VIENNA — A novel monoclonal antibody that binds to the interleukin (IL)-4 receptor, thereby blocking both IL-4 and IL-13 mediated signaling, showed sustained suppression of itch and other symptoms of prurigo nodularis in a multicenter placebo-controlled trial. 

At 24 weeks, “deep pruritus relief was achieved in nearly 75% of patients, and it was sustained during the subsequent 28-week open-label extension,” reported Jianzhong Zhang, MD, professor and chairman of dermatology at Peking University People’s Hospital, Beijing, China.

In this phase 3 trial, 412 patients with prurigo nodularis inadequately controlled with topical corticosteroids were randomized to 450 mg of the experimental agent oturkibart or placebo administered subcutaneously every 2 weeks. 

The Chinese study was a latebreaker presentation at the European Academy of Dermatology and Venerology (EADV) 2026 Congress. 

Itch Reduction Is Primary Endpoint 

The primary endpoint at the end of the 24-week blinded period was a 4-point or greater reduction in the weekly average Worst Itch Numeric Rating Scale (WI-NRS). Scores of 7 or higher on a scale of 0-10 (worst imaginable) are considered a severe presentation. 

Based on the proportion of patients who met the primary endpoint, the advantage of oturkibart over placebo at 24 weeks was not only highly significant overall (74.5% vs 29%; P < .0001), but the difference between treatment and placebo was even greater in the subgroup of 61 patients (14.8%) who continued to take topical steroids or topical calcineurin inhibitors during the blinded period (79.7% vs 13.7%; P < .0001).

In the open-label extension, the proportion of patients reaching at least a 4-point improvement in the WI-NRS continued to increase. From 74.5% at week 24, it reached 95.5% by week 52. The placebo group, starting at 29.2% at 24 weeks, nearly caught up after switching to oturkibart, reaching 90.6% at 52 weeks. 

Lesion clearance, evaluated with an Investigator Global Assessment (IGA) rating of 0 or 1 (clear or almost clear), was more common in the oturkibart arm than the placebo arm. although lesion clearance occurred more slowly than itch relief. The curves began to separate at week 4, but the difference did not reach significance until week 15 (16.9% vs 8.0%; P < .01). 

The steady climb in IGA 0/1 responders over the 24-week blinded phase favored oturkibart at 24 weeks (34.7% vs, 11.1%; P < .001), and as was seen for control of itch, further gains in lesion clearance over the extension phase of the study. Patients who remained on oturkibart maintained higher IGA 0/1 response than those who switched from placebo at week 52 (66.9% vs 49.2%).

Quality of life was evaluated using the Dermatology Life Quality Index (DLQI) and the Hospital Anxiety and Depression Scale (HADS). Scores on both quality-of-life instruments improved steadily among patients initially randomized to oturkibart during the blinded phase of the study and among those who switched from placebo to oturkibart. 

Placebo Group Responds Rapidly After Switch 

“After switching from placebo to oturkibart, the magnitude of improvements in DLQI and HADS increased markedly, approaching the continuous oturkibart group by week 52, but the improvement among those maintained on oturkibart also climbed further relative to week 24,” Zhang said.

Investigators also evaluated the proportion of patients with complete resolution of itch (WI-NRS score ≤ 1) and those with a major response (WI-NRS score ≤ 2), which were 55.1% and 76.7%, respectively, in the entire study population at week 52. 

Outcomes were also evaluated in study participants (25.5%) who had not achieved at least a 4-point reduction in WI-NRS by the end of the 24-week blinded phase. This subgroup was characterized as slow responders on the basis of the 24-week data, but most (81.6%) achieved the primary endpoint of at least a 4-point improvement of WI-NRS at week 52. Of the slow-responder subgroup, 51.8% achieved skin clearance as defined by IGA score of 0 or 1 at week 52.

During the blinded phase, no noteworthy differences in adverse events were observed between the oturkibart and placebo arms. Serious adverse events (4.9% vs 5.3%) and adverse events leading to discontinuation (1.5% vs 1.9%) were numerically lower in the oturkibart arm.

Reviewing adverse events of interest, Zhang reported that rates of injection-site reactions (2.9% vs 2.4%), infection (36.9% vs 33.0%), herpes-related events (0.5% vs 2.4%), and conjunctivitis (1.9% vs 1.0%) as similar at 24 weeks.

If it receives regulatory approval, oturkibart will be the second monoclonal antibody with the anti-IL-4 receptor mechanism of action to produce clinical benefit in patients with prurigo nodularis. The first monoclonal antibody to be approved for this indication was dupilumab (Dupixent).

No controlled studies comparing the two agents have been done yet. Nonetheless, Peter Wolf, MD, professor and chair of the Department of Dermatology at the University of Graz in Austria, asked Zhang whether there was any reason to suspect that they might differ clinically on the basis of data so far. Wolf pointed out the very low rate of conjunctivitis (1.9%) observed with oturkibart in this study relative to the 10%-15% typically reported for dupilumab in other trials. 

Zhang responded that not much can be said yet about the safety and efficacy of oturkibart relative to dupilumab, but these agents cannot be considered interchangeable without head-to-head studies. 

He noted that that the low rate of conjunctivitis is a marked difference between this agent and dupilumab, but he could not offer a theory about the reason for this difference and added that confirmation of it awaits further studies.

Zhang reported financial relationships with AbbVie, Bristol-Myers Squibb, Cutia Genrix Bio, InventisBio, Jemincare, Jiangsu Hengrui Medicine, Highlight, Innovent Biologics, Longwood, Eli Lilly, LEO Pharma, Novartis, Pfizer, Sanofi, Shenzhen Kangzhe, Takeda, Theoderma, TopAlliance, Viatris, Xian Janssen, and Zelgen. Wolf reported no potential conflicts of interest. 

Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including dermatology and oncology, for several decades.