Patients with palmoplantar pustulosis (PPP) treated with apremilast show improvements at week 16, with continued treatment resulting in maintained or further improvement at week 52, according to a study presented at AAD 2025. No new safety concerns have been observed.

“These included improvements in severity and symptoms (pruritus and pain/discomfort) and patient-reported quality of life,” said lead author Dr Yukari Okubo from Tokyo Medical University, Tokyo, Japan.

A total of 176 patients with PPP (80 percent women) were randomly allocated in a 1:1 ratio to receive either apremilast (n=88) or placebo (n=88) between March 2022 and April 2023. Of these, 164 (93.2 percent) completed treatment until week 52 (apremilast group: n=84, 95.5 percent; placebo group: n=80, 90.9 percent). [AAD 2025, abstract 59589]

A significantly greater proportion of patients treated with apremilast, compared with placebo, achieved ≥50-percent improvement in PPP Area and Severity Index (PPPASI; 68 percent vs 35 percent; treatment difference, 32.6 percent, 95 percent confidence interval, 18.7?46.5; p<0.0001). [https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5070298]

Improvements seen at week 16 either persisted or further grew at week 52 in patients who continued treatment with apremilast: ≥50-percent improvement in PPPASI total score (response rate [RR], 79.8 percent), 70-percent improvement in PPPASI (RR, 47.6 percent), and 90-percent improvement in PPPASI (RR, 20.2 percent).

Other developments included changes from baseline in PPPASI total score (?14.7), Palmoplantar Pustulosis Severity Index (PPSI) total score (?4.6), pruritus visual analogue scale (VAS; ?19.1), pain/discomfort VAS (?18.8), and Dermatology Life Quality Index (DLQI; ?2.4).

Transition to apremilast

Patients who switched from placebo to apremilast also demonstrated similar improvements from week 16 to week 52. In addition, treatment-emergent adverse events (TEAEs) reported were consistent with the known safety profile of apremilast.

“Transitioned patients achieved response rates similar to the apremilast group by week 20 for PPPASI and PPSI and by week 24 for patient-reported outcomes,” Okubo said.

The most common TEAE was diarrhoea (19 percent in the apremilast group vs 3 percent in the placebo group), followed by soft faeces (17 percent vs 1 percent), headache (11 percent vs 2 percent), and nausea (11 percent vs 1 percent). No incidence of depression or fatal adverse events were reported. [https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5070298]

This phase III, randomized, placebo-controlled study enrolled adults with PPPASI total score ≥12, PPPASI pustules/vesicles severity score ≥2, and inadequate response to topical medications. Okubo and colleagues randomly assigned eligible participants to apremilast 30 mg twice daily or placebo for 16 weeks, after which all patients received apremilast through week 52.

The following endpoints were then assessed at week 52: ≥50-percent, 75-percent, and 90-percent improvement in PPPASI total score; changes from baseline in PPPASI total score, PPSI total score, patient’s VAS for pruritus and pain/discomfort, DLQI, and TEAEs.

PPP is a “difficult-to-treat condition” in patients with chronic dermatitis, characterized by itching and pain, and has limited treatment options, according to the researchers.

“Apremilast, an oral phosphodiesterase 4 inhibitor approved for the treatment of plaque psoriasis, psoriatic arthritis, and oral ulcers associated with Beh?et’s disease, has demonstrated significant efficacy in Japanese patients with moderate to severe PPP,” Okubo said.