TOPLINE:

In a small phase 2 trial, an oral deuterated pentoxifylline analog (PCS499) was well tolerated and was associated with improvements in lesion activity, quality of life, and complete ulcer healing in adults with necrobiosis lipoidica (NL).

METHODOLOGY:

• Researchers conducted a phase 2, open-label, nonrandomized trial involving 12 adult women aged 19-66 years (median age, 41 years; all White) with biopsy-confirmed NL from January 2019 to February 2020. Most (10 women) had diabetes.
• Participants were treated with PCS499 (an oral deuterated analog of pentoxifylline, which has anti-inflammatory and hemorheologic effects) at a dose of 900 mg twice daily for 6 months, with an optional 6-month extension, at the University of Pennsylvania and the University of Pittsburgh.
• The primary outcome was safety, assessed through adverse event (AE) monitoring, laboratory testing, and electrocardiography.
• Exploratory efficacy endpoints included changes in Investigator Global Assessment, Physician Global Assessment (PGA), Patient Global Assessment (PtGA), NL Color and Ulcer Scale (NLCUS), Dermatology Life Quality Index (DLQI), and Skindex-29 scores.

TAKEAWAY:

• Overall, 10 patients (83%) experienced 30 AEs; seven patients (58%) reported mild treatment-related AEs, and two patients (17%) required dose reduction. The most common AEs were mild gastrointestinal symptoms (33%); no serious AEs or deaths occurred. Two patients stopped treatment during the first treatment phase and one during the extension because of mild alopecia, considered probably related to treatment.
• The two participants with ulcerated NL achieved more than a 75% reduction in the ulcerated area by 6 months and complete closure during the extension period.
• Among the 10 participants who completed treatment, five (50%) achieved clear or almost clear IGA status (IGA of 0 or 1) in a median time of 111 days, and improvements were observed in IGA activity (median change, -1.5; P = .03).
• Clinical improvements from baseline to 6 months were noted in PGA (median change, -1.3; P = .04), NLCUS inflammation or color (median change, -1.0; P = .02), and NLCUS induration (median change, -1.0; P = .04). Skindex-29 function scores also improved (median change, -14.6; P = .05), with “favorable trends” in DLQI and PtGA scores.

IN PRACTICE:

“Overall, PCS499 demonstrated favorable tolerability and efficacy signals in NL, including clinically meaningful improvement in ulcerated disease, supporting evaluation in larger, controlled studies,” the authors of the study concluded. There are currently no FDA-approved treatments for NL, which is often associated with diabetes, they noted.

SOURCE:

The study was led by Ayelet I. Rubenstein, Perelman School of Medicine, University of Pennsylvania, Philadelphia, and was published online on April 29 as a brief report in JAMA Dermatology.

LIMITATIONS:

The study enrolled a small number of participants, was open-label and nonrandomized, and lacked a comparator arm, limiting causal inference. The findings have limited generalizability to other demographic groups.

DISCLOSURES:

The study was funded by Processa Pharmaceuticals, which is developing PCS499 for NL. Four authors reported being employees of the company. Some authors reported receiving personal fees, grants, or other funding from various sources, including Processa Pharmaceuticals. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.