Efficacy and Safety of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: Results from a Phase 2, Randomized, Placebo-Controlled Study

Abstract

Background Palmoplantar pustulosis (PPP) is a pruritic, painful, recurrent, and chronic dermatitis with limited therapeutic options. Objective To evaluate the efficacy and safety of apremilast for the treatment of Japanese patients with PPP and inadequate response to topical treatment. Methods This phase 2, randomized, double-blind, placebo-controlled study enrolled patients with Palmoplantar Pustulosis Area and Severity Index (PPPASI) total score ≥ 12 and moderate or severe pustules/vesicles on the palm or sole (PPPASI pustule/vesicle severity score ≥ 2) at screening and baseline with an inadequate response to topical treatment. Patients were randomized (1:1) to apremilast 30 mg twice daily or placebo for 16 weeks, followed by a 16-week extension phase during which all patients received apremilast. The primary endpoint was achievement of PPPASI-50 response (≥ 50% improvement from baseline in PPPASI). Key secondary endpoints included change from baseline in PPPASI total score, Palmoplantar Pustulosis Severity Index (PPSI), and patient’s visual analog scale (VAS) for PPP symptoms (pruritus and discomfort/pain). Results A total of 90 patients were randomized (apremilast: 46; placebo: 44). A significantly greater proportion of patients achieved PPPASI-50 at week 16 with apremilast versus placebo ( P = 0.0003). Patients receiving apremilast showed greater improvement in PPPASI at week 16 versus placebo (nominal P = 0.0013), as well as PPSI and patient-reported pruritus and discomfort/pain (nominal P ≤ 0.001 for all). Improvements were sustained through week 32 with apremilast treatment. The most common treatment-emergent adverse events included diarrhea, abdominal discomfort, headache, and nausea. Conclusions Apremilast treatment demonstrated greater improvements in disease severity and patient-reported symptoms versus placebo at week 16 in Japanese patients with PPP with sustained improvements through week 32. No new safety signals were observed. ClinicalTrials.gov NCT04057937. Supplementary Information The online version contains supplementary material available at 10.1007/s40257-023-00788-2.

Apremilast is a potentially useful treatment for severe palmoplantar pustulosis with extra‐palmoplantar symptoms

“…While both apremilast and guselkumab have been shown to be beneficial for PAO, 4 , 5 the efficacy of guselkumab for skin lesions may not be as compelling as apremilast; only approximately half of the patients achieved 50% improvement by guselkumab, whereas 78.3% of patients on apremilast achieved the same level of improvement in clinical trials. 6 , 7 , 8 In addition, a sub‐analysis by the Pharmaceuticals and Medical Devices Agency, the drug regulatory authority of Japan, suggested that the effectiveness of guselkumab in nonsmokers may be low. 9 Furthermore, biologics including guselkumab, are generally more economically burdensome than apremilast.…”