Immediate response to apremilast in patients with palmoplantar pustulosis: a retrospective pilot study

Abstract

Background: Recent case reports have shown the efficacy of apremilast for the treatment of palmoplantar pustulosis (PPP). However, no study has statistically analyzed the clinical efficacy of oral apremilast in patients with PPP.

Objectives: To evaluate the effectiveness of apremilast, a phosphodiesterase 4 inhibitor, for PPP.

Materials and methods: Among 13 patients who were diagnosed with PPP, 10 patients with PPP with either palmoplantar pustules (>1 mm diameter) or sternoclavicular joint pain were retrospectively analyzed.

Results: Palmoplantar Pustulosis Area and Severity Index (mean ± SD: baseline, 13.4 ± 9.5 vs. after treatment, 5.1 ± 5.6; P = 0.013) and the number of pustules measuring > 1 mm in diameter (3.9 ± 3.9 vs. 1.3 ± 1.9; P = 0.029) significantly improved in 2 (±1) weeks. Moreover, the Dermatology Life Quality Index (9.7 ± 7.0 vs. 3.3 ± 3.6; P = 0.009) and palmoplantar itching (visual analog scale [VAS] score) (5.6 ± 3.5 vs. 2.1 ± 2.2; P = 0.026) significantly improved in 2 weeks, whereas VAS scores of palmoplantar pain (4.8 ± 4.4 vs. 1.1 ± 2.4; P = 0.081) and sternoclavicular joint pain (3.2 ± 3.8 vs. 2.0 ± 2.6; P = 0.194) did not significantly improve. Diarrhea was observed in 60.0% of our patients.

Conclusion: Our study demonstrated that apremilast can effectively treat cutaneous manifestations and arthralgia in Japanese patients with PPP who had apparent pustules and/or clavicular-sternocostal arthralgia. Owing to the retrospective design of the study and a small sample size, placebo-controlled clinical trials with a larger number of patients are warranted to confirm the efficacy of apremilast for treatment of PPP.

Figure 1

Chronological changes in Palmoplantar Pustulosis Area and Severity Index (PPPASI) score and pustule count (>1 mm) after the initiation of oral apremilast. Both PPPASI score and pustular count were significantly improved in 2 (±1) weeks. Exacerbation because of discontinuation of oral apremilast is observed in case 10 (black arrowhead); however, PPPASI score and pustule count immediately responded to resumption of oral apremilast. (a) Changes in PPPASI score at week 2 (±1) in each patient. PPPASI score improved in eight patients in 2 (±1) weeks and was slightly exacerbated in one patient. (b) The entire course of PPPASI score within 24 weeks after the initiation of apremilast. (c) Changes in the pustule count at week 2 (±1) in each patient. (d) The entire course of pustule counts within 24 weeks. Paired t‐test, *P < 0.05; **P < 0.01

Figure 2

Clinical pictures of cases 1 and 6. Case 1 (upper row): baseline, 2 weeks, and 8 weeks later. Case 6 (lower row): baseline, 10 days, and 12 weeks later

Figure 3

Kaplan–Meier analysis at 50%, 75%, and 90% achievement rates in PPPASI score and pustular count. Achievement rates of 50%, 75%, and 90% improvement in PPPASI scores (PPPASI‐50/75/90%) and achievement rates of 50%, 75%, and 90% improvement in pustule count (PC‐50/75/90%) are compared. Improvement in pustule count preceded improvement in PPPASI score in all three graphs. The Kaplan–Meier method only captures the first occurrence of the study endpoints not transient disease exacerbations. PPPASI, Palmoplantar Pustulosis Area and Severity Index

Figure 4

Chronological changes in subjective scores of skin manifestations. (a) Mean DLQI score significantly decreased at week 2. (b) Mean VAS score for palmoplantar itching. (c) Mean VAS score for palmoplantar pain. (d) Mean VAS score for sternoclavicular joint pain. The mean palmoplantar itching was significantly improved at week 2. The mean palmoplantar pain and mean sternoclavicular joint pain were improved from the baseline values at each timepoint; however, the changes were not significant. Sternoclavicular joint pain appeared to improve slowly compared to other cutaneous manifestations. Paired t‐test with Bonferroni adjustment: *P < 0.05, **P < 0.01. DLQI, Dermatology Life Quality Index; VAS, visual analog scale