DISCREET highlights apremilast potential for genital psoriasis

Individuals with psoriasis creeping into their intimate areas may find relief from apremilast, as shown by the week-32 improvements in multiple disease parameters in the phase III DISCREET study.

An oral phosphodiesterase-4 inhibitor, apremilast has been given the FDA nod for the treatment of plaque psoriasis; however, its potential across the disease spectrum – including genital psoriasis – remains unclear.

“Genital psoriasis is common in patients with psoriasis and carries a significant burden,” said Dr Joseph Merola from the UT Southwestern Medical Center, Dallas, Texas, US, at EADV 2024. About two-thirds of patients with psoriasis experience genital psoriasis over the course of their disease, but it is often overlooked and undertreated.

The team evaluated 289 patients with moderate-to-severe (modified sPGA-G* [or genital PGA] score ≥3) genital psoriasis. They were randomized 1:1 to apremilast 30 mg BID or placebo for 16 weeks. After which, 229 patients (mean age 45.2 years, 70.3 percent men) entered an extension period wherein all received apremilast for an additional 16 weeks. Eighty-six percent had a modified genital PGA score of 3, while 88.6 percent had an overall sPGA score of 3. [EADV 2024, abstract 3339]

Skin, genital psoriasis symptoms

Week 16 saw better modified genital PGA response rates (score of 0/1 with a ≥2-point reduction from baseline) with apremilast vs placebo (38.7 percent vs 20.9 percent). The rate was generally maintained in the apremilast arm by week 32 (40.3 percent); in the placebo arm, the rate rose during the extension phase, reaching 51.8 percent at week 32. This means that up to half of treated patients achieved clear/almost clear genital skin with the transition from placebo to active treatment, Merola noted.

A similar pattern was seen in overall sPGA responses (score of 0/1 with a ≥2-point reduction from baseline) over time. In the apremilast arm, responses improved slightly from week 16 to 32 (from 22.7 percent to 30.3 percent). Among placebo recipients, there was a marked improvement between the two timepoints (from 8.2 percent to 33.6 percent).

Of note, 28.2 percent and 31.9 percent of participants in the respective apremilast and placebo arms achieved a modified genital PGA of 0 by week 32. The corresponding proportions of participants achieving an overall sPGA of 0 were 14.6 percent and 18.1 percent. These suggest that up to a third of patients achieved complete genital skin clearance, while nearly 20 percent achieved full skin clearance at week 32, noted Merola.

For genital itch response rates, the proportion of participants achieving GPI-NRS** responses in the apremilast arm was sustained between weeks 16 and 32 (from 44.6 percent to 46.5 percent). A slightly different pattern was seen in the placebo arm – the rate jumped from 18.9 percent at week 16 to 57.9 percent by week 24 but then dropped to 48.4 percent by week 32. Nonetheless, Merola noted that these rates translated to meaningful improvements in genital itch symptoms.

Other measures that improved with apremilast were BSA*** and GPSS^#. Among those who received apremilast across the entire study, mean percent change in BSA from baseline improved from –32.8 percent at week 16 to –45.9 percent at week 32. This trend was similarly seen for GPSS (from –44.6 percent to –51.4 percent). The improvements were greater in the placebo arm following the shift to apremilast (from –8 percent to –49.6 percent [BSA] and from –4 percent to –55.5 percent [GPSS]).

QoL, sexual health, safety

“Genital psoriasis is associated with painful and bothersome signs and symptoms, impairs quality of life (QoL), and negatively impacts sexual health,” said Merola. In DISCREET, QoL and sexual health improvements accompanied the skin improvements.

These were evidenced by the mean percent changes in DLQI^## in the apremilast arm from baseline to week 16 (–38.2 percent), further improving through week 32 (–48.6 percent). With placebo, the corresponding week-16 reduction was only 12.3 percent, but with the transition to apremilast, this dropped further to about 56 percent.

A similar pattern was seen for DLQI Question 9 (DLQI-Q9), a question asking about sexual difficulties arising from the skin issues. The mean percent change from baseline was nearly 60 percent by week 32 across both apremilast and placebo arms.

Moreover, about 30 percent of participants achieved a DLQI score of 0/1, while nearly 90 percent achieved a DLQI-Q9 response of 0/1 or ‘no impact’ by week 32.

Safety-wise, the week-32 outcomes mirrored those observed at week 16 and in other apremilast trials, Merola noted. Only one serious treatment-related treatment-emergent adverse event (TEAE) was reported with apremilast. The most common TEAEs were diarrhoea, nausea, and headache (25, 19, and 18 percent).

All parameters improved

“Apremilast is the first oral medication to be studied in patients with genital psoriasis using clinical measures specific for genital psoriasis,” said Merola.

Overall, DISCREET demonstrated that oral systemic therapy with apremilast rendered clinically meaningful improvements in disease severity, symptoms, and QoL at weeks 16 and 32, regardless of the treatment group during week 16, he noted. Safety outcomes also aligned with the drug’s known safety profile.

The results thus imply that apremilast may be an effective and safe treatment alternative for patients with genital psoriasis, the investigators said.