Howard Sofen, MD

A third of prurigo nodularis patients treated with vixarelimab showed major reductions of pruritus and reported clear or almost clear skin after 8 weeks, according to recent findings.¹

The chronic skin condition—known for the appearance of pruritic, hyperkeratotic lesions—interferes with many aspects of patients’ lives and was consequently viewed as a topic of concern.

Prurigo nodularis’s pathophysiology of pruritus continues to be opaque, but researchers more and more attribute it to type 2 inflammation and nonhistaminergic mediators.

Vixarelimab—a human monoclonal antibody—inhibits the signaling of 2 cytokine pathways at the same time, which have been implicated in pruritus, inflammation, and other effects. Its efficacy and its safety were tested in this study.

This research was authored by Howard Sofen, MD, from the Department of Medicine and Dermatology at the David Geffen UCLA School of Medicine.

“This phase 2a clinical trial with vixarelimab, a fully human monoclonal antibody with a novel mechanism of action targeting two primary drivers of pruritus and nodule formation (IL-31 and OSM type II receptor signalling), is the first reported clinical experience with an OSM beta receptor blocker in this disease,” Sofen and colleagues wrote.

Background

The investigators’ study was a placebo-controlled, randomized, phase 2a study following the previous phase 1 vixarelimab research for patients with atopic dermatitis, which showed strong tolerability, diminished loss of sleep compared to the placebo, and improvement in pruritus.²

The new study was done at 27 different outpatient research centers in both the US and Canada, with study participants recruited being ages 18 to 75. The inclusion criteria were as follows:

• A clinician’s diagnosis of prurigo nodularis re-confirmed by an independent review of medical photographs
• A minimum of 6 months duration of the condition
• Moderate-to-severe pruritus, which was defined as being a Worst Itch–Numeric Rating Scale (WI-NRS) rating of ≥7 during screening
• The existence of 10 pruritic nodules approximately 0.5 to 2 cm in size minimum, on 2 different anatomical locations at least
• The existence of normal-appearing skin between nodules, although atopic dermatitis was an exception as a comorbidity

The investigators randomly assigned the patients 1:1 to be treated placebo or with 360 mg of subcutaneous vixarelimab and they used the existence of atopy and sex, as well as block size 4 in the IWRS system, to stratify the participants.

They also based their atopy status-stratification on reports of greater prevalence of atopy in the population, as well as the possible effects of atopy in the immunopathologic process in the skin condition.

In total, 26 placebo patients and 23 vixarelimab patients had been randomized in the period between March of 2019 and January of 2020.

The research team’s main efficacy endpoint was reported to be the percent change in least squares (LS)-mean from baseline (PCFB) after 8 weeks in an average Worst Itch–Numeric Rating Scale (WI-NRS) score every week.

Findings

By 8 weeks, vixarelimab outcomes compared to placebo included LS-mean PCFB in WI-NRS score, −50.6% compared to −29.4% for the placebo (LS-mean difference [95% CI], −21.2% [−40.82, −1.60]; P=0.03); ≥4-point reduction in WI-NRS score, 52.2% (12 out of 23) compared to 30.8% (8 out of 26) (P=0.11).

Another outcome, PN-IGA score of 0 or 1, ended up being 30.4% (7 out of 23) versus 7.7% (2 out of 26) (P=0.03). They further reported that the LS-mean PCFB in pruritus VAS score was −54.4% compared to −32.6% (P=0.03).

Lastly, the investigators found that LS-mean PCFB sleep loss reduction (improvement) outcomes were −56.3% compared to −30.0% (P=0.02).

“Vixarelimab demonstrated rapid reduction of pruritus and achievement of clear/almost clear skin in one-third of the patients by Week 8,” they wrote. “Relief of itch and clearing of skin nodules represent two important potential therapeutic advances in the management of patients suffering from the debilitating disease Prurigo Nodularis.”

References:

1. Sofen H, Bissonnette R, Yosipovitch G, et al. Efficacy and safety of vixarelimab, a human monoclonal oncostatin M receptor β antibody, in moderate-to-severe prurigo nodularis: A randomised, double-blind, placebo-controlled, phase 2A study. eClinicalMedicine. Published online February 3, 2023. https://doi.org/10.1016/j.eclinm.2023.101826
2. Mikhak Z., Bissonnette R., Siri D., et al. KPL-716, anti-Oncostatin M receptor beta antibody, reduced pruritus in atopic dermatitis.J Invest Dermatol. 2019; 139: S96. https://doi.org/10.1016/j.jid.2019.03.636