IL-17 Inhibitors Make Clear Skin A Reachable Goal in Severe Psoriasis

Bachelez H. Comment: Interleukin-17 inhibition: a route to psoriasis clearance? The Lancet.Online: 10 June 2015. DOI: 10.1016/S0140-6736(15)60857-1

Griffiths CEM, Reich K, Lebwohl M, et al, for the UNCOVER-2 UNCOVER-3 investigators. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. The Lancet. Online: 10 June 2015. DOI: 10.1016/S0140-6736(15)60125-8

Interleukin-17 (IL-17) inhibitors may offer complete or almost complete skin clearance for many patients with severe psoriasis. Even now, the goal of 90% skin clearance is a “reachable” goal, and could replace 75%, says an editorial by Hervé Bachelez in The Lancet.

Clear skin is qualitatively different from almost-clear skin. Significantly more patients with clear skin than almost-clear skin reported no effect of psoriasis on their quality of life. “Residual skin disease has a substantial effect on patient-reported outcomes, and attaining clear skin should be the new treatment goal for all patients with psoriasis,” the investigators wrote.

In a pair of 12-week Phase 3 studies, 90% and 70% of patients given ixekizumab every 2 weeks reached psoriasis area and severity index (PASI) 75 and 90, respectively.

Together with the recent phase 3 trial of secukinumab, the UNCOVER-2 and -3 trials “provide a second set of robust evidence that blocking interleukin 17 in severe psoriasis leads to superior efficacy over etanercept,” Bachelez writes. (See Secukinumab Effective for Psoriasis.)

The benefit/risk ratio of ixekizumab in these 12-week studies is “appealing,” he writes. Longer-term trials are ongoing, but large post-marketing registries of IL-17 inhibitors will be required to give the needed long-term data in real-world populations. Many patients with severe psoriasis are excluded from clinical trials, he notes. The predicted risk of IL-17 inhibitors are fungal and bacterial infections, and a higher incidence of infection was found in ixekizumab than etanercept. Non-invasive Candida species were found in this trial, and also in the secukinumab trial. Another concern was one new case and one worsening case of Crohn’s disease in the high-dose ixekizumab group.

The 2 trials, with a total of 2,570 patients, were randomized to etanercept, 2 dosing schedules of ixekizumab, and placebo. Primary end points were PASI 75 and static physician global assessment score 0 or 1.

UNCOVER-2

Etanercept

Ixekizumab every 2 weeks

Ixekizumab every 4 weeks

Placebo

sPGA

36%

83%

73%

2.4%

PASI 75

42%

90%

77%

2.4%

sPGA = static physician global assessment

PASI 75 = psoriasis area and severity index 75% improvement

(See The IL-17 Superfamily: What Future for PsA?