Dupilumab (DPL) for treatment of bullous pemphigoid (BP): Liberty-bp adept trial results

Summary: BP is a potentially life-threatening, relapsing, autoimmune blistering skin disease. DPL, by blocking the shared receptor component for interleukin-4/13, targets underlying type 2 inflammatory drivers of BP pathogenesis. LIBERTY-BP ADEPT (NCT04206553), a randomized, double-blind, placebo (PBO)-controlled, 52-week (W) study evaluated DPL in moderate–severe BP patients. All patients started standard oral corticosteroids (OCS) on Day 1; OCS were tapered if BP was controlled. The primary endpoint, proportion of patients achieving sustained remission at W36, required complete remission and off OCS no later than W16, no relapse off OCS, and no rescue use through W36. Among 106 adult patients (DPL 300 mg Q2W/PBO, n=53/53), baseline characteristics were balanced (mean age, 71.3 years). At W36, 20.2% vs 4.0% of DPL vs PBO-treated patients achieved sustained remission (P=0.0114). More DPL-treated patients achieved ≥90% improvement in BP Disease Area Index activity score (40.5% vs 9.8%; P=0.0003) and ≥4-point reduction in Peak Pruritus Numerical Rating Scale score (39.8% vs 10.6%; P=0.0006). DPL patients had 1678 mg less mean cumulative OCS exposure over 36 weeks (P=0.0220) and 54% lower risk of rescue use (P=0.0016) vs PBO. Quality-of-life improvements favored DPL (nominal P=0.0463). Overall, 96.2% of patients reported treatment-emergent adverse events (TEAEs) with higher TE-serious AEs in PBO (30.2%) than DPL (22.6%). DPL showed significant benefits across multiple aspects of BP including sustained remission, reduced disease activity, itch, and OCS and rescue medication use. Overall safety was consistent with the known DPL safety profile. The first four authors are senior authors. Victoria Werth¹, Frederic Caux², Dédée Murrell³, Pascal Joly⁴, Margitta Worm⁵, Jennifer Maloney⁶, Lacey Robinson⁷, Nikhil Amin⁶, Joseph Chiarappa⁶, Ariane Dubost-Brama⁸, Deepti Deshpande⁶ 1. University of Pennsylvania, Philadelphia, PA, United States. 2. Avicenne University Hospital, Bobigny, France. 3. University of New South Wales, Sydney, NSW, Australia. 4. Normandy University, Rouen, France. 5. Charité-Universitätsmedizin Berlin, Berlin, Germany. 6. Regeneron Pharmaceuticals Inc.,, Tarrytown, NY, United States. 7. Sanofi, Cambridge, MA, United States. 8. Sanofi, Gentilly, France. Clinical Research: Interventional Research