Results from the 32‐week, phase 3 DISCREET study of apremilast in patients with moderate to severe genital psoriasis

TL;DR

Apremilast, an oral medication, effectively and safely treats genital psoriasis over 32 weeks, improving symptoms and quality of life.

Contribution

Demonstrates long-term efficacy and safety of apremilast for genital psoriasis beyond initial 16-week results.

Findings

At 32 weeks, 51.8% of patients who switched from placebo to apremilast achieved improved genital psoriasis scores.

Apremilast improved symptoms like itching and quality of life, with benefits more pronounced in women.

Safety profile remained consistent with prior studies, with no new safety concerns identified.

Abstract

Genital psoriasis is highly prevalent among patients with psoriasis, is often stigmatized, causes pain and discomfort and negatively impacts quality of life. Apremilast is an oral phosphodiesterase 4 inhibitor approved for treating psoriasis and has demonstrated safety and efficacy in treating genital psoriasis, as seen in the primary 16‐week DISCREET results.

To assess the efficacy and safety of apremilast 30 mg twice daily in patients with moderate to severe genital psoriasis over the 32‐week study duration.

DISCREET was a phase 3, multicentre, randomized, double‐blind trial that evaluated apremilast 30 mg twice daily versus placebo in a 16‐week placebo‐controlled phase (randomization 1:1) followed by a 16‐week apremilast extension phase. Patients had moderate to severe genital psoriasis, defined as a modified static Physician's Global Assessment of Genitalia (genital PGA) score of ≥3. They also either had disease inadequately controlled by or were intolerant to topical therapy. We report the results through Week 32.

Of 289 patients randomized, 229 continued to the apremilast extension phase (Weeks 16–32): 110 in the placebo/apremilast group and 119 in the apremilast/apremilast group. At 32 weeks, 51.8% (95% CI: 42.6, 60.9) of patients in the placebo/apremilast group and 40.3% (95% CI: 32.0, 49.3) of patients in the apremilast/apremilast group had achieved a modified genital PGA response (score of 0/1 with ≥2‐point reduction from baseline). At Week 32, similar improvements in skin, genital signs and symptoms and quality of life were observed in patients who started apremilast at Week 16 or at randomization. Frequently reported treatment‐emergent adverse events during all‐apremilast exposure were diarrhoea (25.4%), nausea (19.4%) and headache (17.9%).

Apremilast is an effective oral systemic therapy in patients with moderate to severe genital psoriasis and has shown consistent clinical efficacy, lessening of symptoms and quality‐of‐life benefit in DISCREET.

NCT03777436.

Patients with psoriasis often have symptoms in the genital area. Genital psoriasis can cause uncomfortable symptoms such as itching, burning, flaking, and pain, as well as embarrassment and negative effects on sexual and mental health. Few clinical studies have focused on treatments specifically for genital psoriasis. Steroid creams are commonly prescribed, however some patients dislike this treatment due to side effects, inconvenience, messiness, and lack of effectiveness.

In the multinational DISCREET study, we examined how effective and safe ‘apremilast’ (an oral medication) was in treating moderate to severe genital psoriasis. We previously reported that apremilast was safe and effective over 16 weeks compared to ‘placebo’ (a dummy drug containing no active ingredients). Here we report the long‐term results over 32 weeks. In total, 289 patients received either apremilast or placebo for 16 weeks, after which all patients received apremilast until week 32.

At 32 weeks, nearly half (46%) of all patients achieved clear or almost clear genital skin; patients who received apremilast throughout the entire 32‐week study and patients who switched from placebo to apremilast at 16 weeks experienced similar effectiveness. Patients also had improvements in genital itch and other symptoms, as well as in general and sexual well‐being. Both women and men benefited from apremilast, with the benefit more pronounced in women. No new safety concerns were identified compared to previous studies.

In conclusion, these findings indicate that apremilast is an effective and safe oral medication for patients with moderate to severe genital psoriasis.

During the extension phase of the 32‐week DISCREET trial, apremilast treatment in patients with moderate to severe genital psoriasis led to clinically meaningful improvements in disease severity (modified genital PGA, overall sPGA, BSA), symptoms (genital itch, GPSS), and quality of life (DLQI, DLQI‐Q9), with safety outcomes consistent with prior studies.

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