1. Efficacy and Safety of Ixekizumab in a Randomized, Double-Blinded, Placebo-Controlled Phase 3b Study of Patients with Moderate-to-Severe Genital Psoriasis
C Ryan,1 A Menter,2 L Guenther,3 A Blauvelt,4 R Bissonnette,5 K Meeuwis,6 J Sullivan,7 JC Cather,8 G Yosipovitch,9 AB Gottlieb,10 JF Merola,11 K Callis Duffin,12 S Fretzin,13 OO Osuntokun,14 R Burge,14 AN Naegeli,14 FE Yang,14 C-Y Lin,14 K Todd,14 A Potts Bleakman,14 on behalf of the IXORA-Q Study Group
1Department of Dermatology, Blackrock Clinic, Dublin, Ireland
2Department of Dermatology, Baylor University Medical Center, Dallas, TX, USA
3Guenther Dermatology Research Centre, London, ON, Canada
4Oregon Medical Research Center, Portland, OR, USA
5Innovaderm Research, Montreal, QC, Canada
6Department of Dermatology, Radboud University Medical Center, Nijmegen, The Netherlands
7Kingsway Dermatology, Miranda, NSW, Australia
8Modern Research Associates, Dallas, TX, USA
9Department of Dermatology and Itch Center, University of Miami School of Medicine, Miami, FL, USA
10Department of Dermatology, New York Medical College at Metropolitan Hospital, New York, NY, USA
11Department of Dermatology and Medicine, Division of Rheumatology, Harvard Medical School Brigham and Women’s Hospital, Boston, MA, USA
12Department of Dermatology, University of Utah School of Medicine, Salt Lake City, UT, USA
13Dawes Fretzin Dermatology Group, Indianapolis, IN, USA
14Eli Lilly and Company, Indianapolis, IN, USA
British Journal of Dermatology. DOI: /bjd.16736

2. Introduction What’s already known?
Genital psoriasis is a common and burdensome form of plaque psoriasis but there are few controlled studies of effective therapies.

3. Objective
To determine the efficacy of ixekizumab versus placebo in patients with moderate-to-severe genital psoriasis with BSA≥1%.

4. Methods Study design: Statistical analysis: Patients randomized 1:1
Placebo (PBO): every 2 weeks through week 12
Ixekizumab (IXE): 80 mg IXE every 2 weeks through week 12 (160-mg starting dose at week 0)
Statistical analysis:
Efficacy: all randomized patients (intention-to-treat analysis)
Categorical variables: logistic regression with non-responder imputation
Continuous variables: mixed-effects model for repeated measures
Safety: randomized patients who received ≥1 dose of investigational product

5. Methods Primary endpoint: Major secondary endpoints:
sPGA-G 0/1: proportion of patients at week 12 achieving clear (0) or minimal (1) on the static Physician’s Global Assessment of Genitalia (sPGA)
Major secondary endpoints:
Overall sPGA 0/1: proportion of patients at week 12 achieving clear (0) or minimal (1) on the overall sPGA
Genital itch NRS ≥3: proportion of patients at week 12 achieving a ≥3-point improvement from baseline on the genital itch numeric rating scale (among patients with a baseline score ≥3)
Cont.

6. Methods
GenPs-SFQ item 2 0/1: proportion of patients at week 12 achieving a Sexual Frequency Questionnaire (SFQ) item 2 score of 0 or 1 (among patients with a baseline score ≥2)
GenPs-SFQ item 2 0/1 indicates sexual activity was never (0) or rarely (1) limited by genital psoriasis

7. Methods Patients: Adults with chronic plaque psoriasis for ≥6 months
Had plaque psoriasis in a non-genital area
Had an sPGA-G ≥3, Overall sPGA ≥3, and Body Surface Area (BSA) involvement ≥1%
Had previously failed to respond to, or intolerant of, ≥1 topical therapy for genital psoriasis

8. Methods Did not have forms of psoriasis other than plaque psoriasis
Had no pustules or vesicles in the genital area
Never received previous treatment with IL-17 antagonists
No recent history of suicide attempt or score of 3 on item 12 (thoughts of death or suicide) on the Quick Inventory of Depressive Symptomatology Self Report (16 items)

9. Baseline Characteristics and Safety Outcomes
Baseline demographics and disease characteristics
Placebo
(N=74)
Ixekizumab
(N=75)
Age, years
44.4 (12.6)
43.1 (13.0)
Male, n (%)
57 (77.0)
56 (74.7)
Caucasian, n (%)
64 (86.5)
67 (89.3)
Weight, kg
95.1 (26.3)
91.9 (23.1)
sPGA-G
3.5 (0.5)
3.4 (0.6)
Overall sPGA
3.5 (0.6)
Genital itch NRS score
6.0 (2.4)
5.9 (2.4)
GenPs-SFQ Item 2 score
2.0 (1.6)
1.8 (1.7)
% BSA
16.8 (15.7)
14.2 (12.6)
1 to <10%, n (%)
28 (37.8)
31 (41.3)
≥10%, n (%)
46 (62.2)
44 (58.7)
Unless otherwise indicated, all values are presented as mean (SD)
Adverse events during the blinded treatment period (Week 0-12) of IXORA-Q
Placebo
N=74
Ixekizumab
N=75
Treatment emergent adverse events
33 (44.6)
42 (56.0)
Mild
15 (20.3)
23 (30.7)
Moderate
18 (24.0)
Severe
3 (4.1)
1 (1.3)
Serious adverse event
1 (1.4)
Discontinuation due to adverse event
5 (6.8)
Death
Values are presented as n (%) of patients

10. Improvement of Genital Psoriasis During 12 Weeks of Treatment with Ixekizumab
73%***
56%*** 8% 5%
* = p<0.05, ** = p<0.005, *** = p<0.001

11. Overall sPGA, Genital Itch NRS, and GenPs-SFQ Item 2 Response During 12 Weeks of Treatment with Ixekizumab
73%***
40%***
78%*** 3% 0%
21%
60%*** 8%
* = p<0.05, ** = p<0.005, *** = p<0.001

12. Discussion
Ixekizumab was superior to placebo for the treatment of moderate-to-severe genital psoriasis at week 12.
Response was rapid, with significant improvements observed as early as week 1.
Improvement in genital psoriasis was consistent in patients with both lower (1 to <10%) and higher (≥10%) BSA involvement.
Safety profile was consistent with other studies of ixekizumab in overall psoriasis and psoriatic arthritis.

13. Discussion Strengths: Limitations:
The only phase 3, randomized, placebo-controlled, double-blind clinical trial to evaluate the efficacy of any therapy for the treatment of genital psoriasis.
The study population was globally diverse (34 sites in 7 countries).
Included patients with both lower and higher BSA involvement.
Limitations:
No active comparator as there are no well-established treatments for genital psoriasis.
Predominantly Caucasian and male study population.
Short duration of treatment (study is ongoing to collect longer term results).

14. Discussion
Although a common and burdensome form of psoriasis, only a few open-label studies have evaluated the efficacy of treatments for genital psoriasis.
Ixekizumab provided rapid and significant improvement in genital psoriasis compared to placebo, with consistent improvement across BSA subgroups.

15. Conclusions What does this study add?
Ixekizumab significantly improved the severity of genital psoriasis and associated disease characteristics.
Ixekizumab may be appropriate for moderate-to-severe genital psoriasis treatment, even in patients with limited body surface involvement.

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