Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled, Phase IIIb clinical trial in patients with moderate-to-severe genital psoriasis

Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled, Phase IIIb clinical trial in patients with moderate-to-severe genital psoriasis

Presenters: Ryan C¹, Menter A², Guenther L³, Blauvelt A⁴, Bissonnette R⁵, Yang FE⁶, Potts Bleakman A⁶; Amato DA⁶

Affiliations: ¹Department of Dermatology, St. Vincent’s University Hospital, Dublin, Ireland; ²Menter Cosmetic Institute, Dallas, TX; ³Guenther Dermatology Research Centre, Ontario, Canada; ⁴Oregon Medical research Center, Portland, OR; ⁵Innovaderm Research, Quebec, Canada; ⁶Eli Lilly and Company, Indianapolis, IN

Background/Objectives: Genital psoriasis (gen-pso) is common among patients with plaque psoriasis. The condition negatively impacts quality of life and sexual health. Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of plaque psoriasis. This study’s objective was to evaluate the effect of IXE on gen-pso compared to placebo (PBO) during 12 weeks of treatment.

Methods: Patients with moderate-to-severe gen-pso (n=149) were randomized in a 1:1 ratio to receive either PBO (n=74) or 80mg IXE every two weeks (Q2W) following a starting dose of 160mg IXE (n=75). The primary endpoint was the percentage of patients achieving a 0 or 1 score on the 6-point static Physician’s Global Assessment of Genitalia (sPGA-G [0,1]) at Week 12. Major secondary endpoints included the percentage of patients achieving a 0 or 1 score on the 6-point overall sPGA (sPGA [0,1]), at least a three-point improvement on the 11-point Genital Itch (gen-itch) Numeric Rating Scale (NRS) for patients with a baseline score of at least 3, and a 0 or 1 score for the 5-point Sexual Frequency Questionnaire Item 2 (SFQ-item 2 [0,1]) (indicating that the frequency of sexual activity is never or rarely limited by gen-pso) for patients with a baseline SFQ-Item 2 score of at least 2. Treatment comparisons were made using logistic regression analysis with non-responder imputation for missing data. Clinicaltrials.gov ID: NCT02718898.

Results: IXE Q2W treatment led to significantly greater sPGA-G (0, 1) response rates (73.3%) than PBO (8.1%) at Week 12 (p<0.001). Similarly, overall sPGA (0, 1) response rates were significantly greater with IXE Q2W (73.3%) compared to PBO (2.7%, p<0.001). IXE Q2W led to significantly greater gen-itch NRS response rate (59.7%) at Week 12 versus PBO (8.3%, p<0.001). Significantly more patients achieved SFQ-item 2 (0, 1) with IXE Q2W (78.4%) than PBO (21.4%, p<0.001). Significant improvements in response rates were observed by Week 1 for sPGA-G (0,1) (p<0.01), overall sPGA (0,1) (p<0.001), and SFQ-item 2 (0, 1) (p<0.05), and by Week 2 for gen-itch NRS (p<0.001). Frequencies of treatment-emergent adverse events (TEAEs) through Week 12 were 56.0 percent and 44.6 percent in IXE Q2W and PBO groups, respectively; the majority were mild or moderate in severity. Common TEAEs in the IXE Q2W population included upper respiratory tract infections, injection site reactions, headache, oropharyngeal pain, and pruritus. No cases of candidiasis were reported, no deaths occurred, and only one (1.4%) serious adverse event was reported in a patient receiving PBO.

Conclusion: IXE Q2W was superior to PBO for the primary and all major secondary endpoints as early as Week 1 and safety outcomes were comparable to previously reported IXE Phase III trials. These results indicate that IXE is an efficacious treatment of moderate-to-severe gen-pso and minimizes how often gen-pso limits the frequency of sexual activity.