Efficacy and Safety of Mirikizumab (LY3074828) in the Treatment of Moderate-to-severe Plaque Psoriasis

Results From a Randomized Phase II Study

K. Reich; P. Rich; C. Maari; R. Bissonnette; C. Leonardi; A. Menter; A. Igarashi; P. Klekotka; D. Patel; J. Li; J. Tuttle; M. Morgan-Cox; E. Edson-Heredia; S. Friedrich; K. Papp; on behalf of the AMAF investigators

Disclosures

The British Journal of Dermatology. 2019;181(1):88-95. 

In This Article

Abstract and Introduction

Abstract

Background: Inhibiting interleukin (IL)-23 in patients with psoriasis has demonstrated high levels of skin clearance.

Objectives: To investigate, in a phase II (AMAF; NCT02899988), multicentre, double-blind trial, the efficacy and safety of three doses of mirikizumab (LY3074828), a p19-directed IL-23 antibody, vs. placebo in patients with moderate-to-severe plaque psoriasis.

Methods: Adult patients were randomized 1 : 1 : 1 : 1 to receive placebo (n = 52), mirikizumab 30 mg (n = 51), mirikizumab 100 mg (n = 51) or mirikizumab 300 mg (n = 51) subcutaneously at weeks 0 and 8. The primary objective was to evaluate the superiority of mirikizumab over placebo in achieving a 90% improvement in the Psoriasis Area and Severity Index (PASI 90) response at week 16. Comparisons were done using logistic regression analysis with treatment, geographical region and previous biological therapy in the model. Missing data were imputed as nonresponses.

Results: Ninety-seven per cent of patients completed the first 16 weeks of the study. The primary end point was met for all mirikizumab dose groups vs. placebo, with PASI 90 response rates at week 16 of 0%, 29% (P = 0·009), 59% (P < 0·001) and 67% (P < 0·001) for patients receiving placebo, and mirikizumab 30 mg, 100 mg and 300 mg, respectively. There were two (1%) serious adverse events in mirikizumab-treated patients vs. one (2%) in a placebo-group patient.

Conclusions: At week 16, 67% of patients treated with mirikizumab 300 mg at 8-week intervals achieved PASI 90. The percentage of patients reporting at least one treatment-emergent adverse event was similar among patients treated with placebo or mirikizumab.

The importance of T helper cell 17-related cytokines in the pathogenesis of psoriasis has become increasingly clear in the last decade, with therapies targeting interleukin (IL)-17 and IL-23 resulting in a higher proportion of patients achieving higher efficacy levels than previously described with other biological therapies.[1–9] Ustekinumab was one of the first biologics to target this pathway. However, as ustekinumab binds to the shared p40 subunit, IL-12 is inhibited in addition to IL-23.[4,6] Gene expression patterns in lesions from patients with psoriasis, as well as studies of mouse models of psoriasis, point to IL-23, and not IL-12, as being the more critical cytokine in psoriasis pathogenesis.[10–12] Recently, several biological therapies targeting the p19 subunit of IL-23 have resulted in high Psoriasis Area and Severity Index (PASI) response rates with good safety profiles.[5,7–9]

Mirikizumab (LY3074828), a humanized IgG4-variant monoclonal antibody that binds to the p19 subunit of IL-23 and does not bind IL-12, was previously shown in a phase I study to improve PASI score in patients with plaque psoriasis.[13] We evaluated the week-16 efficacy and safety of three dosing regimens of mirikizumab vs. placebo in a phase II, randomized, multicentre, double-blind trial (AMAF; NCT02899988) of patients with moderate-to-severe plaque psoriasis.

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