The Janus kinase (JAK) inhibitor upadacitinib provides early and durable reductions in axial spondyloarthritis (axSpA) pain, with links to long-term disease control outcomes, according to a recent post hoc analysis of key phase 2/3 trials.

Pain remains a dominant and debilitating feature of axSpA, and effective control is a persistent unmet clinical need.

A post hoc analysis of the SELECT-AXIS 1 and SELECT-AXIS 2 programmes aimed to assess the efficacy of the JAK inhibitor upadacitinib 15 mg once daily across several pain measures over two years, and to explore whether early pain improvement predicts longer-term disease control. The results were published in the journal Rheumatology and Therapy.

Data were drawn from three randomised, double-blind, placebo-controlled trials that included patients with non-radiographic axSpA (nr-axSpA) or radiographic axSpA (r-axSpA) who were naive to biologic disease-modifying antirheumatic drugs (bDMARDs-naive), had an inadequate response to them (bDMARD-IR).

In the SELECT-AXIS 1 bDMARD-naive r-axSpA study, 93 patients received upadacitinib, compared with 94 who received placebo. Similarly, in the SELECT-AXIS 2 bDMARD-IR r-axSpA study, 211 and 209 patients were randomised to upadacitinib and placebo, respectively.

In the nr-axSpA SELECT-AXIS 2 study, which included both bDMARD-naive and bDMARD-IR patients, 156 received upadacitinib and 157 received placebo.

Mean pain scores were high, at approximately 6.8–7.5 in the patient’s global assessment of pain 0–10 numeric scale, indicating a significant disease burden.

Primary endpoints included the mean change from baseline in the patient’s global assessment of pain. Additionally, the proportions achieving ≥30%, ≥50% and ≥70% reductions from baseline, or a minimal clinically important difference (MCID), defined as a ≥1-point or ≥15% reduction in global pain, were evaluated.

Secondary outcomes included total back pain and associations with long-term disease activity measures such as Assessment of SpondyloArthritis International Society (ASAS) partial remission and Ankylosing Spondylitis Disease Activity Score (ASDAS).

Upadacitinib and axSpA pain outcomes

Upadacitinib was associated with significantly greater reductions in pain compared with placebo across all patient groups. Improvements were observed as early as week one in bDMARD-IR and nr-axSpA populations and by week two in bDMARD-naive patients (all P<0.001 for most comparisons).

Higher proportions of patients achieved ≥30%, ≥50% and ≥70% reductions in pain and reached MCID with upadacitinib. These improvements were generally maintained or further enhanced through 104 weeks in patients receiving continuous therapy.

Patients who switched from placebo to upadacitinib at week 14 (r-axSpA) or week 52 (nr-axSpA) demonstrated comparable pain reductions over time.

Similar trends were observed for total back pain, with significantly higher response rates at week 14 (P≤0.01 across endpoints), sustained over two years.

Early pain response linked to long-term axSpA control

The analysis also examined whether early pain improvement predicted longer-term outcomes. Patients who achieved ≥30% pain reduction at week two or ≥50% at week 14 were more likely to reach stringent disease control targets at week 104, including ASAS partial remission and ASDAS low disease activity or inactive disease.

Although these findings were descriptive, they suggest that early symptom response may help clinicians to identify patients who are more likely to achieve sustained disease control, but some limitations should be considered.

As a post hoc analysis, the study was not designed to establish causality, and associations between early pain improvement and long-term outcomes remain hypothesis-generating, the authors said.

Pain outcomes were patient-reported and therefore subjective, and statistical analyses were not adjusted for multiplicity, increasing the risk of type I error. Additionally, trial populations may not fully reflect real-world clinical practice, they added.

Despite these constraints, the authors concluded that these findings support the rapid, clinically meaningful and sustained impact of upadacitinib on pain across the axSpA spectrum, and that early improvements in pain may serve as a useful indicator of longer-term treatment success, thereby supporting optimal patient care.

Reference Baraliakos X et al. Impact of upadacitinib on reducing pain in patients across the axial spondyloarthritis spectrum: a post hoc analysis of the phase 2/3 SELECT-AXIS studies. Rheumatol Ther 2026;Mar 13:doi:10.1007/s40744-026-00834-5.

This article was originally published by our sister publication Hospital Pharmacy Europe.