Efficacy and safety of guselkumab in European patients with palmoplantar pustulosis: A multi-center, single-arm clinical trial (GAP study)

Abstract

Background: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disorder that affects palms and soles. Patients suffer significant pain, itching, and daily activity impairment. Guselkumab, an interleukin-23 inhibitor, has been approved for PPP treatment in Japan. However, there is no effective therapy licensed for PPP in Europe and the USA.

Objective: To explore the efficacy and safety of guselkumab in patients with moderate-to-severe PPP in the Caucasian population.

Methods: A multicenter, single-arm, phase II study involving 50 patients with moderate-to-severe PPP treated with 100 mg guselkumab subcutaneously for 24 weeks was conducted (GAP). Primary endpoint was the reduction of palmoplantar-pustulosis psoriasis area and severity index (PPPASI) at week 24 compared to baseline. Secondary endpoints included physician-assessed and patient-reported measures. Serum samples were taken for exploratory studies.

Results: The primary endpoint was met with a significant median PPPASI reduction by 59.6% at week 24 compared to baseline (P < .001). The proportions of patients achieving PPPASI-50 and PPPASI-75 at week 24 were 66.0% and 34.0%, respectively. Median dermatology life quality index dropped from 15 at baseline to 5 at week 24 (P < .001). Week 4 changes in interleukin-19 serum levels predicted week 24 clinical response.

Conclusion: Guselkumab may be a promising therapeutic option for PPP in Caucasian patients.

Keywords: IL-23; PPPASI; guselkumab; interleukin-19; multicenter trial; palmoplantar pustular psoriasis; palmoplantar pustulosis; smoking.

Fig 1

Patient disposition flowchart. A total of 55 patients were screened. A, Three patients did not meet the inclusion criteria: 2 patients had a palmoplantar pustulosis area and severity index (PPPASI) <12 at baseline and another patient had a serum creatinine ≥1.5 mg/dL. B, One patient met an exclusion criterion (severe hepatic dysfunction). C, One patient withdrew consent. Six patients terminated the study early: (D) Three patients have withdrawn the consent, one on visit 2, one on visit 3, and one on visit 4. E, Two patients discontinued the study because of the occurrence of treatment-emergent adverse events: 1 patient due to tinea pedis and worsening of palmoplantar pustulosis (PPP), the other one due to suspected drug reaction to guselkumab manifesting as nausea, vomiting, arthralgia, and injection-site reaction. F, One patient discontinued because of lack of efficacy.

Fig 2

Guselkumab improves clinical scores and patient-reported outcomes in palmoplantar pustulosis (PPP) patients. A, Box-whisker plot of palmoplantar pustulosis area and severity index (PPPASI) values of guselkumab-treated patients (full-analysis-set population) over the study period (baseline [wk0], wk4, wk12, and wk24 [end of study]). Missing data were handled using baseline-observation-carried-forward (BOCF) method. The line in the middle of the box represents the median (second quartile, Q2), the lower and upper margins of the box represent the first (Q1) and third (Q3) quartile, respectively, and the ends of the whiskers represent the most extreme lower and upper values within Q3+1.5∗(Q3-Q1) and Q1-1.5∗(Q3-Q1), respectively). The diamond denotes the mean, circles denote outliers and asterisks denote a significant difference (∗∗∗: P < .001; ∗∗: P < .01) of PPPASI change from baseline. B, Proportions and absolute numbers of guselkumab-treated patients over the study period who achieved at least a 50% and a 75% improvement of the PPPASI. The BOCF method was used. C, Percentage changes (±SD) in individual skin alterations accounting for the PPPASI (degree of pustules, erythema, scaling) in guselkumab-treated patients at wk4, wk12, and wk24 relative to baseline. Stars indicate the significance of changes from baseline (∗∗∗: P < .001; ∗∗: P < .01). D, Box-whisker plot of absolute dermatology life quality index (DLQI) values of guselkumab-treated patients over the study period. The BOCF method was used. For description of box-whisper plots see (A). Asterisks denote a significant difference (∗∗∗: P < .001; ∗∗: P < .01) of the percent change from baseline. E, Box-whisker plot of pain values (determined by a numeric rating scale (NRS)] of guselkumab-treated patients over the study period. The BOCF method was used for description of box-whisper plots see (A). Asterisks denote a significant difference (∗∗∗: P < .001). F, Box-whisker plot of NRS pruritus values of guselkumab-treated patients over the study period. The BOCF method was used. For description of box-whisper plots see (A). Asterisks denote a significant difference (∗∗: P < .01).

Fig 3

Clinical images and palmoplantar pustulosis area and severity index (PPPASI) of 4 representative patients at baseline and wk24. A, Palms of a 45-year-old female patient at baseline (PPPASI 22) and at wk24 (PPPASI 3). B, Plantae of a 52-year-old female patient at baseline (PPPASI 26) and at wk24 (PPPASI 11). C, Plantae of a 58-year-old female patient at baseline (PPPASI 35) and at wk24 (PPPASI 16). D, Plantae of a 59-year-old male patient at baseline (PPPASI 17) and at wk24 (PPPASI 2).

Fig 4

The interleukin (IL)-19 serum level may be a predictive biomarker for the treatment response of PPP patients to guselkumab. A, Box-whisker plot of absolute IL-19 serum levels of guselkumab-treated PPP patients (full-analysis-set population; missing values have not been imputed; wk0 (baseline): n = 50, wk4: n = 48, wk12: n = 47, and wk24: n = 44) and 14 healthy control participants. The line in the middle of the box represents the median (second quartile, Q2), the lower and upper margins of the box represent the first (Q1) and third (Q3) quartile, respectively, and the ends of the whiskers represent the most extreme lower and upper values within Q3+1.5∗(Q3-Q1) and Q1-1.5∗(Q3-Q1), respectively). The diamond denotes the mean and circles denote outliers. Asterisks denote a significant difference compared to heathy control participants (blue) or study patients at wk0 (black) (∗∗∗: P < .001, ∗∗: P < .01, ∗: P < .05; ns: not significant). B, Correlation between the absolute changes in IL-19 serum level between wk4 and baseline versus the absolute changes in PPPASI between wk24 and baseline in guselkumab-treated patients (missing values have not been imputed, n = 43). Spearman correlation coefficient and P value are shown.