Efficacy and Safety of Guselkumab in Japanese Patients With Palmoplantar Pustulosis: A Phase 3 Randomized Clinical Trial.

Abstract

Importance\nPalmoplantar pustulosis (PPP) causes erythematous, scaly plaques with recurrent sterile pustules refractory to treatment and with few randomized clinical trials conducted. Evidence points to involvement of interleukin 23 in the pathogenesis of PPP.\n\n\nObjective\nTo determine the efficacy and safety of guselkumab, an anti-IL-23 monoclonal antibody, in Japanese patients with PPP.\n\n\nDesign, Setting, and Participants\nA phase 3 randomized clinical trial was conducted from December 15, 2015, to December 12, 2017. A total of 159 enrolled patients (aged ≥20 years) had an inadequate response to conventional therapies, with a diagnosis of PPP for 24 or more weeks before screening. Intention-to-treat analysis was performed.\n\n\nInterventions\nSubcutaneous injections of guselkumab, 100 or 200 mg, at weeks 0, 4, and 12, and every 8 weeks thereafter were administered; placebo was given at weeks 0, 4, and 12.\n\n\nMain Outcomes and Measures\nChanges from baseline in PPP Area and Severity Index (PPPASI) score (possible score range, 0-72, with higher scores indicating greater area and severity), PPP severity index (PPSI) score (possible score range, 0-12, with higher scores indicating greater severity), and proportion of PPPASI-50 (≥50% reduction) responders at weeks 16 and 52 were assessed. Safety was monitored through week 52.\n\n\nResults\nA total of 159 patients (mean [SD] age at diagnosis, 46.8 [11.9] years; 126 women [79.2%]) were enrolled. Treatment groups comprised guselkumab, 100 mg (n\u2009=\u200954), guselkumab, 200 mg (n\u2009=\u200952), or placebo (n\u2009=\u200953). Both guselkumab groups demonstrated significant improvement in least-squares mean changes in PPPASI score compared with placebo: -15.3 and -11.7 in the guselkumab 100-mg and 200-mg groups, respectively, and -7.6 in the placebo group (difference [SE] vs placebo: -7.7 [1.7] in the 100-mg group, P\u2009<\u2009.001; 95% CI, -11.00 to -4.38; and -4.1 [1.7] in the 200-mg group, P\u2009<\u2009.017; 95% CI, -7.47 to -0.75]). Least-squares mean changes in PPSI score showed significant improvement in both guselkumab groups (100 mg: -2.0 [0.5]; P\u2009<\u2009.001; 95% CI, -2.96 to -0.95; 200 mg: -1.0 [0.5; P\u2009=\u2009.04; 95% CI, -2.06 to -0.03). A significantly higher proportion of patients in the guselkumab 100-mg group (31 [57.4%]) achieved a PPPASI-50 response at week 16 vs placebo (18 [34.0%]; P\u2009=\u2009.02); however, the result was not significant for the guselkumab 200-mg group (19 [36.5%]) vs placebo; P\u2009=\u2009.78). Each efficacy end point improved consistently through week 52. Health-related quality of life improved significantly as indicated by a reduction in the Dermatology Life Quality Index score (100 mg: -2.6; 95% CI, -4.0 to -1.2; P\u2009<\u2009.001; 200 mg: -1.6; 95% CI, -3.1 to -0.2; P\u2009=\u2009.03). Serious treatment-emergent adverse events were observed in 8 patients (placebo group, 2 of 53 [3.8%]; combined guselkumab group, 6/157≠10.5%). No serious infections were reported.\n\n\nConclusions and Relevance\nTargeting interleukin 23 with guselkumab may be an effective and safe treatment option for a recalcitrant disease such as PPP.\n\n\nTrial Registration\nClinicalTrials.gov identifier: NCT02641730.