Direct comparison of risankizumab and fumaric acid esters in systemic therapy-naïve patients with moderate-to-severe plaque psoriasis: a randomized controlled trial

Abstract

Background: Fumaric acid esters (FAEs; Fumaderm^® ) are the most frequently prescribed first-line systemic treatment for moderate-to-severe plaque psoriasis in Germany. Risankizumab (Skyrizi^® ) is a humanized IgG1 monoclonal antibody that specifically binds to the p19 subunit of interleukin 23.

Objectives: To compare risankizumab treatment to FAEs in patients with psoriasis.

Methods: This phase III randomized, active-controlled, open-label study with blinded assessment of efficacy was conducted in Germany. Patients were randomized (1 : 1) to subcutaneous risankizumab 150 mg (weeks 0, 4 and 16) or oral FAEs at increasing doses from 30 mg daily (week 0) up to 720 mg daily (weeks 8-24). Enrolled patients were adults naïve to and candidates for systemic therapy, with chronic moderate-to-severe plaque psoriasis. Phototherapy was not allowed within 14 days before or during the study.

Results: Key efficacy endpoints were met at week 24 for risankizumab (n = 60) vs. FAEs (n = 60) (P < 0·001): achievement of a ≥ 90% improvement in Psoriasis Area and Severity Index (PASI; primary endpoint 83·3% vs. 10·0%), ≥ 100% improvement in PASI (50·0% vs. 5·0%), ≥ 75% improvement in PASI (98·3% vs. 33·3%), ≥ 50% improvement in PASI (100% vs. 53·3%) and a Static Physician's Global Assessment of clear/almost clear (93·3% vs. 38·3%). The rates of gastrointestinal disorders, flushing, lymphopenia and headache were higher in the FAE group. One patient receiving risankizumab reported a serious infection (influenza, which required hospitalization). There were no malignancies, tuberculosis or opportunistic infections in either treatment arm.

Conclusions: Risankizumab was found to be superior to FAEs, providing earlier and greater improvement in psoriasis outcomes that persisted with continued treatment, and more favourable safety results, which is consistent with the known safety profile. No new safety signals for risankizumab or FAEs were observed.

Figure 1

Study design. FAEs, fumaric acid esters (oral formulation); PASI 90, ≥ 90% improvement from baseline in Psoriasis Area and Severity Index; RZB, risankizumab; SC, subcutaneously. ^aIf tolerability allowed.

Figure 2

Study flowchart. AE, adverse event; FAEs, fumaric acid esters. ^aPrimary reason.

Figure 3

Achievement of Psoriasis Area and Severity Index (PASI) across 24 weeks of treatment. (a) Fifty per cent or more improvement in PASI from baseline (PASI 50), (b) ≥ 75% improvement in PASI from baseline (PASI 75), (c) ≥ 90% improvement in PASI from baseline (PASI 90; primary efficacy endpoint) and (d) 100% improvement in PASI from baseline (PASI 100). Intention‐to‐treat population, nonresponder imputation. *P < 0·001 and ^† P < 0·05 vs. fumaric acid esters (oral formulation; FAEs). RZB, risankizumab.

Figure 4

Achievement of static Physician’s Global Assessment (sPGA) across 24 weeks of treatment. (a) sPGA 0/1 and (b) sPGA 0. Intention‐to‐treat population, nonresponder imputation. *P < 0·001; ^† P < 0·05 and ^‡ P = 0·01 vs. fumaric acid esters (oral formulation; FAEs). RZB, risankizumab.

Figure 5

Psoriasis Area and Severity Index (PASI) efficacy outcomes. Intention‐to‐treat population. *P < 0·001 and ^‡ P = 0·01 vs. fumaric acid esters (oral formulation; FAEs). (a) Mean percentage improvement from baseline in overall PASI (LOCF) and (b–d) proportion of patients achieving PASI < 1, ≤ 3 and ≤ 5 (NRI), respectively. P‐values calculated from ANCOVA with baseline value and treatment in the model. LOCF, last observation carried forward; NRI, nonresponder imputation; RZB, risankizumab.

Figure 6

Improvement from baseline in palmoplantar psoriasis, scalp and nail outcomes. Mean percentage improvement from baseline in (a) Palmoplantar Psoriasis Area Severity Index (PPASI), (b) Psoriatic Scalp Severity Index (PSSI) and (c) Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPSI). Intention‐to‐treat population, last observation carried forward (LOCF). *P < 0·001 and ^† P < 0·05 vs. fumaric acid esters (oral formulation; FAEs). RZB, risankizumab.