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CLINICAL REPORT
Long-term Impact of Ixekizumab on Psoriasis Itch Severity:
Results from a Phase III Clinical Trial and Long-term Extension
Alexandra B. KIMBALL 1 , Thomas LUGER 2 , Alice GOTTLIEB 3 , Luis PUIG 4 , Roland KAUFMANN 5 , Russel BURGE 6,7 , Chen-Yen
LIN 6 and Gil YOSIPOVITCH 8
Beth Israel Deaconess Hospital and Harvard Medical School, Boston, USA, 2 Department of Dermatology, University of Muenster, Muenster,
Germany, 3 Department of Dermatology, New York Medical College, Valhalla, USA, 4 Hospital de la Santa Creu i Sant Pau, Universitat Autònoma
de Barcelona, Barcelona, Spain, 5 Goethe University, Frankfurt, Germany, 6 Eli Lilly and Company, Indianapolis, 7 Winkle College of Pharmacy,
University of Cincinnati, Cincinnati, 8 Department of Dermatology, University of Miami Miller School Of Medicine, Miami, USA
1
Itching is a prevalent plaque psoriasis symptom. Ix-
ekizumab, an IL-17A antagonist, has demonstrated
rapid, significant improvements in itch severity over
12 weeks in Phase III psoriasis trials (UNCOVER-1,
UNCOVER-2). We assessed the long-term (through 60
weeks) effect of ixekizumab maintenance therapy (80-
mg ixekizumab every 4 weeks [IXEQ4W]) on itch seve-
rity, using the Itch Numeric Rating Scale, in psoriasis
patients who received ixekizumab, placebo, or etaner-
cept for 12 weeks in the Phase III UNCOVER-3 trial.
After 12 weeks, patients either continued or switched
to IXEQ4W. Mean improvements in itch severity achie-
ved with 12 weeks of ixekizumab (–4.7 to –5.1) were
maintained through 60 weeks with IXEQ4W (–4.9 to
–5.0). Patients who initially received placebo or eta-
nercept experienced rapid itch severity improvements
after switching to ixekizumab at Week 12 (Week 12,
placebo: –0.6; etanercept: –3.8; Week 60, placebo/IX-
EQ4W: –4.9; etanercept/IXEQ4W: –4.7). Ixekizumab
maintenance therapy sustained improvements in itch
severity through 60 weeks.
Key words: itch; itch NRS; ixekizumab; psoriasis; maintenance;
long-term outcomes.
Accepted Sep 19, 2017; Epub ahead of print Sep 20, 2017
Acta Derm Venereol 2018; 98: 98–102.
Corr: Alexa B. Kimball, MD, MPH, Beth Israel Deaconess Hospital and Har-
vard Medical School, 375 Longwood Ave, Boston, MA 02215, USA. E-mail:
[email protected]
P
soriasis is associated with symptoms such as itching
and skin pain, which can have a negative impact on
health-related quality of life (HRQoL) and functional sta-
tus (1–3). Itching (pruritus) is a prevalent plaque psoriasis
symptom, affecting more than 60% of patients. Many
patients complain that itch is their most troubling psoriasis
symptom (4). Itching is frequently associated with embar-
rassment and impairment of sleep, mood, concentration,
appetite, and sexual desire in psoriasis patients (5, 6).
Although itching is an important aspect of HRQoL
in psoriasis patients, the long-term management of itch
has not been well studied. Furthermore, instruments that
evaluate treatment efficacy in psoriasis clinical trials,
such as the Psoriasis Area and Severity Index (PASI) (7,
8), do not measure itch severity. Indeed, itch severity is
not directly correlated with PASI-measured disease ac-
doi: 10.2340/00015555-2801
Acta Derm Venereol 2018; 98: 98–102
tivity (9). Itch appears to be a domain independent from
disease severity and a mediator between improvements
in PASI and patient-reported HRQoL (10). To evaluate
psoriasis-related itch severity in a clinical setting, the
Itch Numeric Rating Scale (Itch NRS) was developed
and validated as a single-item, patient-reported outcome
(PRO) measure (11, 12).
Ixekizumab, a high-affinity monoclonal antibody that
selectively targets IL-17A (13), was recently evaluated
as a psoriasis therapy in Phase III clinical trials (UNCO-
VER-1, UNCOVER-2, and UNCOVER-3) and demon-
strated significantly greater and clinically meaningful
improvements in itch severity compared to placebo and
etanercept as early as Week 1; these improvements were
maintained through Week 12 (14–17).
This report describes the impact of long-term ixeki-
zumab maintenance therapy on itch severity through 60
weeks using data from the long-term extension (LTE)
period of the Phase III UNCOVER-3 trial.
METHODS
UNCOVER-3 (NCT01646177) was a Phase III randomized clini-
cal trial that evaluated ixekizumab versus placebo and etanercept
in moderate-to-severe psoriasis patients (14, 15). The trial was
conducted in accordance with the Declaration of Helsinki. All
study sites received institutional review board approval and all
patients provided written informed consent. At baseline (Week
0), patients were ≥ 18 years old with a confirmed chronic (≥ 6
months) plaque psoriasis diagnosis, ≥ 10% body surface area
involvement, a Static Physician’s Global Assessment (sPGA)
score ≥ 3, and a PASI score ≥ 12. Complete inclusion/exclusion
criteria and detailed methodology of the initial 12-week treatment
period has been described elsewhere (15). Bri