Lebrikizumab ADvocate1 and 2 Monotherapy and ADjoin (Long-Term) Trials: Use of Topicals Therapies.

Atopic dermatitis (AD) is a chronically relapsing, complex skin disease characterized mainly by skin lesions and itch. The first-line treatment for patients with AD includes topical therapy, such as topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI). Long-term use of topical medications can be burdensome for patients, and despite these burdens, topicals remain a frequent treatment option, not only in patients with mild-to-moderate disease, but also as concomitant therapy in patients with moderate-to-severe disease. Lebrikizumab is a novel monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. This review focuses on the use of topical medications in the lebrikizumab ADvocate1&2 monotherapy trials and ADjoin long-term extension study in the context of similar trials for interleukin (IL)-13/IL-4 inhibitors. In the first 16 weeks of the ADvocate1 and ADvocate2 monotherapy clinical trials, topical therapy was not permitted, and patients receiving topicals were considered nonresponders in the primary analysis. In the subsequent 36-week maintenance period, concomitant therapy was permitted at investigator discretion; however, most patients did not use TCS (TCS use: 11.9% and 9.7% for lebrikizumab treatment every 4 weeks [Q4W] and 2 weeks [Q2W], respectively). Likewise, in the ADjoin long-term extension study, concomitant therapy was permitted at investigator's discretion; however, the majority of patients did not use TCS up to 2 years of treatment (TCS use: 12.1% and 8.5% for lebrikizumab Q4W and Q2W in patients from ADvocate1&2, respectively). Treatment with lebrikizumab monotherapy improved clinical signs and symptoms of AD, and demonstrated stable long-lasting disease control with less frequent dosing (Q4W), with no or minimal use of topicals. Topical use across clinical trials for approved monotherapy biologics (dupilumab, lebrikizumab, and tralokinumab) was reported, and topical therapy was permitted in the maintenance period. For nemolizumab, there is no monotherapy data available in AD.