Sustained improvements in physical function, quality of life, and work productivity with ixekizumab in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor-inhibitors: 3-year results from spirit-P2 trial

Abstract

Background: Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets IL-17A, has shown improvements compared to placebo (PBO) not only in disease activity but also in various patient-reported outcomes (PROs) assessing physical function, quality of life (QoL), and work productivity in PsA patients treated for 24 weeks and sustained up to 52 weeks.1, 2

Objectives: To report the effects of treatment with IXE on these PROs after up to 3 years of treatment.

Methods: In SPIRIT-P2 (NCT02349295), a Phase 3 trial, 363 adult patients with active PsA and prior inadequate response or intolerance to 1 or 2 TNF inhibitors (TNFis) were randomized 1:1:1 to IXE 80 mg every 4 weeks (IXEQ4W; N=122) or every 2 weeks (IXEQ2W; N=123), or PBO (N=118) in the double-blind treatment period (Weeks 0-24). Both IXE regimens had a starting dose of 160 mg. Results are reported from a subset of the intent-to-treat population who were randomized to IXE at baseline (Week 0). The following PROs were assessed during Weeks 0-156: HAQ-DI (minimally clinically important difference [MCID] an improvement ≥0.35), medical outcomes survey Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS), European Quality of Life 5 Dimensions Visual Analog Scale (EQ-5D VAS), and Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP; absenteeism, presenteeism, work productivity, and activity impairment). Missing values were imputed by observed analysis and modified baseline observation carried forward (mBOCF) for continuous data or by modified non-responder imputation (mNRI) for categorical data.

Results: Mean baseline scores for SF-36 (PCS and MCS), EQ-5D VAS, and WPAI-SHP (Figure 1) and HAQ-DI (mean [SD]: IXEQ4W=1.2 [0.6]; IXEQ2W=1.2 [0.6]), indicated impaired physical function and QoL. The percentage of patients of who completed 156 weeks of the study in IXEQ4W and IXEQ2W arms were 57.4% (n=70) and 44.7% (n=55), respectively. Patients receiving IXE treatment up to 3 years reported sustained improvements in SF-36 (PCS and MCS), EQ-5D VAS, and WPAI-SHP (presenteeism, work productivity, and activity impairment) (Figure 1). Observed HAQ-DI mean change from baseline in IXEQ4W: -0.46 (0.62) and IXEQ2W: -0.48 (0.55). The percentage of IXE treated patients achieving MCID for HAQ-DI (improvement ≥0.35) was sustained at 3 years (Figure 2).