Sustained response with ixekizumab treatment of moderate-to-severe psoriasis with scalp involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2, UNCOVER-3)

Abstract

Background: Scalp is a frequently affected and difficult-to-treat area in psoriasis patients.

Objective: We assessed the efficacy of ixekizumab in the treatment of patients with scalp psoriasis over 60 weeks using the Psoriasis Scalp Severity Index (PSSI).

Methods: In three Phase 3, multicenter, double-blind, placebo-controlled trials, patients with moderate-to-severe psoriasis in UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224) and UNCOVER-3 (N = 1346) were randomized to subcutaneous 80 mg ixekizumab every two weeks (Q2W) or every four weeks (Q4W) after a 160 mg starting dose, or placebo through Week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg bi-weekly etanercept through Week 12. Patients entering the open-label long-term extension (LTE) (UNCOVER-3) received ixekizumab Q4W; UNCOVER-1 and UNCOVER-2 included a blinded maintenance period in which static physician global assessment (sPGA) 0/1 responders were re-randomized to placebo, ixekizumab Q4W, or 80 mg ixekizumab every 12 weeks (Q12W) through Week 60.

Results: In patients with moderate-to-severe psoriasis with baseline scalp involvement, PSSI 90 and 100 were achieved at Week 12 in higher percentages of patients treated with ixekizumab Q2W (81.7% and 74.6%) or ixekizumab Q4W (75.6% and 68.9%) compared with patients treated with placebo (7.6% and 6.7%; p < .001 each ixekizumab arm versus placebo) or etanercept (55.5% and 48.1%; p < .001 each ixekizumab arm versus etanercept). These outcomes were maintained through Week 60 of the maintenance (UNCOVER-1 and UNCOVER-2) and LTE (UNCOVER-3) period in patients who continued on ixekizumab Q4W.

Conclusion: Ixekizumab was efficacious in treating scalp psoriasis in patients with moderate-to-severe psoriasis, with most patients achieving complete or near-complete resolution of scalp psoriasis and maintaining this response over 60 weeks.

Keywords:

• Psoriasis
• scalp
• clinical trial
• UNCOVER
• ixekizumab
• interleukin-17A

Acknowledgements

The authors thank Bridget Charbonneau for her writing support.

Disclosure statement

K.R. holds stock in and/or has received compensation for serving on advisory boards, serving as a speaker, conducting research/clinical studies, and/or consulting for Abbvie, Amgen, Biogen, Boehringer Ingelheim, Celgene, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, Leo Pharmaceuticals, Eli Lilly and Co, Medac, Merck Sharp & Dohme Corp., Novartis, Pfizer, Regeneron, Takeda, UCB Pharma, and Xenoport. C.L. has received compensation for serving as a scientific consultant, clinical study investigator, and/or speaker for AbbVie, Amgen, Dermira, Janssen, Eli Lilly and Co, Leo, Sandoz, UCB, Pfizer, Actavis, Celgene, Coherus, Cermira, Galderma, Merck, Stiefel, Novartis, and Wyeth. M.L. is an employee of the Mount Sinai Medical Center, which receives research funds from AbGenomics, Amgen, Anacor, Boehringer Ingelheim, Celgene, Ferndale, Eli Lilly and Co, Janssen Biotech, Kadmon, Leo Pharmaceuticals, Medimmune, Novartis, Pfizer, Sun Pharmaceuticals, and Valeant. F.K. has received compensation for research and/or speaking and/or serving on and advisory board for Amgen, Galderma, Janssen, Abbvie, Celgene, Pfizer, Novartis, Astrazeneca, and Valeant. Y.O. has been a consultant, and/or scientific advisor, and/or investigator for Mitsubishi Tanabe Pharma Corporation, Maruho Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Eli Lilly and Company. R.R. has been a consultant, and/or scientific advisor, and/or investigator for AbbVie, Galderma, Janssen, Leo Pharma, Eli Lilly and Co, Novartis, Pfizer, and UCB. H.S. has received compensation for consultant, clinical investigator and/or speaker for AbbVie, Amgen, Dermira, Janssen, Eli Lilly, UCB, Pfizer, Celgene, Merck, Kadmon and UCB. O.G., E.B.D., and L.K. are employees of Eli Lilly and Co.

Funding

This study was sponsored by Eli Lilly and Company.