UPA treatment on non-nociceptive pain and the association of non-nociceptive pain with residual symptoms, sleep disturbance, anxiety, and depression.

Methods: UPSTAND was a 12-month, multicountry, noninterventional, observational study evaluating the effectiveness of UPA on pain in adult patients with axSpA. Safety from UPSTAND has been previously analyzed.4 This analysis used interim data collected after all patients completed at least week (wk) 12. Patients were grouped by severity of neuropathic pain, as captured by painDETECT (< 13, 13-18, and > 18) or severity of nociplastic pain, as captured by widespread pain index (WPI: < 4, 4-6, and > 6). While patients demonstrating active symptoms of FM per clinical diagnosis were excluded from UPSTAND, WPI and symptom severity score (SSS) were used together to assess the presence of nociplastic pain fulfilling FM criteria as per Wolfe et al. 2016: WPI 4-6 and SSS ≥ 9 or WPI ≥ 7 and SSS ≥ 5.5 All other scores (absence of FM) were grouped together. The proportion of patients in each group was reported at baseline (BL) and wk 12. For those with available data, the proportion of patients in each group was reported at wk 24. The association of non-nociceptive pain with measures of disease activity, sleep quality, and symptoms of anxiety/depression was assessed by analyzing the proportion of patients in each group at wk 12 that did or did not achieve ASDAS low disease activity (ASDAS LDA; < 2.1), BASDAI < 4, Pittsburgh Sleep Quality Index Score < 5, and Hospital Anxiety and Depression Scale ≤ 7 at wk 12. The change from BL in total back pain, nocturnal back pain, fatigue (BASDAI question 1), and BASFI at wk 12 was reported for each group.

Results: Overall, UPA treatment was associated with a reduction in the burden of nociplastic and neuropathic pain over time (Figure 1). The proportion of patients in the least severe pain groups increased from BL over time; the proportion of patients in the more severe pain groups or meeting criteria for FM decreased over time. Non-nociceptive pain at wk 12 was associated with residual symptoms, anxiety/depression, and poor sleep (Figure 2). The presence of non-nociceptive pain was associated with smaller improvements in total back pain, nocturnal back pain, fatigue, and BASFI from BL to wk 12 (Figure 3).

Conclusion: In patients with axSpA, treatment with UPA was associated with improvements in non-nociceptive pain. Non-nociceptive pain was associated with residual symptoms, sleep disturbance, signs of anxiety/ depression, and fatigue.1. van der Heijde D, et al. Lancet. 2019;394:2108-17.2. van der Heijde D, et al. Ann Rheum Dis. 2022;81:1515-23.3. Deodhar A, et al. Lancet. 2022;400:369-79.4. Poddubnyy D, et al. [abstract]. Ann Rheum Dis. 2025;83:1.5. Wolfe F, et al. Semin Arthritis Rheum. 2016;46:319-29.

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-treatment-with-upadacitinib-on-non-nociceptive-pain-and-its-relevance-for-the-presence-of-residual-symptoms-in-axial-spondyloarthritis-results-from-a-multicountry-observational-study/