52-Week Study Reveals Efficacy and Safety of Apremilast for Japanese Patients with Palmoplantar Pustulosis

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Researchers presented the results of a phase 3, randomized, placebo-controlled study¹ (NCT05174065) of apremilast (Otezla; Amgen) in Japanese patients with palmoplantar pustulosis at the 2024 Elevate-Derm West Conference. The data, presented in a poster,² highlighted its efficacy in this patient population, with improvements observed as early as 16 weeks and sustained through 52 weeks.

According to poster authors Okubo et al, the localized inflammatory disease has been especially difficult to manage in patients with moderate to severe symptoms, where topical therapies often fall short, and patients face limited systemic treatment options beyond topical corticosteroids. In Japan, its prevalence is estimated to be 0.12%, which is considered higher than in western countries like the US.³

Given the inflammatory basis of palmoplantar pustulosis and its similarity to other autoimmune skin conditions, researchers have explored apremilast, an oral phosphodiesterase 4 inhibitor, to assess its efficacy and safety over an extended period. Apremilast is already established in treating plaque psoriasis and psoriatic arthritis, showing effectiveness in reducing inflammation.

The study's primary objective was to evaluate the efficacy and safety of apremilast in treating Japanese patients with moderate tosevere palmoplantar pustulosis over 52 weeks.

The study employed a randomized, placebo-controlled, double-blind design, extending over 52 weeks to observe both primary and secondary efficacy outcomes. Adult patients with moderate to severe palmoplantar pustulosis, a Palmoplantar Pustulosis Area and Severity Index (PPPASI) score of at least 12, and a Psoriasis Area and Severity Index (PASI) score of less than 5, were enrolled in the study.

Exclusions included any history of plaque psoriasis, autoimmune disease, or concurrent use of biologics or systemic therapies within a specific timeframe.

Participants were randomized in a 1:1 ratio to receive either apremilast or a placebo for an initial 16 weeks. After this period, patients initially on the placebo were transitioned to apremilast from weeks 16 to 52. Apremilast was administered at a dose of 30 mg twice daily, which aligns with the dosing used in psoriasis treatment.

The efficacy endpoints focused on the PPPASI-50, PPPASI-75, and total PPPASI scores to determine clinical response rates, with additional assessments of pruritus and pain scores, as well as the Dermatology Life Quality Index (DLQI). Safety outcomes included monitoring for treatment-emergent adverse events across the study’s duration.

A significant percentage of patients receiving apremilast achieved the primary efficacy endpoint, PPPASI-75 (a 75% improvement in the PPPASI score), by week 16, with these improvements maintained through week 52. Additionally, researchers observed substantial improvements at the PPPASI-50 level, showing clinical responses in a large portion of patients as early as week 16.

Apremilast also significantly reduced pruritus and pain/discomfort, with effects observed as early as 2 weeks into treatment. These benefits persisted throughout the study, indicating durable symptom relief.

Furthermore, improvements in DLQI scores were maintained over time, indicating a marked positive impact on patients' day-to-day well-being.

The safety profile of apremilast was consistent with that seen in previous studies for other conditions, such as plaque psoriasis. The most common treatment-emergent adverse events were gastrointestinal-related issues like diarrhea and nausea, as well as headaches. These were generally mild to moderate in severity, and no unexpected safety signals emerged during the study.

References

1. A phase 3 study of apremilast in subjects with moderate to severe palmoplantar pustulosis. ClinicalTrials.gov identifier: NCT05174065. Updated November 5, 2024. Accessed November 7, 2024. https://clinicaltrials.gov/study/NCT05174065?tab=results
2. Okubo Y, Murakami M, Kobayashi S, et al. Efficacy and safety of apremilast for the treatment of Japanese patients with palmoplantar pustulosis: 52-week results from a phase 3, randomized, placebo-controlled study. Poster presented at: Elevate-Derm West Conference; November 7-10, 2024; Scottsdale, Arizona.
3. Ramcharran D, Strober B, Gordon K, et al. The epidemiology of palmoplantar pustulosis: an analysis of multiple health insurance claims and electronic health records databases. Adv Ther. 2023;40(11):5090-5101. doi:10.1007/s12325-023-02669-w

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