What Are The Best, Safest Systemic Therapies for Atopic Dermatitis?

Jonathan I. Silverberg, MD, PhD, MPH

A systematic review and network meta-analysis of systemic atopic dermatitis therapies suggest upadacitinib, abrocitinib, and dupilumab are associated with the best efficacy outcomes among the robust drug class options.

The research, presented at the American Academy of Dermatology (AAD) Virtual Meeting Experience this weekend, provides a unique comparison of systemic agents for key outcomes in moderate to severe atopic dermatitis treatment, including Eczema Area Severity Index (EASI) and Investigator’s Global Assessment (IGA) scores.

Led by Jonathan I. Silverberg, MD, PhD, MPH, of the George Washington University School of Medicine and Health Sciences, investigators conducted a systematic literature review and a network meta-analysis of randomized controlled trials observing systemic therapy in adults and adolescents with atopic dermatitis.

As they noted, head-to-head systemic therapy trials are lacking in atopic dermatitis. They hypothesized a meta-analysis could provide comparative context into the efficacy and safety of such agents and could even inform clinical decisions.

The Pfizer-sponsored assessment observed both monotherapy and combination systemic therapy in published research for atopic dermatitis. Silverberg and colleagues conducted analysis of randomized controlled trials including adult and adolescent patients through October 24, 2019.

Short-term efficacy, defined as 12-16 weeks of systemic therapy for EASI and IGA responses, as well as safety data were analyzed in fixed-effects and random-effects Bayesian network meta-analysis models.

The team found 19 published phase 2 or 3 randomized controlled trials involving abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab, and upadacitinib.

In monotherapy use, once-daily 30 mg upadacitinib was associated with the numerically highest rate of treatment efficacy (51.6% achieving EASI 90), followed by once-daily 200 mg abrocitinib (39.2%), once-daily 15 mg upadacitinib (34.5%), biweekly 200 mg dupilumab (27.6%), and once-daily 100 mg abrocitinib (22.2%).

In combination therapy use, the abrocitinib regimen was associated with a 48.7% rate of EASI 90. Other efficacious combination systemic therapy regimens included dupilumab (41.7%) and once-daily 100 mg abrocitinib (37.9%).

Investigators observed consistent benefits in IGA and patient-reported outcomes with the systemic therapy regimens.

Treatment-emergent adverse events were more common in every active treatment regimen than in placebo, aside for biweekly 300 mg dupilumab (OR, 0.96; 95% CI, 0.45 – 2.18) and once-daily 100 mg abroctinib (OR, 0.95; 95% CI, 0.35 – 2.66), both used in combination therapy for atopic dermatitis.

The investigators concluded the assessment showed favor on efficacy and safety marks to both monotherapy and combination abrocitinib and dupilumab among other atopic dermatitis systemic therapies.

“To conclude, abrocitinib, dupilumab, and upadacitinib were consistently the most effective systemic therapies in adults and adolescents with atopic dermatitis,” Silverberg said. “Abrocitinib and dupilumab combination therapy demonstrated the greatest efficacy, and there was no significant difference in treatment-emergent adverse events in these short-term randomized controlled trials, although there were some numerical increases observed.”

The study, “Comparative Efficacy and Safety of Systemic Therapies Used in Adult and Adolescent Moderate-to-Severe Atopic Dermatitis (AD): A Systematic Literature Review (SLR) and Network Meta-Analysis (NMA),” was presented at AAD VMX.