TOPLINE:

In a clinical trial, vixarelimab — a first-in-class human monoclonal antibody that targets oncostatin M (OSM) receptor beta, inhibiting interleukin 31 and OSM signaling, and addressing pruritus, inflammation, and fibrosis — significantly reduced pruritus and improved nodule clearance in patients with prurigo nodularis (PN).

METHODOLOGY:

• Researchers conducted a double-blind, placebo-controlled, phase 2b randomized trial involving 189 patients (mean age, 55.4 years; 60.3% women; 64.0% White, 18.0% Asian, 11.6% Black or African American, 6.3% Hispanic, 4.2% multiracial, and 2.1% American Indian or Alaska Native) with physician-diagnosed PN for at least 6 months across 72 centers in the US, Canada, Europe, and Asia from December 2020 to August 2023.
• Patients were randomly assigned to receive vixarelimab (n = 141) administered subcutaneously or placebo (n = 48). Treatment groups received subcutaneous vixarelimab every 4 weeks at doses of 540 mg (high dose), 360 mg (mid dose), or 120 mg (low dose) or placebo during the 16-week double-blind period. A 36-week open-label extension followed, during which all patients received 360 mg vixarelimab every 2 weeks.
• The primary endpoint was the percent change from baseline in the weekly mean Worst Itch Numeric Rating Scale (WI-NRS) score at 16 weeks.
• Secondary endpoints included the proportion of patients achieving at least a 4-point or 6-point reduction from baseline in weekly mean WI-NRS scores at week 16, the proportion of patients achieving PN investigator global assessment (PN-IGA) scores of 0 or 1 at week 16, and safety.

TAKEAWAY:

• Vixarelimab yielded significant reductions in mean WI-NRS scores across all doses compared with placebo at week 16; mean scores decreased by 56.2% with high-dose vixarelimab (P < .001), 51.0% with mid-dose vixarelimab (P < .001), and 33.0% with low-dose vixarelimab (P = .006) vs 14.5% with placebo.
• A higher proportion of patients achieved a clinically meaningful ≥ 4-point reduction in WI-NRS scores with vixarelimab than with placebo (high dose, 66.0%; mid dose, 61.7%; and low dose, 29.8% vs 16.7% with placebo), with significant differences for the high and mid doses (P < .001 for both), whereas a reduction of ≥ 6 points in WI-NRS scores was significant for all three vixarelimab doses vs placebo (high dose, 42.6%; mid dose, 23.4%; and low dose, 17.4% vs placebo, 2.1%; P < .001, P = .002, and P = .01 for high, mid, and low doses, respectively).
• PN-IGA scores of 0 or 1 were achieved by more patients in the vixarelimab groups (38.3% in the high-dose group, 29.8% in the mid-dose group, and 14.9% in the low-dose group) than in the placebo group (10.4%).
• Drug-related treatment-emergent adverse events were mild and included nasopharyngitis. No serious drug-related adverse events or deaths were reported during the study period.

IN PRACTICE:

“The clinical benefit of vixarelimab occurred rapidly and was sustained” throughout the 16-week double-blind and 36-week open-label extension periods, the authors wrote. “These results highlight the favorable benefit-risk profile of vixarelimab,” which is also being evaluated in studies of ulcerative colitis and idiopathic pulmonary fibrosis, they added.

SOURCE:

This study was led by Sonja Stӓnder, MD, Münster University Hospital, Münster, Germany, and was published online on December 17 in JAMA Dermatology.

LIMITATIONS:

The 16-week double-blind portion of the trial and the lack of placebo control during the open-label extension period introduced potential bias in the assessment of long-term efficacy. 

DISCLOSURES:

This study was funded by Kiniksa Pharmaceuticals. Four authors including Stӓnder reported receiving grants or personal fees from Kiniksa and had ties with various other sources. 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.