Dupilumab (Dupixent®; Sanofi, Paris, France; Regeneron, New York, USA) is a fully human monoclonal antibody, which has shown significant efficacy and a favourable safety profile in moderate-to-severe atopic dermatitis alone and in combination with topical corticosteroids.
The U.S. Food and Drug Administration (FDA) granted Dupixent® Breakthrough Therapy designation in uncontrolled moderate-to-severe atopic dermatitis in 2014.
The Biologics License Application (BLA) for dupilumab was recently accepted for Priority Review by the U.S. FDA with a target action date of March 29, 2017, for the treatment of adult patients with inadequately controlled moderate-to-severe atopic dermatitis. The BLA contains data from three pivotal phase 3 clinical studies evaluating dupilumab as monotherapy and in concomitant administration with topical corticosteroids.
What is dupilumab used for?
- Dupilumab is indicated for the treatment of adult patients with inadequately controlled moderately to severe atopic dermatitis.
- Current treatment options include moisturisers, antihistamines, topical corticosteroids or topical calcineurin inhibitors (TCIs), systemic corticosteroids, systemic calcineurin inhibitors, phototherapy, and other oral immune suppressants.
How does dupilumab work?
- Dupilumab is thought to work by blocking the inflammation that causes atopic dermatitis.
- Atopic dermatitis is characterised by type 2 helper T (Th2) cell-driven inflammation,
- Dupilumab, a fully-human monoclonal antibody, is directed against the shared IL-4 receptor alpha subunit, which blocks signalling from both IL-4 and IL-13.
- IL-4 and IL-13 are key cytokines (signalling molecules that are made by cells and help to control the immune system and fight disease) that are required for the initiation and maintenance of the Th2 (Type 2 helper T-cell) immune response, which is believed to be a critical pathway in allergic inflammation.
Dosage and administration
- Dupilumab is administered as a subcutaneous injection.
What are the adverse effects of dupilumab?
Most common (> 5%) adverse reactions associated with dupilumab treatment in clinical trials were:
- Upper respiratory tract infection
- Injection site reactions
- Allergic conjunctivitis
- Herpes infections
- Atopic dermatitis exacerbation
Dupilumab promising for atopic dermatitis in phase 3 studies
- Dupilumab is a fully human monoclonal antibody that inhibits the actions of both IL-4 and IL-13.
- Clinical trials of systemic dupilumab in moderate-to-severe atopic dermatitis have demonstrated marked improvement in patient symptoms, including pruritus and clinically visible disease.
- Importantly, dupilumab treatment has been correlated with changes in the molecular signature of diseased skin, with reduction of both inflammatory and proliferative markers.