Patients with moderate-to-severe atopic dermatitis who responded to lebrikizumab after 16 weeks of treatment largely kept their gains over three years of continuous therapy, according to a post hoc analysis published in Dermatology and Therapy. After 152 weeks of continuous treatment, 88.6% of week 16 responders on the every-4-weeks regimen and 80.0% on the every-2-weeks regimen maintained an EASI 90 response, meaning at least 90% improvement from baseline in Eczema Area and Severity Index. Complete skin clearance, defined as EASI 100, was maintained by 64.3% of Q4W patients and 68.8% of Q2W patients who had achieved it at week 16.
The analysis pooled data from the identically designed phase 3 trials ADvocate1 and ADvocate2, which tested lebrikizumab monotherapy in adults and adolescents with moderate-to-severe atopic dermatitis. Responders at week 16, defined as patients achieving either an EASI 75 response or an Investigator’s Global Assessment score of 0 or 1 with at least a 2-point improvement, without rescue medication, were re-randomized to lebrikizumab every 2 weeks, every 4 weeks, or placebo withdrawal for a 36-week maintenance period. Those who completed the parent studies could enroll in the ADjoin extension study, where they continued the same maintenance regimen for an additional 100 weeks. The withdrawal arm was excluded from this analysis because those patients did not receive continuous treatment.
In total, 291 week 16 responders were re-randomized, with 118 assigned to lebrikizumab Q4W, 113 to Q2W, and 60 to placebo. Of these, 99 patients in the Q4W arm and 82 in the Q2W arm entered ADjoin. Mean patient age was about 35 years in both groups, and mean duration since atopic dermatitis onset exceeded 22 years, reflecting a long-standing chronic disease population. The analysis population was the pooled modified maintenance primary population receiving continuous lebrikizumab through all three studies.
Stability was assessed at the individual patient level, defined as maintaining a given response at at least 80% of attended study visits between week 16 and week 152, with 100% representing no fluctuations. By this measure, 92.9% of Q4W patients and 92.7% of Q2W patients maintained a stable EASI 75 response over the full three years. Stability at the EASI 90 threshold reached 77.8% with Q4W and 81.1% with Q2W, while stable EASI 100 responses were maintained by 57.9% and 63.6% of week 16 EASI 100 responders, respectively. A stable absolute EASI score of 7 or less was preserved by 96.8% of Q4W and 97.3% of Q2W patients, and the stricter EASI of 1 or less was maintained stably by 70.3% and 73.7%.
Itch outcomes followed a similar course, although the instruments changed over time. Of week 16 Pruritus Numeric Rating Scale responders with scores of 0 or 1 followed through week 104, 84.0% of Q4W and 84.2% of Q2W patients maintained that near-complete itch resolution at week 104, and stable Pruritus NRS (0, 1) responses were maintained by 70.3% and 69.0% of responders. Stable minimal-to-no sleep loss was maintained through week 104 by 91.7% of Q4W and 97.0% of Q2W patients. Because daily diary collection for the Pruritus NRS halted after two years, the POEM itch category was used to assess itch through week 152, where POEM itch (0, 1) responses rose from 39.3% to 69.1% among Q4W patients and from 35.9% to 66.0% among Q2W patients between week 16 and week 152.
Notably, several measures of response depth actually deepened over time rather than eroding. Among week 16 IGA (0, 1) responders, the proportion achieving complete clearance, an IGA score of 0, rose from 29.9% to 50.0% in the Q4W arm and from 33.8% to 63.4% in the Q2W arm by week 152. An absolute EASI score of 1 or less was reached at week 152 by 72.1% of Q4W and 57.1% of Q2W week 16 EASI 75 responders. POEM total scores of 0 or 1, indicating near-total symptom resolution by patient report, climbed from 11.0% at week 16 to 32.7% and 24.0% at week 152 in the Q4W and Q2W arms, respectively.
Flare burden was examined using three hierarchical definitions: any rescue medication use, including low-potency topical corticosteroids, topical calcineurin inhibitors, or crisaborole; use of high-potency topical corticosteroids or systemic rescue medication; and adverse events due to worsening atopic dermatitis captured as treatment-emergent adverse events. Among stable EASI 75 responders on the Q4W regimen, 72.8% experienced no flare at all under the broadest definition through 152 weeks, with 81.5% flare-free under the high-potency or systemic definition and 92.4% flare-free under the adverse-event definition. The corresponding incidence rate was 0.19 flares per patient-year for any rescue use, roughly one flare every five patient-years, 0.12 for high-potency or systemic rescue, and 0.04 for adverse events due to worsening disease. Rates were lower among stable EASI 90 responders, with an incidence rate of 0.08 flares per patient-year under the broadest definition.
The authors note that the absence of a universally accepted flare definition in atopic dermatitis complicates interpretation, and that their deliberately conservative approach, counting even low-potency topical rescue use as a flare, may overestimate flare rates relative to definitions requiring clinically meaningful worsening. They also compared their findings with other advanced therapies, observing that dupilumab long-term extension data showed sustained aggregate efficacy through three years but without comparable individual-trajectory stability or flare incidence reporting, and that tralokinumab extension data showed approximately 84% of patients maintaining EASI 75 through two years. In a stability analysis subsequently replicated for tralokinumab using the same definition, lebrikizumab Q4W achieved a stable EASI of 7 or less in 96.8% of patients, while tralokinumab reached 71.4% in a population enrolled irrespective of parent-trial response, a difference the authors caution is limited by cross-trial comparability.
Several limitations temper the findings. All statistics are descriptive because this was a post hoc analysis using observed data without imputation, and ADjoin included no placebo or active comparator arm. The analysis was restricted to week 16 responders, excluding patients who did not meet response criteria, some of whom might have improved with longer treatment. Attrition over the extended follow-up, with 68 of 99 Q4W and 63 of 82 Q2W patients contributing nonmissing data at week 152, may affect generalizability, and the switch from Pruritus NRS to POEM itch after week 104 limits comparability of itch outcomes across the full period. Subgroup analyses involved small patient numbers and should be interpreted cautiously. The flare analysis was intentionally limited to the Q4W arm.
Lebrikizumab is a monoclonal antibody that binds interleukin-13 with high affinity and a slow dissociation rate, blocking a cytokine recognized as a central driver of atopic dermatitis inflammation. The authors conclude that continuous lebrikizumab treatment through three years provided stable disease control in skin and itch symptoms with infrequent flares among week 16 responders, and they suggest these data support confidence in less frequent maintenance dosing, including the FDA-approved every-8-weeks regimen, which may reduce treatment burden. They call for future studies in broader patient populations and real-world settings to further establish the drug’s place in atopic dermatitis management.
Subject of Research: Long-term stability and depth of response with lebrikizumab in moderate-to-severe atopic dermatitis
Article Title: Lebrikizumab Provides Stable and Deep Long-Term Response with No/Minimal Fluctuations up to 3 Years in Patients with Moderate-to-Severe Atopic Dermatitis
Article References: Gold, L. S., Wollenberg, A., Lio, P., Carrascosa, J. M., Del Rosso, J., Igawa, K., Hong, H. C.-H., Merola, J., Kircik, L., Gallo, G., Ding, Y., Yang, C., Wolf, E., Agell, H., & Vestergaard, C. (2026). Lebrikizumab Provides Stable and Deep Long-Term Response with No/Minimal Fluctuations up to 3 Years in Patients with Moderate-to-Severe Atopic Dermatitis. Dermatology and Therapy. https://doi.org/10.1007/s13555-026-01962-0
Image Credits: AI Generated
DOI: 10.1007/s13555-026-01962-0
Keywords: atopic dermatitis, lebrikizumab, EASI 90, EASI 100, skin clearance, itch, ADvocate trials, ADjoin extension, flare rates, interleukin-13, biologic therapy, long-term extension
News Source: Ophelia Keating. (October 28, 2026). Three Years of Lebrikizumab Kept Atopic Dermatitis Controlled in Long-Term Extension Analysis. Scienmag.
