Apremilast Effective Treatment for Moderate to Severe Genital Psoriasis at 32 Weeks

Apremilast is effective as an oral systemic therapy for moderate to severe genital psoriasis, new data suggest, with consistent clinical efficacy, symptoms improvements, and quality-of-life benefits.1

These findings from the phase 3 DISCREET study (NCT03777436) followed 32 weeks of analysis of this drug’s impact on genital psoriasis. Apremilast is an oral phosphodiesterase-4 (PDE4)-inhibitor approved for patients living with psoriasis. The medication previously demonstrated safety and efficacy in treating genital psoriasis following the 16-week results of DISCREET.2

This new 32-week analysis, authored by investigators such as Joseph F. Merola, MD, MMSc, of UT Southwestern Medical Center, explored the twice-daily use of apremilast in the same patient group following the primary findings released at the 16-week mark.

“Product labelling in the United States has been revised to include these data supporting the efficacy of apremilast in genital psoriasis,” Merola et al wrote.1 “We report 32-week safety and efficacy results as well as post-hoc analyses of efficacy results.”

Trial Design and Findings on Apremilast

In their analysis, Merola and coauthors described the design of the DISCREET trial as randomized, double-blind, and placebo-controlled. The investigators' research was conducted across multiple centers located in Canada, Belgium, France, Italy, the US, and Germany. While details of DISCREET's design and methodology were previously highlighted, the team noted participants were assigned in a 1:1 ratio to be treated either with apremilast or placebo through a centralized Interactive Response Technology system via permuted block randomization.

Adults with moderate to severe genital psoriasis, as indicated by a baseline modified static Physician’s Global Assessment of Genitalia (genital PGA or sPGA-G) score of 3 or higher, were deemed as eligible to take part in the trial. All of those involved as participants had either insufficient response to or intolerance of topical drugs. Additionally, these individuals would also have had moderate to severe chronic plaque psoriasis for at least half a year, defined as an overall static Physician’s Global Assessment (sPGA) score of 3 at least, and non-genital plaque psoriasis involving at least 1% of patients' body surface area (BSA).

In terms of treatment Merola et al administered apremilast 30 mg, taken orally, on a twice-daily basis or provided participants with a matched placebo for 16 weeks during the placebo-controlled phase of DISCREET. This was then followed by a 16-week extension phase, during which the investigators provided all subjects with apremilast. Individuals who had been on placebo switched to active therapy from Weeks 16 - 32 (placebo/apremilast cohort). At the same time, individuals originally assigned to the apremilast cohort continued treatment for the full 32 weeks (apremilast/apremilast group).

At screening, at baseline, and at the 2, 4, 8, 12, 16, 20, 24, and 32-week marks, study visits took place. Merola and colleagues' follow-up interaction took place 4 weeks following the last apremilast dose. There were 289 patients who were randomized, with 229 entering the study's apremilast extension period. Among these subjects, 110 were transitioned by Merola and coauthors from placebo to apremilast at the 16-week mark. 119 remained on continuous apremilast throughout.

By Week 32, the investigative team found attainment of a modified genital PGA response, defined as a score of 0 or 1 with a reduction of at least 2 points from baseline, was seen among 51.8% of those included in the placebo/apremilast group (95% CI: 42.6–60.9).1 It was also seen among 40.3% of the apremilast/apremilast group (95% CI: 32.0–49.3).

By the conclusion of the study's 32-week period, the team identified improvements in overall skin disease, genital psoriasis signs and symptoms, and quality-of-life measures. They also found these results to be comparable between subjects who initiated apremilast at randomization and those who began treatment at the 16-week mark.1

Additionally, the Merola et al's safety findings revealed the most commonly reported treatment-emergent adverse events during apremilast exposure to be instances of diarrhea (25.4%), nausea (19.4%), and headaches (17.9%).1

“Based on the consistent clinical efficacy, improvements in symptoms and QoL benefit seen in DISCREET, apremilast appears to be an effective oral therapy in patients with moderate to severe genital psoriasis,” the investigators wrote.1

References

1. Merola JF, Guenther L, Yamauchi P, et al. Results from the 32-week, phase 3 DISCREET study of apremilast in patients with moderate to severe genital psoriasis. J Eur Acad Dermatol Venereol. 2025; 00: 1–11. https://doi.org/10.1111/jdv.70110.

2. Merola JF, Parish LC, Papp KA, et al. Efficacy and safety of apremilast in patients with moderate-to-severe genital psoriasis: Results from DISCREET, a phase 3 randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2024 Mar;90(3):485-493. doi: 10.1016/j.jaad.2023.10.020. Epub 2023 Oct 16. PMID: 37852306.