麻豆传媒

Lebrikizumab, an investigational interleukin (IL)-13 inhibitor seeking to join an increasingly crowded market for atopic dermatitis treatments, effectively reduced symptoms of the condition (a.k.a. eczema) when combined with topical corticosteroids, researchers reported.

In a randomized trial -- one of three phase III studies that developers Eli Lilly and Almirall have completed for the product -- 41.2% of patients receiving the active drug achieved Investigator's Global Assessment (IGA) scores of 0 or 1 by week 16, compared with 22.1% of those assigned to placebo injections plus topical steroids (P=0.01), according to Eric L. Simpson, MD, of Oregon Health & Science University in Portland, and colleagues.

As well, reductions of 75% in symptoms as assessed with the Eczema Area and Severity Index (EASI-75) were achieved by 69.5% of the lebrikizumab-steroids group versus 42.2% of the placebo-steroids group (P<0.001), the researchers . Participants in the trial included adolescents as young as 12 as well as adults.

The results from ADhere follow equally glowing findings reported in early 2022 for the other two pivotal studies, ADvocate-1 and ADvocate-2. Almirall and Lilly have submitted marketing applications in and , respectively.

As Simpson and colleagues explained, topical steroids remain the principal treatment for atopic dermatitis, although targeted drugs including biologic agents and Janus-associated kinase inhibitors have won approvals in recent years for moderate-to-severe cases. However, the group wrote, "[d]ue to the heterogeneity of [atopic dermatitis], there remains a need to provide additional therapeutic options for long-term management."

By inhibiting IL-13, lebrikizumab blocks formation of a complex with IL-4 that then prompts release of inflammatory cytokines. This is the same mechanism as with tralokinumab (Adbry), approved in December 2021 for moderate-to-severe atopic dermatitis. The ultimate effect is also similar to that of dupilumab (Dupixent), another approved drug for the condition, except that dupilumab acts on the IL-4 side of the equation.

The point of the current study, Simpson and colleagues explained, was to examine the drug in combination with topical steroids, which may better reflect how such therapies will be used in ordinary practice. In other inflammatory diseases such as rheumatoid arthritis, targeted therapies are nearly always given along with conventional agents.

ADhere randomized 211 patients 2:1 to the active-drug combination or to placebo plus steroids. Participants' mean age was about 37; just over 20% were younger than 18. Half the sample were male and about 61% were white. Study sites were located in the U.S. (accounting for 72% of all participants), Canada, Germany, and Poland.

EASI scores at baseline averaged about 27. To be eligible, participants had to have IGA scores of 3 or 4. Some 70% of participants were at level 3.

Lebrikizumab was administered every 2 weeks at 500 mg for the first two doses and 250 mg thereafter for 16 weeks. Triamcinolone acetonide 0.1% and hydrocortisone 1% creams were the topical steroids used.

Superior results were seen for lebrikizumab by the 8th week of treatment. At that point, nearly 60% of that group had achieved EASI-75, compared with about 25% of the placebo arm. Following week 8, response rates continued to increase in both groups to a similar degree. The same pattern was seen for other response types, such as EASI-90 (90% symptom improvement) and pruritus scores.

Simpson and colleagues noted that response rates were higher for some outcomes than were seen in the ADvocate monotherapy trials (in which EASI-75 was reached by 52-59% of patients, for example), presumably reflecting the steroids' added contribution.

Treatment-emergent adverse events were more common with lebrikizumab at rates of 43.4% versus 34.8%. Conjunctivitis (seven cases vs none) and infection (24 vs 9) accounted for much of the difference. Four patients receiving lebrikizumab and one in the placebo group developed injection-site reactions. These were "consistent with past studies," the investigators wrote.

The chief limitation was the 16-week duration, Simpson and colleagues indicated, which meant the study had nothing to say about long-term safety or durability of efficacy. A 2-year extension is now underway with participants choosing to continue.

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