Rocatinlimab a new treatment option for head and neck AD?

Rocatinlimab improved disease severity in patients with moderate-to-severe head and neck atopic dermatitis (H&N AD), a post hoc analysis of a phase IIb trial has shown.

“The H&N region is more exposed and vulnerable to environmental triggers and can be harder to treat than any other body parts … [Thus, AD in this region] puts an emotional toll in patients,” said Dr Emma Guttman-Yassky from Icahn School of Medicine at Mount Sinai, New York City, New York, US, at EADV 2022.

“Rocatinlimab is a first-in-class anti-OX40 monoclonal antibody that targets important pathways underlying AD pathogenesis,” she continued. It reduces the number of OX40-expressing T-cells and could mitigate local and systemic inflammation driving AD pathology. [J Dermatol Sci 2020;99:82-89] “[Rocatinlimab] may thus be an effective AD treatment … including hard-to-treat, resistant H&N manifestations,” said Guttman-Yassky.

The study comprised 274 adults with chronic moderate-to-severe AD (mean EASI* >30) who had had inadequate response or intolerance to topical AD therapy. Of these, 219 patients with H&N AD (mean EASI >3) were included on post hoc analysis. Participants were randomized 1:1:1:1:1 to receive SC rocatinlimab 150 or 600 mg Q4W, 300 or 600 mg Q2W for 36 weeks, or placebo for the first 18 weeks then switching to rocatinlimab 600 mg Q2W from week 18 through 36. A 20-week off-drug follow-up period ensued thereafter. [EADV 2022, abstract 3587]

At week 16, H&N EASI scores improved significantly with all rocatinlimab doses compared with placebo. For the 300- and 600-mg doses, least-squares mean (LSM) percent changes from baseline ranged between –59 and –65 (vs –17 with placebo; p<0.001 for all comparisons). For the 150-mg dose, LSM percent change was –44, which was still greater than that seen with placebo (p=0.008). These findings align with those observed in the primary analysis.

Week 24 saw deepening of responses. In the placebo-rocatinlimab arm, the week-16 LSM percent change in H&N EASI score jumped to –29. When the other rocatinlimab doses were compared against the placebo-rocatinlimab arm, the LSM changes remained greater, more so with the higher doses (–65, –68, and –78 for 300 mg, 600 mg Q4W, and 600 mg Q2W, respectively; p≤0.001 for all). These responses further deepened by week 36.

“Importantly, rocatinlimab induced long-term responses,” Guttman-Yassky continued, pertaining to the week-56 results. “Of note, after week 36, the patients did not receive the drug anymore [yet] there was maintenance of responses for an additional 20 weeks in a hard-to-treat area like the face.”

In the full analysis set (placebo-controlled phase), the most frequent treatment-emergent adverse events with rocatinlimab were pyrexia, nasopharyngitis, AD worsening, and chills. “Of note, nasopharyngitis and exacerbation of AD were more prevalent in the placebo arm,” said Guttman-Yassky. In the post hoc analysis, no new safety signals were observed. There were no new H&N lesions.

Unique mechanism of action

“This is the first evidence of an anti-OX40 monoclonal antibody improving disease severity in patients with hard-to-treat H&N AD,” said Guttman-Yassky. Although patients were mostly on the severe spectrum, all rocatinlimab doses achieved success in improving H&N EASI scores from baseline, she pointed out.

“[The current findings suggest that rocatinlimab] may be beneficial for H&N AD … and may thus ameliorate H&N lesions in AD without the challenges seen with interleukin 4 inhibitors,” she continued.

“[The] durability of response with rocatinlimab is unique among current AD therapies, potentially reflecting the unique mechanism of action, and may be suggestive of disease modification,” said Guttman-Yassky. “Thus, rocatinlimab represents a potential novel treatment option for [H&N] AD.”