Lebrikizumab–topical corticosteroid combo improves outcomes in moderate-to-severe AD

Treatment with lebrikizumab, when combined with low- to mid-potency topical corticosteroid (TCS), helps reduce disease severity in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD), with a safety profile consistent with that reported in previous AD studies, according to the phase III ADhere trial.

“Combining a systemic agent such as lebrikizumab with as-needed application of topical therapies mimics clinical practice settings. In this study, all primary and key secondary endpoints were met at week 16,” the investigators said.

Compared with patients treated with placebo plus TCS, those who received lebrikizumab plus TCS more frequently achieved Investigator’s Global Assessment score (IGA) of 0 or 1 (with at least a two-point improvement from baseline; 41.2 percent vs 22.1 percent; p=0.01), as well as a 75-percent improvement in the Eczema Area and Severity Index (EASI-75; 69.5 percent vs 42.2 percent; p<0.001). [JAMA Dermatol 2023;doi:10.1001/jamadermatol.2022.5534]

“The lebrikizumab plus TCS group achieved statistically significant improvements as early as week 8 for IGA (0,1) response and week 4 for EASI-75 response. [This] group also achieved statistically significant improvements vs TCS alone in all key secondary endpoints, including skin clearance, improvement in itch, itch interference on sleep, and enhanced quality of life (QoL),” the investigators pointed out.

“Moderate-to-severe AD is characterized by intense itching, which is associated with impaired QoL, sleep disturbance, anxiety, and depressive symptoms. In this randomized clinical trial, statistically significant improvements in itch and interference of itch on sleep loss were seen as early as week 4 in patients in the lebrikizumab plus TCS group,” they added. [Ann Allergy Asthma Immunol 2018;121:340-347]

According to an international consensus-based framework for the treatment of AD, there is no single outcome assessment tool that can capture the full benefit of treatment. As such, composite endpoints may provide a more comprehensive assessment. The investigators noted that ADhere was able to capture the clinical benefit of lebrikizumab through the combined endpoint of physician-assessed clinical sign of skin clearance (EASI-75) and patient-reported outcome of improvement in itch (Pruritus NRS). [Acta Derm Venereol 2021;101:adv00402]

Mild-to-moderate adverse events

The benefit-to-risk profile of lebrikizumab in ADhere is consistent with that seen in prior lebrikizumab AD studies. The treatment-emergent adverse events (TEAEs) were mostly mild or moderate in severity, nonserious, and did not result in study withdrawal.

The TEAEs frequently reported among patients on lebrikizumab plus TCS included conjunctivitis (4.8 percent), headache (4.8 percent), hypertension (2.8 percent), injection site reactions (2.8 percent), and herpes infection (3.4 percent); the frequency of these TEAES was ≤1.5 percent in the placebo plus TCS group. Patient-reported serious AEs were similar in the two treatment groups (1.4 percent vs 1.5 percent).

ADhere included 211 adult and adolescent (aged ≥12 to <18 years, weighing ≥40 kg) patients across Germany, Poland, Canada, and the US. Their mean age was 37.2 years; 48.8 percent of patients were women, 14.7 percent were Asian, and 13.3 percent patients were Black/African American.

Of the patients, 145 received lebrikizumab and 66 placebo. Lebrikizumab was administered subcutaneously at a loading dose of 500 mg at baseline and week 2, followed by 250 mg every 2 weeks thereafter. Both lebrikizumab and placebo were given in combination with TCS for 16 weeks.

“Taken together, the efficacy and safety data reported herein suggest that lebrikizumab plus TCS may be an effective treatment option for adult and adolescent patients with moderate-to-severe AD,” according to the investigators.

They shared that two ongoing studies will address the long-term efficacy and safety of lebrikizumab (ADjoin) and its effect on vaccine immune responses in adult patients with moderate-to-severe AD (ADopt).