Efficacy and Safety of Ixekizumab in Patients with Psoriatic Arthritis and Inadequate Response to TNF Inhibitors: 3-Year Follow-Up (SPIRIT-P2)

Abstract

Purpose: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A. The objective of this study was to assess the long-term efficacy and safety (to week 156) of ixekizumab in patients with active psoriatic arthritis and inadequate response or intolerance to one or two tumor necrosis factor inhibitors.

Methods: In the SPIRIT-P2 study (ClinicalTrials.gov ID: NCT02349295), patients were randomized to placebo or ixekizumab 80 mg every 4 weeks (IXE Q4W) or every 2 weeks (IXE Q2W) following a 160-mg starting dose. During the extension period (weeks 24-156), patients maintained their original ixekizumab dose, and placebo patients received IXE Q4W or IXE Q2W (1:1). Exposure-adjusted incidence rates (IRs) per 100 patient-years (PY) are presented.

Results: Of 363 patients enrolled in the study, 310 entered the extension period. In all patients treated with IXE Q4W and IXE Q2W at week 0, responses persisted to week 156. At week 156, clinical responses (observed) in patients treated with IXE Q4W and IXE Q2W were assessed [American College of Rheumatology (ACR) response criteria and minimal disease activity (MDA) criteria]: 84 and 85% showed 20% improvement (ACR20); 60 and 58% showed 50% improvement (ACR50); 35 and 47% showed 70% improvement (ACR70), respectively; and 48 and 54% showed MDA. Placebo patients re-randomized to ixekizumab also demonstrated sustained efficacy, as measured by ACR and MDA responses. In the All Ixekizumab Exposure Safety Population (n = 337), with 644 PY of ixekizumab exposure, treatment-emergent adverse events (TEAEs) were reported by 286 patients (44.4 IR). The most common TEAEs were upper respiratory tract infection (9.80 IR), nasopharyngitis (8.2 IR), sinusitis (6.2 IR), and bronchitis (4.5 IR). Serious adverse events were reported by 42 (6.5 IR) patients (included 3 deaths and 10 infections).

Conclusion: In this 156-week study of ixekizumab, improvements in signs and symptoms of psoriatic arthritis and the safety profile remained consistent with those in previous reports.

Trial registration: ClinicalTrials.gov identifier: NCT02349295.

Keywords: Efficacy; Interleukin-17A; Ixekizumab; Psoriatic arthritis; Safety.

Figures

Fig. 1

American College of Rheumatology (ACR) and minimal disease activity (MDA) responses up to week 156, as observed and modified nonresponder imputation (mNRI). Intent-to-treat population randomized to ixekizumab at week 0. Starting at week 32, and at all subsequent visits during the extension period, patients were discontinued from study treatment if they failed to demonstrate ≥ 20% improvement from baseline in tender (TJC) and swollen (SJC) joint counts. MDA defined as achieving five of the seven following MDA components: TJC ≤ 1, SJC ≤ 1, Psoriasis Area and Severity Index ≤ 1 or body surface area ≤ 3%, patient pain visual analog scale (VAS) ≤ 15, patient global disease activity VAS ≤ 20, Health Assessment Questionnaire–Disability Index ≤ 0.5, and ≤ 1 tender entheseal points. ACR20/50/70 ACR response criteria improvement of 20, 50, or 70%, respectively, IXE Q2W ixekizumab 80 mg every 2 weeks, IXE Q4W ixekizumab 80 mg every 4 weeks

Fig. 2

Enthesitis, dactylitis, and nail psoriasis up to week 156 [observed and modified baseline observation carried forward (mBOCF)]. Intent-to-treat population randomized to ixekizumab at week 0. Leeds Enthesitis Index (LEI) and Leeds Dactylitis Index–Basic (LDI-B) were assessed in patients with baseline LEI score > 0 and LDI-B score > 0, respectively. Nail Area Psoriasis Severity Index (NAPSI) was assessed in patients with fingernail psoriasis at baseline. Starting at week 32, and all subsequent visits during the extension, patients not demonstrating ≥ 20% improvement from baseline in both tender and swollen joint counts were discontinued . IXE Q2W ixekizumab 80 mg every 2 weeks, IXE Q4W ixekizumab 80 mg every 4 weeks

Fig. 3

Psoriasis Area and Severity Index (PASI) responses (observed and with mNRI). Intent-to-treat population randomized to ixekizumab at week 0 with ≥ 3% body surface area of disease at baseline. Starting at week 32, and at all subsequent visits during the extension period, patients were discontinued from study treatment if they failed to demonstrate ≥ 20% improvement from baseline in tender and swollen joint counts. IXE Q2W ixekizumab 80 mg every 2 weeks, IXE Q4W ixekizumab 80 mg every 4 weeks, PASI 75/90/100 75/90/100% improvement from baseline on the PASI, respectively

Fig. 4

Health Assessment Questionnaire-Disability Index (HAQ-DI) minimal clinically important difference (MCID; observed and with mNRI) and HAQ-DI change from baseline (observed and mBOCF) up to week 156. Intent-to-treat population randomized to ixekizumab at week 0. MCID was assessed in patients with baseline HAQ-DI ≥ 0.35. Starting at week 32, and all subsequent visits during the extension period, patients not demonstrating ≥ 20% improvement from baseline in tender and swollen joint counts were discontinued. IXE Q2W ixekizumab 80 mg every 2 weeks, IXE Q4W ixekizumab 80 mg every 4 weeks