Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: results from two phase 3 studies

Abstract

Background: The objective of this post-hoc analysis was to assess the efficacy and safety of upadacitinib in psoriatic arthritis (PsA) patients with axial involvement.

Methods: Post-hoc analysis of SELECT-PsA 1 and SELECT-PsA 2 in patients randomized to upadacitinib 15 mg (UPA15), placebo (switched to UPA15 at week 24), or adalimumab 40 mg (ADA; SELECT-PsA 1 only). Axial involvement was determined by investigator judgement (yes or no; based on the totality of available clinical information, such as duration and characteristics of back pain, age of onset, and previous lab investigations and imaging, if available) alone, or investigator judgement and patient-reported outcome (PRO)-based criteria (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4 and BASDAI Q2 ≥ 4). Efficacy outcomes that describe axial disease activity, including BASDAI endpoints, such as change from baseline in the overall BASDAI score or proportion of patients achieving BASDAI50 (≥ 50% improvement from baseline), as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) endpoints, such as mean change from baseline in overall ASDAS or proportion of patients achieving ASDAS inactive disease or low disease activity, were evaluated at weeks 12, 24, and 56, with nominal P-values shown. Treatment-emergent adverse events (TEAEs) are summarized through week 56.

Results: 30.9% of patients in SELECT-PsA 1 and 35.7% in SELECT-PsA 2 had axial involvement by investigator judgement alone; 22.6% (SELECT-PsA 1) and 28.6% (SELECT-PsA 2) had axial involvement by investigator judgement and PRO-based criteria. Greater proportions of patients achieved BASDAI50 with UPA15 versus placebo using either criterion, and versus ADA using investigator judgement alone, at week 24 in SELECT-PsA 1 (investigator alone: UPA15, 59.0%, placebo, 26.9%, P < 0.0001, ADA, 44.1%, P = 0.015; investigator and PRO-based: UPA15, 60.4%, placebo, 29.3%, P < 0.0001, ADA, 47.1%, P = 0.074), with comparable findings in SELECT-PsA 2. Similar results were observed with UPA15 for additional BASDAI and ASDAS endpoints at weeks 12 and 24, with improvements maintained at week 56. Rates of TEAEs were generally similar across sub-groups irrespective of axial involvement status.

Conclusions: PsA patients with axial involvement determined by predefined criteria showed greater BASDAI and ASDAS responses with UPA15 versus placebo, and numerically similar/greater responses versus ADA. Safety results were generally comparable between patients with or without axial involvement.

Trial registration: ClinicalTrials.gov: SELECT-PsA 1, NCT03104400; SELECT-PsA 2, NCT0310437.

Keywords: Adalimumab; Ankylosing Spondylitis Disease Activity Score (ASDAS); Axial involvement; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); Janus kinase (JAK) inhibitor; Psoriatic arthritis (PsA); Safety; Upadacitinib.

Fig. 1

Proportion of PsA Patients With Axial Involvement Defined by Investigator Judgement Alone or Investigator Judgement and PRO-Based Criteria. ^aSub-groups shown include the following treatments from SELECT-PsA 1: placebo, adalimumab, and upadacitinib 15 mg; upadacitinib 30 mg is excluded. ^bSub-groups shown include the following treatments from SELECT-PsA 2: placebo and upadacitinib 15 mg; upadacitinib 30 mg is excluded. ADA, adalimumab; bDMARD, biologic disease-modifying antirheumatic drug; IR, inadequate response; PBO, placebo; PRO, patient-reported outcome; PsA, psoriatic arthritis; UPA, upadacitinib

Fig. 2

Mean Change From Baseline in Overall BASDAI and Modified BASDAI (Excluding Question 3) Scores, and Proportion of Patients Achieving BASDAI50, at Weeks 12 and 24 From SELECT-PsA 1 (non-bDMARD-IR) and SELECT-PsA 2 (bDMARD-IR). Mean change from baseline in the overall BASDAI score (A) or modified BASDAI (excluding question 3—How would you describe the overall level of pain/swelling in joints other than neck, back, or hips you have had?) score (C) at weeks 12 and 24 for PsA patients with axial involvement defined by investigator judgement alone or investigator judgement and PRO-based criteria treated with placebo, upadacitinib 15 mg QD, or adalimumab 40 mg EOW from SELECT-PsA 1. Mean change from baseline in overall BASDAI (B) or modified BASDAI (D) at weeks 12 and 24 for PsA patients with axial involvement defined by either criterion treated with placebo or upadacitinib 15 mg QD from SELECT-PsA 2. Proportions of PsA patients with axial involvement defined by investigator judgement alone or investigator judgement and PRO-based criteria that achieved BASDAI50 at weeks 12 and 24 treated with placebo, upadacitinib 15 mg QD, or adalimumab 40 mg EOW from SELECT-PsA 1 (E) or with placebo or upadacitinib 15 mg QD from SELECT-PsA 2 (F). Overall BASDAI and modified BASDAI were analyzed using mixed-effect model for repeated measures and are shown as least squares means with 95% CIs. BASDAI50 was analyzed using Cochran-Mantel–Haenszel tests with non-responder imputation and shown as response rates with 95% CIs. ****P < 0.0001, ***P < 0.001, *P < 0.05 upadacitinib 15 mg versus placebo; ^#P < 0.05, upadacitinib 15 mg versus adalimumab; nominal P values are shown and were not multiplicity controlled. ADA, adalimumab; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASDAI50, ≥ 50% improvement from baseline in BASDAI; bDMARD, biologic disease-modifying antirheumatic drug; CI, confidence interval; EOW, every other week; IR, inadequate response; PBO, placebo; PRO, patient-reported outcome; PsA, psoriatic arthritis; QD, once daily; UPA, upadacitinib

Fig. 3

Mean Change From Baseline in ASDAS Scores, and Proportion of Patients Achieving ASDAS Inactive Disease (ID) and ASDAS Low Disease Activity (LDA), at Weeks 12 and 24 From SELECT-PsA 1 (non-bDMARD-IR) and SELECT-PsA 2 (bDMARD-IR). Mean change from baseline in ASDAS (CRP) scores at weeks 12 and 24 for PsA patients with axial involvement defined by investigator judgement alone or investigator judgement and PRO-based criteria treated with placebo, upadacitinib 15 mg QD, or adalimumab 40 mg EOW from SELECT-PsA 1 (A) or with placebo or upadacitinib 15 mg QD from SELECT-PsA 2 (B). Proportions of PsA patients with axial involvement defined by investigator judgement alone or investigator judgement and PRO-based criteria treated with placebo, upadacitinib 15 mg QD, or adalimumab 40 mg EOW that achieved ASDAS ID (C) or ASDAS LDA (E) at weeks 12 and 24 from SELECT-PsA 1. Proportions of PsA patients with axial involvement defined by either criterion treated with placebo or upadacitinib 15 mg QD that achieved ASDAS ID (D) or ASDAS LDA (F) at weeks 12 and 24 from SELECT-PsA 2. ASDAS ID defined as score < 1.3; LDA defined as score < 2.1. ASDAS was analyzed using mixed-effect model for repeated measures and are shown as least squares means with 95% CIs. ASDAS ID and ASDAS LDA were analyzed using Cochran-Mantel–Haenszel tests with non-responder imputation and are shown as response rates with 95% CIs. ****P < 0.0001, ***P < 0.001, **P < 0.01, upadacitinib 15 mg versus placebo; ^##P < 0.01, upadacitinib 15 mg versus adalimumab; nominal P values are shown and were not multiplicity controlled. ADA, adalimumab; ASDAS, Ankylosing Spondylitis Disease Activity Score; bDMARD, biologic disease-modifying antirheumatic drug; CI, confidence interval; EOW, every other week; ID, inactive disease; IR, inadequate response; LDA, low disease activity; PBO, placebo; PRO, patient-reported outcome; PsA, psoriatic arthritis; QD, once daily; UPA, upadacitinib