Effects of upadacitinib on enthesitis in patients with psoriatic arthritis: a post hoc analysis of SELECT-PsA 1 and 2 trials

Abstract

Objectives: To characterize the effect of upadacitinib 15 mg once daily (UPA15) on enthesitis in patients with PsA from the SELECT-PsA Phase 3 trials.

Methods: Patients with an inadequate response/intolerance to one or more non-biologic DMARD (SELECT-PsA 1) or one or more biologic DMARD (SELECT-PsA 2) received UPA15, adalimumab 40 mg every other week or placebo (weeks 0-24) switched to UPA15 (week 24 onward). The Leeds Enthesitis Index (LEI) and Spondyloarthritis Research Consortium of Canada (SPARCC) index were used to assess improvement in enthesitis, enthesitis resolution, maintenance of enthesitis resolution and protection from enthesitis development through week 56.

Results: Data from 639 patients receiving UPA15 and 635 patients receiving placebo (including 317 patients who switched from placebo to UPA15) were analysed. UPA15 led to higher rates of enthesitis resolution vs placebo at week 24 (LEI: 59.8% vs 38.0%; SPARCC index: 50.6% vs 31.5%, respectively) and greater improvements in the LEI (-1.7 vs -1.0) and SPARCC index (-3.4 vs -1.9); improvements were maintained through week 56. Improvements were observed after 12 weeks of UPA15 treatment. Over 90% of patients without enthesitis (LEI = 0) at baseline receiving UPA15 were enthesitis-free at week 56, and UPA15 prevented recurrence of enthesitis at week 56 in >80% of patients with enthesitis at baseline who achieved resolution (LEI = 0) at week 24.

Conclusions: UPA15 is associated with a comprehensive improvement in enthesitis, with improvements observed after 12 weeks of treatment. Additionally, treatment with UPA15 was associated with maintaining an enthesitis-free state after resolution and protection against new-onset enthesitis.

Trial registration: ClinicalTrials.gov identifiers: NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2).

Keywords: Janus kinase inhibitor; entheses; enthesitis; pain; psoriatic arthritis; upadacitinib.

Figure 1.

Resolution of enthesitis over time in patients with enthesitis at baseline (A) LEI and (B) SPARCC index (as observed). Error bars represent 95% CIs. All P-values are nominal. LEI: Leeds Enthesitis Index; QD: once daily; SPARCC: Spondyloarthritis Research Consortium of Canada; UPA: upadacitinib; W: week

Figure 2.

Change from baseline in (A) LEI and (B) SPARCC index in patients with baseline enthesitis (MMRM). Error bars represent 95% CIs. All P-values are nominal. LEI: Leeds Enthesitis Index; LS: least squares; MMRM: mixed model for repeated measures; QD: once daily; SPARCC: Spondyloarthritis Research Consortium of Canada; UPA: upadacitinib; W: week

Figure 3.

Maintenance of enthesitis resolution in patients with resolution at week 24 and baseline enthesitis, (A) LEI and (B) SPARCC index (NRI). LEI: Leeds Enthesitis Index; NRI: non-responder imputation; QD: once daily; SPARCC: Spondyloarthritis Research Consortium of Canada; UPA: upadacitinib

Figure 4.

Residual enthesitis sites at week 24 in patients without resolution of enthesitis, (A) LEI and (B) SPARCC index (NRI). Error bars represent 95% CIs. LEI: Leeds Enthesitis Index; NRI: non-responder imputation; QD: once daily; SPARCC: Spondyloarthritis Research Consortium of Canada; UPA: upadacitinib

Figure 5.

Protection from enthesitis development over time in patients without enthesitis at baseline (as observed). Error bars represent 95% CIs. All P-values are nominal. LEI: Leeds Enthesitis Index; QD: once daily; UPA: upadacitinib; W: week

Figure 6.

Patient’s assessment of pain in patients with enthesitis at baseline (MMRM). Error bars represent 95% CIs. All P-values are nominal. EOW: every other week; LS: least squares; MMRM: mixed model for repeated measures; QD: once daily; SPARCC: Spondyloarthritis Research Consortium of Canada; UPA: upadacitinib; W: week