Exploratory Efficacy Evaluation of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: 32-Week Results from a Phase 2, Randomized, Placebo-Controlled Study

Dermatol Ther (Heidelb) https://doi.org/10.1007/s13555-024-01195-z ORIGINAL RESEARCH Exploratory Efficacy Evaluation of Apremilast for the Treatment of Japanese Patients with Palmoplantar Pustulosis: 32‑Week Results from a Phase 2, Randomized, Placebo‑Controlled Study Yukari Okubo Yayoi Tada · Tadashi Terui · Satomi Kobayashi · Shigetoshi Sano · Akimichi Morita · Shinichi Imafuku · · Masatoshi Abe · Masafumi Yaguchi · Takeshi Kimura · Junichiro Shimauchi · Wendy Zhang · Hamid Amouzadeh · Masamoto Murakami Received: April 2, 2024 / Accepted: May 24, 2024 © The Author(s) 2024 ABSTRACT Introduction: Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis that greatly impacts functioning and quality of life and can be difficult to treat. Approved treatment options for PPP are limited, and many patients do not fully respond to current treatments. Methods: This was a randomized, doubleblind, placebo-controlled, phase 2 study in Japanese patients with moderate to severe PPP Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s13555-024-01195-z. Y. Okubo (*) Tokyo Medical University, 6 Chome‑7‑1 Nishishinjuku, Shinjuku, Tokyo 160‑0023, Japan e-mail: T. Terui Nihon University School of Medicine, Tokyo, Japan S. Kobayashi Seibo International Catholic Hospital, Tokyo, Japan S. Sano Kochi Medical School, Kochi University, Kochi, Japan A. Morita Nagoya City University, Nagoya, Japan and inadequate response to topical treatment. Patients were randomized 1:1 to receive apremilast 30 mg twice daily or placebo for 16 weeks followed by an extension phase where all patients received apremilast through week 32. PPP Area and Severity Index (PPPASI), modified PPPASI (which evaluates pustules and vesicles separately), and Palmoplantar Severity Index (PPSI) total scores and subscores (erythema, pustules/vesicles, and desquamation/scales) were evaluated over 32 weeks of apremilast treatment. Achievement of ≥ 50% improvement in PPPASI (PPPASI-50) was evaluated at week 16 among baseline demographic and clinical characteristic subgroups. S. Imafuku Fukuoka University, Fukuoka, Japan Y. Tada Teikyo University, Tokyo, Japan M. Abe Sapporo Skin Clinic, Sapporo, Japan M. Yaguchi · T. Kimura · J. Shimauchi Amgen KK, Tokyo, Japan W. Zhang · H. Amouzadeh Amgen Inc., Thousand Oaks, CA, USA M. Murakami Atsuta Skin Clinic, Nagoya, Japan Vol.:(0123456789) Dermatol Ther (Heidelb) Results: At week 16, improvements in total score and subscores for PPPASI, modified PPASI, and PPSI, as well as rates of PPPASI-50 were at least moderately greater with apremilast than placebo. Mean PPPASI total score decreased by − 68.3% from baseline to week 32 with continued apremilast treatment. At week 32, mean change from baseline in PPPASI/modified PPPASI subscores ranged from − 58.5% to − 77.0% with apremilast. At week 32, PPSI total score for physician and patient assessments decreased by − 51.3% and − 40.0%, respectively, with continued apremilast treatment. PPPASI-50 response at week 16 was greater with apremilast versus placebo in most demographic and baseline characteristic subgroups. Conclusions: Improvements in all PPPASI and PPSI total scores and subscores observed with apremilast over 16 weeks were maintained through 32 weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Rates of PPPASI-50 response at week 16 were mostly consistent across patient subgroups. ClinicalTrials.gov: NCT04057937. Keywords: Apremilast; Palmoplantar pustulosis; Phase 2; PPPASI Key Summary Points Approved treatment options for palmoplantar pustulosis (PPP) are limited. Improvements in PPP overall disease severity observed with apremilast over 16 weeks were maintained for 32 weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Improvements in all signs and findings of PPP (i.e., erythema, pustules, vesicles, and desquamation/scales) were observed over 32 weeks of apremilast treatment as assessed by both the physician and the patient. Apremilast showed consistent benefit over placebo at week 16 across demographic and disease characteristic subgroups. INTRODUCTION Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis [1]. It is characterized by a combination of intraepidermal vesicles, pustules, erythema, and scales/desquamation located on the palms and soles [2, 3]. As a result of the location of lesions, PPP can greatly limit a patient’s functional ability and can negatively impact quality of life [4]. PPP can also be difficult to treat. Topical treatments such as corticosteroids, active vitamin D3 ointments, and phototherapy are common treatments for PPP [1]. The efficacy of topical treatments is limited, however, because the thicker stratum corneum of the palms and soles acts as a barrier. There is an unmet need for improved treatments for PPP in patients whose disease is not adequately controlled by topical treatments. Apremilast is an oral phosphodiesterase 4 inhibitor that has shown efficacy for the treatment of psoriatic disease, including palmoplantar psoriasis [5–14]. We previously reported improvements in disease severity and patientreported symptoms after 16 and 32 weeks of apremilast treatment in Japanese patients with PPP [15]. Here we assess modified PPP Area and Severity Index (PPPASI) and Palmoplantar Severity Index (PPSI) total scores and subscores evaluated by the physician and the patient over 32 weeks of apremilast treatment as well as a subgroup analysis of achievement of ≥ 50% improvement in PPPASI (PPPASI-50) at week 16 among subgroups of patients stratified by baseline demographics and disease characteristics. METHODS Study Design Study design and inclusion criteria have been reported in detail [15]. Briefly, this was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2 trial of apremilast in Japanese patients with PPP. Patients were randomized 1:1 to receive apremilast 30 mg twice daily or placebo for 16 weeks. After week 16, Dermatol Ther (Heidelb) patients initially randomized to apremilast continued on apremilast and those initially randomized to placebo switched to apremilast (placebo/apremilast) through week 32 during the active treatment phase. This study was conducted in accordance with International Council for Harmonization E6 and the ethical principals that are outlined in the Declaration of Helsinki. The study protocol and all amendments, the informed consent form, and any accompanying materials provided to the patients were reviewed and approved by an institutional review board or independent ethics committee at each study center (Online Resource 1). Patients provided written informed consent prior to study procedures. Key Inclusion Criteria Patients were adults (≥ 20 years of age) with a diagnosis of PPP for at least 24 weeks before screening. Key inclusion criteria were a PPPASI (...truncated)