Evaluation of Ixekizumab Treatment for Patients With Pityriasis Rubra Pilaris: A Single-Arm Trial

Abstract

Importance: Pityriasis rubra pilaris is a rare and disabling cutaneous disease that is frequently recalcitrant to conventional therapies and appears to involve interleukin (IL)-17 overexpression.

Objective: To investigate the clinical response and safety of ixekizumab in treating pityriasis rubra pilaris.

Design, setting, and participants: Single-arm, investigator-initiated trial conducted in adult patients with moderate to severe pityriasis rubra pilaris at a single-center academic university from June 2018 to January 2020. A total of 41 patients were screened, 12 were enrolled, and 11 completed the full duration of therapy. A referred, consecutive sample was used during participant selection. The treatment period and primary outcome occurred over 24 weeks with additional patient follow-up through 36 weeks.

Intervention: Subcutaneous administration of ixekizumab, a humanized IgG4 antibody that binds IL-17A, at the US Food and Drug Administration-approved dosing schedule for treatment of psoriasis for 24 weeks.

Main outcomes and measures: The primary outcome was the mean change in Psoriasis Area and Severity Index at 24 weeks. Secondary outcomes included change in affected body surface area, quality of life, induction of sustained remission, and association of improvement with CARD14 genetic variations and cutaneous cytokine expression.

Results: A total of 12 white patients (mean [SD] age, 49.8 [15.1] years; 8 male [67%]) were enrolled between June 2018 and April 2019, with 11 completing the full course of intervention. The mean (SEM) improvements in Psoriasis Area and Severity Index, affected body surface area, and Dermatology Life Quality Index were 15.2 (2.1) (P < .0001), 29.8% (9.3%) (P = .009), and 9.5 (2.5) (P = .004), respectively. The 4 participants with the most improvement in Psoriasis Area and Severity Index at week 24 stayed in remission at week 36 (defined as lack of increase in Psoriasis Area and Severity Index from week 24 through week 36), off therapy. Relative dermal IL-17A expression decreased by a 1.9 log-fold change. No participants had known pathogenic CARD14 variations. There were no serious adverse events.

Conclusions and relevance: In this single-armed trial, ixekizumab was associated with reduced clinical signs and symptoms of pityriasis rubra pilaris in a subset of patients, including those in whom other systemic therapies have failed.

Trial registration: ClinicalTrials.gov Identifier: NCT03485976.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Haynes, Ortega-Loayza, Cassidy, Wang, and Liu and Mss. Strunck, Topham, and Kent reported receiving grants to their institution from Eli Lilly and Company during the conduct of the study. Dr Choate reported receiving grants from personal fees from Janssen and AbbVie outside the submitted work. Dr Greiling reported receiving grants from Eli Lilly and Company during the conduct of the study and grants from Janssen Scientific Affairs outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

Figure 2.. Clinician-Reported and Patient-Reported Outcome Measures at 24 Weeks

A, Mean Psoriasis Area and Severity Index (PASI) before and after therapy. Each point represents 1 participant. B, Aggregate response curves of the 12 participants. The overall score on the PASI ranges from 0 (clear skin) to 72 (worst possible disease). A PASI50 response indicates patients achieving a 50% or greater reduction from baseline. C, Mean affected body surface area before and after therapy. D, Mean Dermatology Life Quality Index (DLQI) on a 0-30–point scale before and after therapy. E, Mean usual itch and pain (F) over the last week measured by the patient on a 0-10–point numeric rating scale before and after therapy.

Figure 3.. Clinical Photography Before Treatment and 24 Weeks After Treatment With Ixekizumab

Clinical photography demonstrating representative clinical response in 3 of 11 study participants who completed the trial. Each side-by-side photograph pair reflects a different participant to include representation from the entire cohort. The left photos were taken at trial enrollment and the right photos were taken at the week-24 primary end point.

Figure 4.. Cutaneous Cytokines Before Treatment and 24 Weeks After Treatment With Ixekizumab

Fresh lesional skin biopsies were separated into epidermis and dermis. Relative mRNA levels were analyzed by quantitative real-time polymerase chain reaction in triplicate. Each dot on the graph represents the mean relative expression from 1 participant calculated by the delta-delta-Ct (ddCt) method. Week 0 (pretreatment) and week 24 (posttreatment) means were not significant except as indicated for dermis IL-17A.