Evaluation of Combination Therapy With Etanercept and Systemic Corticosteroids for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Multicenter Observational Study

Abstract

Background: Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) are fatal severe cutaneous adverse reactions, without consensus on the medical treatment. The use of systemic corticosteroids or intravenous immunoglobulin (IVIG) remains debatable. Tumor necrosis factor-alpha inhibitors are potentially effective.

Objective: To evaluate the effectiveness and safety of combination therapy using etanercept combined with corticosteroids or IVIG combined with corticosteroids versus corticosteroid monotherapy for patients with SJS-TEN.

Methods: We retrospectively enrolled SJS-TEN patients from Taiwan and the Chinese mainland, during 2014 to 2019. Patients enrolled were treated with corticosteroid monotherapy, or combinations with IVIG or etanercept. We analyzed the clinical characteristics, skin healing time, mortality, and adverse events among these treatment groups.

Results: Among the 242 patients (187 with SJS or SJS-TEN overlapping and 55 with TEN), patients who received combination therapy with etanercept and corticosteroids had lower actual mortality than those with corticosteroid monotherapy and those with IVIG combined with corticosteroids, respectively (0% vs 6.63% and 4.76%). There was a tendency of reducing standardized (observed/predicted) mortality rate (SMR) based on the Score of Toxic Epidermal Necrolysis in etanercept combined with corticosteroids compared with corticosteroid monotherapy and IVIG combined with corticosteroids therapy (SMR [95% CI] 0 [1.80-3.59], 0.71 [0.83-2.64], 0.30 [0.68-6.22]; P = .006). Etanercept combined with corticosteroids showed a reduced skin healing time (12.0 [8.5-14.0], median days [interquartile range]), compared with corticosteroid monotherapy (13.0 [10.0-18.0]) and IVIG combined with corticosteroids therapy (13.5 [10.0-19.5]); P = .004 and P = .012, respectively). Etanercept combined with corticosteroids also showed a lower incidence of adverse event with gastrointestinal hemorrhage than corticosteroid monotherapy, especially in patients with TEN (P = .001).

Conclusions: The tumor necrosis factor-alpha inhibitors and corticosteroids combination therapy was effective and safer than corticosteroid monotherapy for SJS-TEN, and may be considered as an alternative therapy for SJS-TEN patients who responded poorly to conventional corticosteroid therapy.

Keywords: Anti–TNF-α; Combination therapy; Corticosteroid; Etanercept; Intravenous immunoglobulin; Stevens-Johnson syndrome; Toxic epidermal necrolysis.