IL-13 inhibition with lebrikizumab shows high maintenance rates in AD

Up to 80.6% of the ADvocate 1 and 2 trial responders on lebrikizumab maintained clear or almost clear skin in the extension phase from weeks 16 to 52. Interestingly, dosing regimens of every 2 (Q2W) and every 4 weeks (Q4W) did not differ greatly in efficacy.

“Lebrikizumab is a specific IL-13 blocker, it does not interfere with IL-4, and we know now that IL-13 is a critical cytokine in AD pathogenesis,” Prof. Andrew Blauvelt (Oregon Medical Research Center, OR, USA) announced [1]. The phase 3 ADvocate 1 and 2 trials (NCT04146363, NCT04178967) investigated monotherapy with lebrikizumab versus placebo in patients with moderate-to-severe AD. The study investigated patients who responded in the initial 16 weeks and over the course of 52 weeks. Responders were adolescents (≥12 years) and adults (≥18 years), who reached an Eczema Area and Severity Index (EASI)-75 or an Investigator's Global Assessment (IGA) 0/1, which means clear or almost clear skin at week 16 of the trials.

At week 16, 43.1% and 33.2% of study drug participants achieved an IGA 0/1 and 58.8% and 52.1% an EASI-75 improvement in both trials [1,2]. The responders were then re-randomised to 3 different study arms: continue 250 mg of lebrikizumab Q2W, change to Q4W dosing, or placebo Q2W [1]. At baseline, the average age ranged from 33 to 37.5 years, 45.2% to 65.6% of participants were women, and the mean EASI-75 varied between 2.0 and 2.9.

The results of ADvocate 1 and 2 at week 52 showed 75.8% and 64.6% maintaining IGA 0/1 on the Q2W lebrikizumab regimen in comparison with 74.2% and 80.6% in the Q4W arms. Furthermore, a substantial rate of participants in the placebo arms continued to have IGA 0/1: 46.5% and 49.8%. “If we look now at EASI-75, we see very similar results, the Q2W dosing is very similar to the Q4W dosing and we still have very high responses in the participants randomised to placebo,” Prof. Blauvelt elaborated.  The same was true for the maintenance of pruritus improvements.

As for safety results from weeks 0‒52 in Advocate 1 and 2, treatment-emergent adverse events were mostly mild (31.1% and 27.5%) and moderate (22.8% and 35.9%). “The highlight here is the 8.3% and 8.1% conjunctivitis in these studies, something we would expect with the mechanism of action, but at levels that I think are quite reasonable,” Prof. Blauvelt commented. Collectively, the conjunctivitis cluster was 13.5% and 14.7% through week 52, but according to Prof. Blauvelt, the actual rate went down from week 16 to 52.

“The ADvocate studies showed that specific targeting of IL-13 with lebrikizumab either Q2W or Q4W has high maintenance of efficacy and is reasonably tolerated and safe in adolescents and adults with AD,” he concluded.

1. Blauvelt A. Efficacy and safety of lebrikizumab in moderate-to-severe atopic Dermatitis: 52-week results of two randomised, double-blinded, placebo-controlled phase 3 trials (ADvocate1 and ADvocate2). 3D, EADV Congress 2022, Milan, Italy, 7–10. September.
2. Silverberg JI, et al. S026, AAD 2022 Annual Meeting, 25–29 March, Boston, MA, USA.

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Posted on 5 November 202222 February 2024