ADvocate 1 and 2: Lebrikizumab efficacy in atopic dermatitis maintained at 1 year

Maintenance lebrikizumab monotherapy appears to improve outcomes in patients with moderate-to-severe atopic dermatitis (AD), according to results of the phase III ADvocate1 and ADvocate2 trials.

“[The] robust efficacy identified at 16 weeks … was maintained in the majority of patients with moderate-to-severe AD treated with lebrikizumab through 52 weeks,” said study author Dr Andrew Blauvelt from the Oregon Medical Research Center, Portland, Oregon, US, at EADV 2022.

Participants in the identical, double-blind ADvocate1 and ADvocate2 trials were adolescents (age ≥12 years; weight ≥40 kg) or adults with moderate-to-severe* AD for ≥1 year. They were randomized 2:1 to receive subcutaneous lebrikizumab (500 mg loading dose at baseline and week 2, followed by lebrikizumab 250 mg Q2W; n=236) or placebo Q2W (n=120). Responders** were re-randomized 2:2:1 at the end of the 16-week induction period to receive lebrikizumab (250 mg Q2W [n=113] or 250 mg Q4W [n=118]) or placebo Q2W (lebrikizumab withdrawal; n=60) for 36 weeks. Topical steroid use was allowed after week 16. Average EASI score at baseline (week 0) was 27–29 and was reduced to 2–3 at week 16.

At week 52, IGA 0 or 1 with a ≥2-point improvement was maintained by a greater proportion of patients in the lebrikizumab Q2W and Q4W arms compared with the lebrikizumab withdrawal arm, both in the ADvocate1 (75.8 percent [Q2W] and 74.2 percent [Q4W] vs 46.5 percent [withdrawal]) and ADvocate2 trials (64.6 percent and 80.6 percent vs 49.8 percent). [EADV 2022, abstract N°: 3456]

At week 52, maintenance of EASI75 was observed in 79.2 and 77.4 percent of lebrikizumab Q2W recipients in ADvocate 1 and 2, respectively, and 79.2 and 84.7 percent of lebrikizumab Q4W recipients in ADvocate 1 and 2, respectively, compared with 61.3 and 72.0 percent of patients in the withdrawal arm in ADvocate 1 and 2, respectively.

Between baseline and week 52, 81.2 and 90.3 percent of patients on lebrikizumab Q2W in ADvocate 1 and 2, respectively, maintained a ≥4-point improvement on the Pruritus Numeric Rating Scale (NRS), as did 80.4 and 88.1 percent, respectively, on lebrikizumab Q4W, compared with 65.4 and 67.6 percent of patients in the lebrikizumab withdrawal arm in ADvocate 1 and 2, respectively.

“The Q2W dosing is very similar to the Q4W dosing and we still have very high responses in the patients randomized to placebo,” commented Blauvelt. “Loss of clinical response following withdrawal of lebrikizumab was slow, with approximately half of patients re-randomized to placebo still showing response at week 52.”

Treatment-emergent adverse events (TEAEs) throughout the 52-week trial period were documented in 58.1 and 67.8 percent of lebrikizumab recipients (any dose) in ADvocate 1 and 2, respectively, and were mostly mild (31.1 and 27.5 percent, respectively) or moderate (22.8 and 35.9 percent, respectively) in severity. Serious AEs occurred in 3.3 and 2.7 percent, respectively. AEs led to treatment discontinuation in 2.3 and 3.9 percent, respectively. There was one death in the ADvocate 2 trial which was deemed unrelated to the study drug.

The most common TEAEs (≥5 percent) in lebrikizumab recipients in the ADvocate 1 and 2 trials were AD (7.8 and 10.1 percent, respectively), nasopharyngitis (6.8 and 9.6 percent), and conjunctivitis (8.3 and 8.1 percent). The most common TEAEs of special interest were conjunctivitis cluster (13.5 and 14.7 percent), herpes infection (5.0 and 4.9 percent), and skin infections (3.0 and 4.9 percent).

The use of rescue medication was documented in 14 and 16.4 percent of patients in ADvocate 1 and 2, respectively. “Only about 15 percent of all patients in the maintenance period were using topical steroids. The majority of the responses … we believe were due to the drug effect of lebrikizumab and not due to concomitant topical steroids,” said Blauvelt.

“[The results suggest that] specific targeting of IL-13 with lebrikizumab Q2W or Q4W in maintenance is highly efficacious in adolescents and adults, with a safety profile similar to previous studies,” he concluded.