Systemic immunomodulating therapies for epidermal necrolysis (Stevens‐Johnson syndrome/toxic epidermal necrolysis): A systematic review and meta‐analysis

Summary Background and Objectives Epidermal necrolysis is a rare but severe cutaneous reaction with high mortality. Limited evidence exists regarding the efficacy of systemic immunomodulatory therapies (SITs). Our systematic review aimed to compare SITs with supportive care or one another. Patients and Methods Randomized controlled trials and controlled observational studies (≥ 5 patients of all ages per arm) using the international consensus classification for EN (Bastuji‐Garin, 1993) with no significant baseline differences were included. We searched MEDLINE, Embase, and Cochrane CENTRAL (January 1, 1993–January 22, 2024). Two reviewers independently extracted study and outcome data. A random‐effects meta‐analysis was performed. Results The main outcome was mortality. Secondary outcomes included hospital stay duration, time to complete reepithelialization, complications, and sequelae. 43 studies with 58 treatment comparisons were analyzed. Cyclosporine was superior to IVIG regarding mortality (RR 0.18, 95% CI 0.05–0.58), and corticosteroids plus IVIG reduced serious complications compared to corticosteroids alone (sepsis, RR 0.77, 95% CI 0.31–0.77). Compared to supportive care, only etanercept showed a significant mortality benefit (RR 0.32, 95% CI 0.11–0.93; GRADE: imprecision/unclear clinical importance). Conclusions There is no clear evidence of the superiority of SITs over supportive care, which remains the primary treatment for EN.