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. This was a randomized, double-blind, placebo-controlled, phase2 study in Japanese patients with moderate to severe PPP and inadequate response to topical treatment. Patients were randomized 1:1 to receive apremilast 30mg twice daily or placebo for 16weeks followed by an extension phase where all patients received apremilast through week32. 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 32weeks of apremilast treatment. Achievement of ≥ 50% improvement in PPPASI (PPPASI-50) was evaluated at week16 among baseline demographic and clinical characteristic subgroups. At week16, 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 week32 with continued apremilast treatment. At week32, mean change from baseline in PPPASI/modified PPPASI subscores ranged from - 58.5% to - 77.0% with apremilast. At week32, PPSI total score for physician and patient assessments decreased by - 51.3% and - 40.0%, respectively, with continued apremilast treatment. PPPASI-50 response at week16 was greater with apremilast versus placebo in most demographic and baseline characteristic subgroups. Improvements in all PPPASI and PPSI total scores and subscores observed with apremilast over 16weeks were maintained through 32weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Rates of PPPASI-50 response at week16 were mostly consistent across patient subgroups. GOV: NCT04057937.