A 24-week multicentre, randomized, open-label, parallel-group study comparing the efficacy and safety of ixekizumab vs. fumaric acid esters and methotrexate in patients with moderate-to-severe plaque psoriasis naive to systemic treatment

Abstract

Background: Interleukin-17 antagonists have received a first-line label for moderate-to-severe plaque psoriasis.

Objectives: We conducted the first head-to-head trial between the two most commonly used first-line therapies in Germany, fumaric acid esters (FAEs) and methotrexate, and the interleukin-17A antagonist, ixekizumab.

Methods: Systemic-naive patients were randomized in this parallel-group, active-comparator, open-label, rater-blinded trial (each group n = 54). The primary outcome was the proportion of patients achieving ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) at 24 weeks. Key secondary outcomes included 24-week PASI 90 and 100, static Physician's Global Assessment (sPGA) score of 0 or 1, and Dermatology Life Quality Index (DLQI) score of 0 or 1. Safety events at week 24 were analysed using Fisher's exact test. Missing data were imputed using nonresponder imputation. The trial was registered at ClinicalTrials.gov (NCT02634801) and EudraCT (2015-002649-69).

Results: At week 24, more ixekizumab-treated patients achieved PASI 75 [91% vs. 22% FAEs (P < 0·001) and 70% methotrexate (P = 0·014)], PASI 90 [80% vs. 9% FAEs (P < 0·001) and 39% methotrexate (P < 0·001)] and PASI 100 [41% vs. 4% FAEs (P < 0·001) and 13% methotrexate (P = 0·0041)], as well as sPGA (0,1) and DLQI (0,1).

Conclusions: Ixekizumab was superior in inducing PASI 75/90/100, sPGA (0,1) and DLQI (0,1) responses at week 24 compared with methotrexate and FAEs. Safety profiles for all treatments were consistent with prior studies.

Figure 1

Patient disposition. ^aPatient was randomized in error, and visit 2 was not performed. ^bReason for discontinuation is missing for one patient. ^cReason for discontinuation at visit 11 was documented in error as ‘patient decision’; however, the patient did complete the study up to week 24.

Figure 2

Patients with (a) ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75), (b) PASI 90 and (c) absolute PASI ≤ 3 responses at week 24 for the intention‐to‐treat (ITT) population with nonresponder imputation (NRI). FAE, fumaric acid ester; IXE, ixekizumab; MTX, methotrexate; Nx, number of patients with nonmissing data at week 24; OC, observed cases; Q2W, every 2 weeks; Q4W, every 4 weeks. *P < 0·05 IXE vs. FAEs, ^¶ P < 0·05 IXE vs. MTX, ^‡ddagger; P < 0·05 MTX vs. FAEs. Prespecified P‐values at 12 and 24 weeks are presented (Hochberg adjusted for PASI 75 and PASI 90).

Figure 3

(a) Static Physician's Global Assessment (sPGA) 0 or 1 responses at week 24 for the intention‐to‐treat (ITT) population with baseline sPGA ≥ 3, and (b) Dermatology Life Quality Index (DLQI) 0 or 1 responses at week 24 for the ITT population with nonresponder imputation (NRI). FAE, fumaric acid ester; IXE, ixekizumab; MTX, methotrexate; Q2W, every 2 weeks; Q4W, every 4 weeks. *P < 0·05 IXE vs. FAEs, ^¶ P < 0·05 IXE vs. MTX, ^‡ddagger; P < 0·05 MTX vs. FAEs. Prespecified P‐values at 12 and 24 weeks are presented (Hochberg adjusted).