Direct and Indirect Effects of Crisaborole Ointment on Quality of Life in Patients with Atopic Dermatitis: A Mediation Analysis
Eric L. Simpson, Gil Yosipovitch, Andrew G. Bushmakin, Joseph C. Cappelleri, Thomas Luger, Sonja Ständer, Wynnis L. Tom, William C. Ports, Michael A. Zielinski, Anna M. Tallman, Huaming Tan, Robert A. Gerber
Crisaborole ointment is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis. Using pooled data from two phase 3 studies (NCT02118766/NCT02118792), mediation modeling determined the interrelationship among pruritus, quality of life (QoL), and treatment. Patients aged ≥ 2 years received crisaborole ointment 2% or vehicle twice daily for 28 days. QoL measures were Dermatology Life Quality Index (DLQI) (≥ 16 years) and Children’s Dermatology Life Quality Index (CDLQI) (2–15 years). Pruritus was assessed by the Severity of Pruritus Scale (4-point scale from 0 to 3). The indirect effect of crisaborole on QoL mediated through its effect on pruritus was 51% (DLQI model, p < 0.05) and 72% (CDLQI model, p < 0.05). Direct effect (other effects) on QoL was 49% (DLQI model, p < 0.05) and 28% (CDLQI model, p > 0.05). Mediation modeling shows that crisaborole affects QoL mostly indirectly through pruritus severity reduction.
Atopic dermatitis, a skin disease characterized by inflammation and itching, has a significant impact on a patient’s quality of life. Mediation modeling can be used to find if a causal factor influences an outcome factor through a third factor, the mediator. The mediation analysis presented here shows that quality of life in patients with atopic dermatitis is mostly influenced by the effect of the treatment on itching.