Efficacy of ixekizumab compared to etanercept and placebo in patients with moderate-to-severe plaque psoriasis and non-pustular palmoplantar involvement: results from three phase 3 trials (UNCOVER-1, UNCOVER-2 and UNCOVER-3).
BACKGROUND
Palmoplantar psoriasis has significant physical and emotional impact on patients and can be difficult to treat.


OBJECTIVE
To evaluate the efficacy of ixekizumab in the treatment of patients with moderate-to-severe plaque psoriasis and moderate-to-severe non-pustular palmoplantar involvement.


METHODS
In three phase 3, double-blind, placebo-controlled trials, patients with moderate-to-severe non-pustular plaque psoriasis [UNCOVER-1 (N = 1296), UNCOVER-2 (N = 1224), UNCOVER-3 (N = 1346)] were randomized to subcutaneous 80 mg ixekizumab every 2 or 4 weeks (Q2W, Q4W), after a 160-mg starting dose, or placebo through week 12. Additional UNCOVER-2 and UNCOVER-3 cohorts were randomized to 50 mg etanercept biweekly. Patients entering the open-label long-term extension (UNCOVER-3) received ixekizumab Q4W weeks 12-60. Moderate-to-severe palmoplantar involvement was defined as Palmoplantar Psoriasis Area and Severity Index (PPASI) ≥8.


RESULTS
Twenty-eight percent of UNCOVER-1, UNCOVER-2 and UNCOVER-3 patients had baseline palmoplantar involvement (PPASI ≥0, n = 1092) and 9.1% (n = 350) had moderate-to-severe involvement, with mean baseline PPASI ~20, PASI ~24, and most (>60%) had static Physician's Global Assessment ≥4. Higher percentages of patients treated with ixekizumab vs. placebo or etanercept achieved PPASI 50 (approximately 80% vs. 32.9%, 67.8%; ixekizumab, placebo, etanercept, respectively) and PPASI 75 (approximately 70% vs. 18.8%, 44.1%; ixekizumab, placebo, etanercept, respectively) at week 12 (all P < 0.05). PPASI 100 was achieved by higher percentages of ixekizumab-treated patients vs. placebo (approximately 50% vs. 8.2%, P < 0.001) and ixekizumab Q2W-treated patients vs. etanercept (51.8% vs. 32.2%, P < 0.05). Outcomes were maintained or improved in patients continuing on ixekizumab Q4W through week 60. Differences between ixekizumab and placebo or etanercept were statistically significant as early as week 1.


CONCLUSIONS
In a subpopulation analysis of patients from phase 3 trials with moderate-to-severe non-pustular palmoplantar involvement and moderate-to-severe plaque psoriasis, ixekizumab treatment resulted in greater and more rapid improvements than placebo and etanercept at week 12; improvements were sustained with continued treatment.
Baylor University Medical Center, Dallas, TX, USA.
A
A
Menter
Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health, Science Centre, University of Manchester, Manchester, UK.
R B
RB
Warren
Dalhousie University, Halifax, NS, Canada.
R G
RG
Langley
Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
J F
JF
Merola
Eli Lilly and Company, Indianapolis, IN, USA.
L N
LN
Kerr
Eli Lilly and Company, Indianapolis, IN, USA.
E B
EB
Dennehy
Eli Lilly and Company, Indianapolis, IN, USA.
D
D
Shrom
Eli Lilly and Company, Indianapolis, IN, USA.
D
D
Amato
Department of Dermatology, Tokyo Medical University, Tokyo, Japan.
Y
Y
Okubo
Dermatologikum Hamburg and SCIderm GmbH, Hamburg, Germany.
K
K
Reich
D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003879:Dermatologic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D000068800:Etanercept / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D003879:Dermatologic Agents; D010919:Placebos; C549079:ixekizumab; D000068800:Etanercept