Induction and maintenance phase results
At the end of the 16-week induction period, a greater proportion of patients who had been treated with lebrikizumab than placebo met a primary outcome of IGA 0/1 in each trial (43.1% vs. 12.7% in ADvocate1 and 33.2% vs. 10.8% in ADvocate2).
A similar result was seen for another primary outcome, EASI 75 (58.8% vs. 16.2% and 52.1% vs. 18.1%) and for a secondary outcome, improvement in pruritus using a numerical rating scale (45.9% vs. 13.0% and 39.8% vs. 11.5%).
In the maintenance phase, with respect to responders, Dr. Blauvelt reported “very similar results” between the QW2 and Q4W maintenance dosing, “and still a quite high response in [half] the patients who were randomized to placebo at week 16.”
In the ADvocate1 and ADvocate2 trials, respectively, an IGA 0/1 with at least a 2-point improvement was maintained at week 52 in 75.8% and 64.6% of patients treated with the Q2W lebrikizumab dose, 74.2% and 80.6% of those treated with the Q4W dose, and 46.5% and 49.8% of those given placebo.
EASI 75 was maintained at week 52 in a respective 79.2% and 77.4% of patients treated with the Q2W dose, 79.2% and 84.7% with the Q4W dose, and 61.3% and 72.0% with placebo.
As for maintenance of at least a 4-point improvement in pruritus score, results at 52 weeks were 81.2% and 90.3% for the 2-week dose, 80.4% and 88.1% for the 4-week dose, and 65.4% and 67.6% for placebo.
Although topical corticosteroid treatment was allowed during the maintenance phase, only about 15% of patients needed this, Dr. Blauvelt said.
Different dosing results questioned
During the discussion period, one delegate highlighted that the twice-weekly maintenance dosing schedule seemed to “do worse a little bit” than the 4-week dosing, with both “close to placebo,” although “the long-term effect is already very impressive.”
Dr. Blauvelt noted that a pooled analysis had been done and that “it’s very clear that being on lebrikizumab works better than not being on lebrikizumab.
“Now, Q2W versus Q4W. We believe that this may be due to the long half-life of the drug possibly. It could be due to the slow disassociation rate, it’s binding tightly,” he suggested.
“We also could talk about disease modification, right. So, it opens up the concept of hit hard, hit early for 16 weeks, and then maybe you can modify disease over time,” Dr. Blauvelt said.
He added: “That’s highly speculative, of course.”
Short-term safety data
The 52-week safety profile of lebrikizumab is consistent with previously published data at 16 weeks, Dr. Blauvelt said. The most common adverse events during the studies included atopic dermatitis, nasopharyngitis, conjunctivitis, conjunctivitis allergic, headache, and COVID-19.
“This drug has comparable efficacy with dupilumab and tralokinumab,” said Jashin J. Wu, MD, from the Dermatology Research and Education Foundation in Irvine, Calif., in an interview. He was not involved in the study.
“As it does not have any significant advantages with less long-term safety data, I do not see a place for it in my practice,” Dr. Wu said.
Dupilumab (Dupixent) and tralokinumab (Adbry) are monoclonal antibodies that also block IL-13. Both are already licensed for treating atopic dermatitis. Dupilumab was approved by the Food and Drug Administration in 2017, and tralokinumab was approved in 2021.
The study was funded by Dermira, a wholly owned subsidiary of Eli Lilly. Eli Lilly has exclusive rights for the development and commercialization of lebrikizumab in the United States and all countries outside Europe; European rights belong to Almirall for all dermatology indications, including atopic dermatitis. Dr. Blauvelt acts as an investigator and adviser to these companies as well as many other pharmaceutical companies that are involved in developing new dermatologic treatments. Dr. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.
A version of this article first appeared on Medscape.com.