Long-Term Efficacy and Safety of Apremilast in Moderate to Severe Genital Psoriasis: The 32-Week DISCREET Extension Data

Highlights

Sustained Clinical Response

At week 32, over half of the patients who switched from placebo to apremilast at week 16 achieved a modified genital Physician’s Global Assessment (sPGA-G) response, matching the efficacy seen in the continuous treatment group.

Significant Quality-of-Life Improvements

Beyond clinical skin clearance, the study reported substantial improvements in patient-reported outcomes, including reduced genital pain, itch, and the psychological burden associated with the disease.

Manageable Safety Profile

Adverse events remained consistent with the known safety profile of apremilast, with gastrointestinal symptoms being the most frequent but generally transient in nature.

Background: The Unmet Need in Genital Psoriasis

Genital psoriasis is a frequent and distressing manifestation of psoriasis vulgaris, affecting up to 63% of patients at some point during their disease course. Despite its prevalence, it remains one of the most undertreated and stigmatized areas of dermatology. The clinical presentation—characterized by bright red, thin plaques with minimal scaling—often causes intense pruritus, burning, and pain. These symptoms are frequently exacerbated by friction and perspiration, leading to a profound negative impact on sexual health, interpersonal relationships, and overall quality of life.

Historically, the management of genital psoriasis has been restricted to topical therapies, including low-to-mid-potency corticosteroids and calcineurin inhibitors. However, the sensitive nature of the genital skin limits the long-term use of steroids due to risks of skin atrophy, striae, and secondary infections. Furthermore, many patients find topical applications messy or inconvenient, leading to poor adherence. Systemic therapies and biologics have shown efficacy, but many are not specifically indicated or studied for the genital subtype. Apremilast, an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4), offers a systemic approach without the requirement for laboratory monitoring, making it an attractive option for this specific patient population.

Study Design: The DISCREET Protocol

DISCREET was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of apremilast 30 mg twice daily. The study enrolled 289 patients with moderate to severe genital psoriasis, defined by a modified static Physician’s Global Assessment of Genitalia (genital PGA) score of 3 or higher. Inclusion criteria also required patients to have had an inadequate response to or intolerance of topical therapies.

The trial was divided into two distinct phases. The first 16 weeks comprised a placebo-controlled phase where patients were randomized 1:1 to receive either apremilast or a matching placebo. Following this, all patients entered a 16-week open-label extension phase (Weeks 16 to 32), during which those originally in the placebo group transitioned to apremilast (placebo/apremilast group), while those already on the drug continued their regimen (apremilast/apremilast group). The primary endpoint was the proportion of patients achieving a modified genital PGA response (defined as a score of 0 or 1 with at least a 2-point reduction from baseline) at Week 16, which has been previously reported. The current analysis focuses on the durability of response and safety through the full 32-week period.

Key Findings: 32-Week Results

Of the initial 289 randomized patients, 229 successfully transitioned into the extension phase. The longitudinal data suggests that the clinical benefits of apremilast are not only sustained but may continue to evolve over time.

Clinical Efficacy and Skin Clearance

At the 32-week mark, 51.8% (95% CI: 42.6, 60.9) of patients in the placebo/apremilast group achieved the modified genital PGA response. In the group that received apremilast from the outset (apremilast/apremilast), 40.3% (95% CI: 32.0, 49.3) maintained or achieved this response. The observation that the switch group showed a high response rate suggests a rapid therapeutic onset once the active drug is introduced. Furthermore, improvements in the Body Surface Area (BSA) affected by psoriasis and the overall static Physician’s Global Assessment (sPGA) mirrored the improvements seen in the genital-specific scores.

Symptom Relief and Quality of Life

Genital psoriasis is uniquely burdensome due to its location. The DISCREET study utilized several secondary endpoints to capture this, including the Genital Psoriasis Symptoms Scale (GPSS). Patients in both groups reported significant reductions in itch, burning, and pain. By week 32, quality-of-life scores, measured by the Dermatology Life Quality Index (DLQI), showed that a substantial portion of patients no longer felt their skin condition had a major impact on their lives. This is particularly relevant for genital psoriasis, where the psychological relief of clearance often outweighs the clinical measurement of plaque thickness.

Safety and Tolerability Profile

Throughout the 32-week exposure, the safety profile of apremilast remained consistent with previous phase 3 trials in plaque psoriasis and psoriatic arthritis. The most frequently reported treatment-emergent adverse events (TEAEs) were:

1. Diarrhea (25.4%)
2. Nausea (19.4%)
3. Headache (17.9%)

Most of these events were mild to moderate in severity and typically occurred within the first two weeks of treatment initiation. In most clinical cases, these symptoms resolve within a few weeks without the need for discontinuation. No new safety signals were identified during the extension phase, and the incidence of serious adverse events remained low. Weight loss, a known side effect of PDE4 inhibition, was monitored and found to be consistent with previous observations, usually not requiring intervention.

Expert Commentary: Clinical Implications

The results of the DISCREET trial represent a significant step forward in the management of genital psoriasis. From a mechanistic perspective, apremilast works by increasing intracellular levels of cyclic adenosine monophosphate (cAMP), which in turn modulates the expression of several pro-inflammatory and anti-inflammatory cytokines. This systemic modulation is particularly effective for genital psoriasis, where the underlying inflammation is often driven by the same IL-23/IL-17 axis seen in general plaque psoriasis, but exacerbated by local skin sensitivity.

Clinicians should note the importance of the 32-week data in confirming that the initial 16-week results were not transient. For many patients, the genital area is the most distressing part of their disease. The availability of an oral agent that does not require regular blood monitoring—unlike methotrexate or cyclosporine—provides a middle ground between topical failure and the transition to injectable biologics. While biologics remain highly effective, some patients prefer oral administration or may have contraindications to certain biologic classes.

A limitation of the study, common to extension phases, is the potential for attrition bias, as patients who did not respond well in the first 16 weeks might have been more likely to drop out. However, the high completion rate in DISCREET (229 out of 289) lends confidence to the generalizability of these findings for moderate to severe cases.

Conclusion

In the 32-week DISCREET trial, apremilast demonstrated durable efficacy in treating moderate to severe genital psoriasis. The data confirms that apremilast not only clears genital lesions but also significantly reduces the associated symptoms of pain and itch, leading to a meaningful improvement in patient quality of life. With a well-characterized and manageable safety profile, apremilast stands as a robust oral systemic option for patients who have failed topical therapy, addressing a critical gap in the dermatological treatment armamentarium.

Funding and Clinical Trial Information

This study was funded by Amgen Inc. The trial is registered at ClinicalTrials.gov with the identifier NCT03777436.

References

Merola JF, Guenther L, Lynde C, Papp KA, Parish LC, Yamauchi P, Cheng S, Amouzadeh H, Deignan C, Jardon S, Chen M, Pinter A. 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 Feb;40(2):274-284. doi: 10.1111/jdv.70110. Epub 2025 Dec 10. PMID: 41369155; PMCID: PMC12843872.