Efficacy of upadacitinib in subgroups of patients with axial spondyloarthritis with early versus established disease

Abstract

Objectives: Early disease activity control with targeted therapies may improve long-term outcomes in axial spondyloarthritis (axSpA). Here, we evaluated the efficacy of upadacitinib in patients with axSpA with shorter versus longer symptom durations.

Methods: SELECT-AXIS 1 and 2 studies enrolled patients with radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) naïve to biologic disease-modifying antirheumatic drugs (bDMARD-naïve) and with an intolerance or inadequate response to bDMARD therapy. Patients were stratified by symptom duration (nr-axSpA: early vs established (≤2 vs >2 years=Assessment of SpondyloArthritis international Society (ASAS) definition) and shorter vs longer (≤5 vs >5 years); r-axSpA: ≤5 vs >5 years). Efficacy endpoints assessed through week 14 included the proportion of patients achieving Axial Spondyloarthritis Disease Activity Score and ASAS40 responses, among others. Across all endpoints, the efficacy of upadacitinib versus placebo was assessed by relative risk (RR), and the placebo-adjusted effect of upadacitinib between shorter versus longer symptom duration was assessed by the RR ratio.

Results: At week 14, better responses were observed in patients treated with upadacitinib in all endpoints assessed compared with placebo, regardless of symptom duration. When comparing patients with early/shorter versus established/longer symptom durations, for all measures assessed, no statistically significant differences were observed except for the change from baseline in high-sensitivity C-reactive protein in the nr-axSpA group, with a better response in early disease (difference -8.2, 95% CI -14.9 to -1.6).

Conclusion: Regarding short-term outcomes, both subgroups of patients (shorter axSpA symptom duration (≤2 years) and longer symptom duration (>2 years)) achieved comparable results when treated with upadacitinib.

Trial registration number: NCT03178487 (SELECT-AXIS 1) and NCT04169373 (SELECT-AXIS 2).

Keywords: Antirheumatic Agents; Axial Spondyloarthritis; Patient Reported Outcome Measures.

Figure 1. Proportion of patients achieving ASDAS LDA, ASDAS ID, ASDAS CII and ASDAS MI at week 14 with early versus established (≤2 years vs >2 years) nr-axSpA as defined by the ASAS consensus definition, and nr-axSpA with short versus long (≤5 years vs >5 years) symptom duration. *RR (95% CI) UPA versus PBO. †RRR (95% CI) early/short versus established/long disease/symptom duration. ASAS, Assessment of Spondyloarthritis international Society; ASDAS, Axial Spondyloarthritis Disease Activity Score; CII, clinically important improvement; ID, inactive disease; LDA, low disease activity; MI, major improvement; nr-axSpA, non-radiographic axial spondyloarthritis; PBO, placebo; QD, once daily; RR, relative risk; RRR, RR ratio; UPA, upadacitinib.

Figure 2. Proportion of patients achieving ASAS40, and mean change from baseline in patient assessment of total back pain and hsCRP at week 14 with early versus established (≤2 years vs >2 years) nr-axSpA as defined by the ASAS consensus definition, and nr-axSpA with short versus long (≤5 years vs >5 years) symptom duration. *RR (95% CI) UPA versus PBO. †RRR (95% CI) early/short versus established/long disease/symptom duration. ‡Between-group difference (95% CI) UPA versus PBO. §Between-treatment group difference (95% CI) early/short versus established/long disease. ASAS, Assessment of SpondyloArthritis international Society; ASAS40, 40% improvement in three out of the four ASAS domains without worsening in the remaining domain; hsCRP, high-sensitivity C-reactive protein; nr-axSpA, non-radiographic axial spondyloarthritis; PBO, placebo; QD, once daily; RR, relative risk; RRR, RR ratio; UPA, upadacitinib.

Figure 3. Proportion of patients achieving BASDAI50, and mean change from baseline in BASFI, BASMI and ASAS HI at week 14 with early versus established (≤2 years vs >2 years) nr-axSpA as defined by the ASAS consensus definition, and nr-axSpA with short versus long (≤5 years vs >5 years) symptom duration. *RR (95% CI) UPA versus PBO. †RRR (95% CI) early/short versus established/long disease/symptom duration. ‡Between-group difference (95% CI) UPA versus PBO. §Between-treatment group difference (95% CI) early/short versus established/long disease. ASAS, Assessment of SpondyloArthritis international Society; ASAS HI, ASAS Health Index; BASDAI50, ≥50% improvement in Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index; BASMI, Bath Ankylosing Spondylitis Metrology Index; nr-axSpA, non-radiographic axial spondyloarthritis; PBO, placebo; QD, once daily; RR, relative risk; RRR, RR ratio; UPA, upadacitinib.

Figure 4. Mean change from baseline in MRI SPARCC (SIJs and spine) at week 14 in patients with early versus established (≤2 years vs >2 years) nr-axSpA as defined by the ASAS consensus definition, and nr-axSpA with short versus long (≤5 years vs >5 years) symptom duration. *Between-group difference (95% CI) UPA versus PBO. †Between-treatment group difference (95% CI) early/short versus established/long disease. ASAS, Assessment of SpondyloArthritis international Society; nr-axSpA, non-radiographic axial spondyloarthritis; PBO, placebo; QD, once daily; SIJ, sacroiliac joint; SPARCC, SpondyloArthritis Research Consortium of Canada; UPA, upadacitinib.