Vixarelimab Trial Reports Itch and Lesion Benefit in Prurigo Nodularis

Key Takeaways

• Greater week 16 itch reduction was observed with vixarelimab than placebo, with the clearest effects in the 540-mg and 360-mg groups.
• Clinically meaningful WI-NRS responder rates and PN-IGA clear or almost clear responses were higher with vixarelimab than with placebo.
• Adverse events were more frequent with vixarelimab but were mostly mild, no fatal or serious drug-related TEAEs were reported, and trough concentrations reached steady state by week 12.

In adults with moderate to severe prurigo nodularis, monthly subcutaneous vixarelimab was associated with larger week 16 itch reductions than placebo during the blinded period. In the 540-mg group, weekly mean WI-NRS declined 56.2% versus 14.5% with placebo in a phase 2b randomized clinical trial in JAMA Dermatology. Lesion responses were also higher with vixarelimab, although detailed responder results varied across dose groups, over the same 16-week treatment period.

This multicenter, double-blind, placebo-controlled phase 2b study ran at 72 centers across the US, Canada, Europe, and Asia, with participant follow-up to about 56 weeks. It enrolled adults aged 18 to 80 years with prurigo nodularis for at least 6 months, moderate to severe pruritus, and 20 or more nodules in two locations. Participants were randomized 1:1:1:1 to subcutaneous vixarelimab 540 mg, 360 mg, 120 mg, or placebo every 4 weeks during the 16-week double-blind period. In the 36-week open-label extension, all participants who entered that phase received vixarelimab 360 mg every 2 weeks. Overall, 189 of 190 randomized participants received treatment. Mean age was 55.4 years, 60.3% were female, and baseline WI-NRS and PN-IGA averaged 8.5 and 3.3; endpoints included week 16 WI-NRS change, itch responders, and PN-IGA 0 or 1.

At week 16, least-squares mean WI-NRS changes were -56.2% with 540 mg, -51.0% with 360 mg, -33.0% with 120 mg, and -14.5% with placebo. The corresponding P values for the active groups were <.001, <.001, and .006. For a 4-point or greater WI-NRS improvement, response rates were 66.0%, 61.7%, 29.8%, and 16.7%, with P values of <.001, <.001, and .12 in dose order. For 6-point or greater improvement, rates were 42.6%, 23.4%, 17.4%, and 2.1%, with P values of <.001, .002, and .01. Mean WI-NRS improvements appeared within 1 week.

PN-IGA scores of 0 or 1 at week 16 were reported in 38.3%, 29.8%, and 14.9% with 540, 360, and 120 mg, versus 10.4% with placebo. Sleep loss visual analog scale and ItchyQoL were also assessed, but the main reported differences were in itch and lesion measures. Improvements were sustained through the open-label extension, and participants previously assigned to placebo improved after switching to vixarelimab 360 mg every 2 weeks. Because that phase lacked placebo control, longer-term findings remained descriptive rather than comparative.

During the double-blind period, TEAEs occurred in 74.5%, 61.7%, 44.7%, and 54.2% of the 540-mg, 360-mg, 120-mg, and placebo groups; drug-related rates were 29.8%, 21.3%, 10.6%, and 10.4%. Most events were mild, common events included headache, eczema, and fatigue, and no fatal or serious drug-related TEAEs were reported. Trough concentrations rose with repeated dosing and reached steady state by week 12 in the vixarelimab trial in prurigo nodularis, and serious TEAEs that occurred were not considered drug related. Confirmed treatment-emergent antibodies occurred in 33 participants, or 23.4%, including 7, or 5.0%, with high titers. The authors described dose-dependent benefit and a favorable safety profile, while noting the 16-week blinded phase and uncontrolled extension.