New Phase 3 DISCREET Data Supports Long-Term Use of Apremilast for Genital Psoriasis

Genital psoriasis is a burdensome and frequently underreported manifestation of psoriasis associated with pain, pruritus, sexual dysfunction, and substantial quality-of-life impairment. New phase 3 data has demonstrated the 32-week efficacy and safety data for apremilast in adults with moderate to severe disease.¹

Methods & Materials

DISCREET is the first randomized, double-blind, placebo-controlled study specifically designed to evaluate an oral systemic therapy in genital psoriasis using genital-specific clinical endpoints. In this multicenter trial (NCT03777436), 289 patients were randomized 1:1 to apremilast 30 mg twice daily or placebo for 16 weeks, followed by a 16-week extension phase in which all patients received apremilast.

Eligible patients had moderate to severe genital psoriasis, defined by a modified static Physician’s Global Assessment of Genitalia (genital PGA) score ≥3, and disease inadequately controlled by or intolerant to topical therapy. Concomitant systemic or biologic therapies were not permitted. Of the randomized population, 229 patients entered the extension phase and 201 completed 32 weeks. The baseline mean Dermatology Life Quality Index score (DLQI) was 12.9.

Primary Results

At week 16, previously reported primary results demonstrated superiority of apremilast over placebo for modified genital PGA response (clear or almost clear with ≥2-point reduction). Over 32 weeks, these responses were maintained or improved. At week 32, 51.8% of patients who switched from placebo to apremilast at week 16 and 40.3% of those treated with apremilast continuously achieved a modified genital PGA response. Overall static PGA responses at week 32 were 33.6% and 30.3%, respectively. Nearly 30% of patients achieved complete genital skin clearance by week 32.

Improvements in overall skin involvement were also observed. Mean change in body surface area (BSA) at week 32 was −4.4% in the placebo/apremilast group and −5.3% in the apremilast/apremilast group, demonstrating sustained reductions in cutaneous disease activity. Patient-reported outcomes also paralleled improvements assessed by physicians. Among patients with baseline genital itch scores ≥4, approximately 47% in both treatment groups achieved a ≥4-point improvement in Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) by the end of the trial. Mean reductions in Genital Psoriasis Symptoms Scale (GPSS) total scores were substantial (−25.7 and −25.0 points in the placebo/apremilast and apremilast/apremilast groups, respectively), reflecting improvements across itch, pain, burning, redness, scaling, and cracking.

Quality of life measures also improved meaningfully. At the conclusion of the study, the mean change from baseline in DLQI was −7.4 in the placebo/apremilast group and −6.1 in the continuous apremilast group. More than one-quarter of patients achieved a DLQI score of 0 or 1, indicating no or minimal impact of disease on life. Sexual health, assessed by DLQI Question 9 (DLQI-Q9), showed marked improvement: mean change from baseline was −0.9 and −0.7, and approximately half of evaluable patients achieved a DLQI-Q9 score of 0 at week 32. Post hoc analyses demonstrated the strongest agreement between reductions in genital itch (GPI-NRS response) and improvements in overall and sexual quality of life.

Further Analysis

Subgroup analyses by sex showed benefit in both men and women, although women demonstrated numerically greater improvements in several endpoints, including genital PGA, itch response, DLQI, and sexual quality of life measures. Given that women often report greater symptom burden and sexual distress related to genital psoriasis, these findings are clinically notable, though the study population was predominantly male (70%).²

Safety findings over 32 weeks were consistent with the established profile of apremilast. Among 252 patients exposed to apremilast (107 patient-years), 69% reported at least 1 treatment-emergent adverse event. The most common events were diarrhea (25.4%), nausea (19.4%), headache (17.9%), and nasopharyngitis (8.3%), generally occurring early and aligning with prior psoriasis studies. Serious adverse effects were infrequent (2.0%), and 6.3% discontinued treatment due to adverse events, most commonly gastrointestinal symptoms or depression. No new safety signals emerged with extended exposure.

Conclusion

Limitations may include the absence of a placebo comparator beyond week 16, limited sexual function assessment beyond DLQI-Q9, and relatively short 32-week follow-up. Nevertheless, for patients with moderate to severe genital psoriasis who are inadequately controlled on topical therapy or prefer an oral systemic option, apremilast represents a clinically meaningful treatment alternative, according to this new data.

References

1. Merola JF, Guenther L, Lynde C, 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. 2026;40(2):274-284. doi:10.1111/jdv.70110

2. Meeuwis KA, van de Kerkhof PC, Massuger LF, de Hullu JA, van Rossum MM. Patients' experience of psoriasis in the genital area. Dermatology. 2012;224(3):271-276. doi:10.1159/000338858