Efficacy and Safety of Upadacitinib in Patients with Psoriatic Arthritis: 2-Year Results from the Phase 3 SELECT-PsA 1 Study

Abstract

Introduction: Efficacy and safety of the Janus kinase (JAK) inhibitor upadacitinib (UPA) was evaluated in patients with psoriatic arthritis (PsA) through week 104 of the ongoing long-term extension of the phase 3 trial SELECT-PsA 1.

Methods: Exploratory analyses of all primary and secondary endpoints (non-responder imputation and as observed for binary endpoints; mixed-effect model repeated measures and as observed for continuous endpoints), and summary of treatment-emergent adverse events, in patients receiving UPA 15 mg (UPA15) or 30 mg (UPA30) once daily, or adalimumab 40 mg (ADA) every other week, through week 104 are reported.

Results: Of 1704 patients, 25.4% discontinued the study drug by week 104. Proportions of patients achieving ≥ 20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), ≥ 75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), or minimal disease activity (MDA) were maintained through week 104; greater responses by nominal P value were observed with UPA15 and UPA30 versus ADA for ACR20/50/70 and MDA. Mean change from baseline in modified total Sharp/van der Heijde Score (mTSS) was similar across groups and to week 56 results. The safety profile of UPA was generally comparable to ADA and not altered from week 56 data. Rates of serious infection, herpes zoster, anemia, neutropenia, lymphopenia, and elevated creatine phosphokinase remained numerically higher with UPA15 and/or UPA30 versus ADA. Rates of malignancies excluding non-melanoma skin cancer (NMSC), major adverse cardiovascular events, and venous thromboembolism were similar across groups; rates of NMSC were higher with UPA versus ADA. Two deaths were reported with UPA15, one with UPA30, and one with ADA.

Conclusions: In PsA patients, efficacy responses were similar or greater with UPA15 or UPA30 versus ADA through week 104, and inhibition of radiographic progression was maintained. No new safety risks were identified with exposure to UPA through 2 years (week 104).

Clinical trial registration: ClinicalTrials.gov, NCT03104400.

Keywords: 2-year; Adalimumab; Janus kinase (JAK) inhibitor; Non-biologic disease-modifying anti-rheumatic drug (non-bDMARD); Psoriatic arthritis (PsA); SELECT-PsA 1; Safety; Upadacitinib.

© 2022. The Author(s).

Figures

Fig. 1

ACR20, ACR50, and ACR70 through week 104 (NRI). Proportions of patients achieving ACR20 (a), ACR50 (b), or ACR70 (c). Data were analyzed using Cochran–Mantel–Haenszel tests with NRI and are shown as response rates with 95% CIs. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 upadacitinib 15 mg versus adalimumab; #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 upadacitinib 30 mg versus adalimumab; nominal P values are shown and were not multiplicity controlled. ACR20/50/70 ≥ 20%/50%/70% improvement in American College of Rheumatology response criteria, ADA adalimumab, CI confidence interval, EOW every other week, NRI non-responder imputation, QD once daily, UPA upadacitinib

Fig. 2

TJC68 = 0 and SJC66 = 0 through week 104 (NRI). Proportions of patients achieving a TJC68 score of 0 (a) or SJC66 score of 0 (b) in patients with TJC68 > 0 or SJC66 > 0 at baseline, respectively. Data were analyzed using Cochran–Mantel–Haenszel tests with NRI and are shown as response rates with 95% CIs. *P < 0.05, **P < 0.01 upadacitinib 15 mg versus adalimumab; #P < 0.05, ##P < 0.01 upadacitinib 30 mg versus adalimumab; nominal P values are shown and were not multiplicity controlled. ADA adalimumab, CI confidence interval, EOW every other week, NRI non-responder imputation, QD once daily, SJC66 swollen joint count 66, TJC68 tender joint count 68, UPA upadacitinib

Fig. 3

PASI75, PASI90, and PASI100 through week 104 (NRI). Proportions of patients achieving PASI75 (a), PASI90 (b), or PASI100 (c) in patients with psoriasis affecting ≥ 3% of body surface area at baseline. Data were analyzed using Cochran–Mantel–Haenszel tests with NRI and are shown as response rates with 95% CIs. #P < 0.05, ##P < 0.01 upadacitinib 30 mg versus adalimumab; nominal P values are shown and were not multiplicity controlled. ADA adalimumab, CI confidence interval, EOW every other week, NRI non-responder imputation, PASI75/PASI90/PASI100 ≥ 75%/90%/100% improvement in Psoriasis Area Severity Index, QD once daily, UPA upadacitinib

Fig. 4

Resolution of enthesitis (NRI), resolution of dactylitis (NRI), and Modified Total Sharp/van der Heijde Score (MMRM) through week 104. Proportions of patients with resolution of enthesitis (defined as LEI = 0, in patients with baseline LEI > 0) (a), resolution of dactylitis (defined as LDI = 0, in patients with baseline LDI > 0) (b), or mean change from baseline in mTSS (c). Enthesitis and dactylitis data were analyzed using Cochran–Mantel–Haenszel tests with NRI and are shown as response rates with 95% CIs. mTSS data were analyzed using MMRM and are shown as least squares means with 95% CIs. *P < 0.05 upadacitinib 15 mg versus adalimumab; #P < 0.05 upadacitinib 30 mg versus adalimumab; nominal P values are shown and were not multiplicity controlled. ADA adalimumab, CI confidence interval, EOW every other week, LDI Leeds Dactylitis Index, LEI Leeds Enthesitis Index, MMRM mixed-effect model for repeated measures, mTSS modified total Sharp/van der Heijde Score, NRI non-responder imputation, QD once daily, UPA upadacitinib

Fig. 5

Minimal disease activity (NRI), patient’s assessment of pain (MMRM), and Health Assessment Questionnaire-Disability Index (MMRM) through week 104. Proportion of patients achieving MDA (a), mean change from baseline in patient’s assessment of pain (NRS) (b), or mean change from baseline in HAQ-DI (c). MDA data were analyzed using Cochran–Mantel–Haenszel tests with non-responder imputation and are shown as response rates with 95% CIs. Pain and HAQ-DI data were analyzed using a mixed-effect model for repeated measures and are shown as least squares means with 95% CIs. *P < 0.05, **P < 0.01, ***P < 0.001 upadacitinib 15 mg versus adalimumab; #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001 upadacitinib 30 mg versus adalimumab; nominal P values are shown and were not multiplicity controlled. ADA adalimumab, CI confidence interval, EOW every other week, HAQ-DI Health Assessment Questionnaire-Disability Index, MDA minimal disease activity, NRS numeric rating scale, QD once daily, UPA upadacitinib

Fig. 6

Ankylosing Spondylitis Disease Activity Score (MMRM), Bath Ankylosing Spondylitis Disease Activity Index (MMRM), and BASDAI50 (NRI) through week 104. Mean change from baseline in ASDAS (a), mean change from baseline in BASDAI (b), or proportion of patients achieving BASDAI50 (c) in patients with investigator-identified psoriatic spondylitis at baseline. ASDAS and BASDAI data were analyzed using a mixed-effect model for repeated measures and are shown as least squares means with 95% CIs. BASDAI50 data were analyzed using Cochran–Mantel–Haenszel tests with non-responder imputation and are shown as response rates with 95% CIs. *P < 0.05, **P < 0.01 upadacitinib 15 mg versus adalimumab; #P < 0.05, ##P < 0.01, ###P < 0.001 upadacitinib 30 mg versus adalimumab; nominal P-values are shown and were not multiplicity controlled. ADA adalimumab, ASDAS Ankylosing Spondylitis Disease Activity Score, BASDAI Bath Ankylosing Spondylitis Disease Activity Index, BASDAI50 ≥ 50% improvement from baseline in the Bath Ankylosing Spondylitis Disease Activity Index, CI confidence interval, EOW every other week, QD once daily, UPA upadacitinib

Fig. 7

Exposure-adjusted event rates of treatment-emergent adverse events through week 104. Number of events are provided in Supplementary Table 5. aIncludes placebo patients that switched to upadacitinib. bOpportunistic infections excluding TB and herpes zoster. cMACE defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. dVTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE) (fatal and non-fatal). ADA adalimumab, CI confidence interval, CPK creatine phosphokinase, EAER exposure-adjusted event rate, EOW every other week, GI gastrointestinal, IBD inflammatory bowel disease, MACE major adverse cardiovascular events, NMSC non-melanoma skin cancer, PBO placebo, PY patient years, QD once daily, TB tuberculosis, UPA upadacitinib, VTE venous thromboembolism