A Systematic Review of Efficacy and Safety of Monotherapy and Combination Therapy With Biologic for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Abstract

Background Biologic drugs have the potential to halt the progression of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by decreasing concentrations of tumor necrosis factor-α, a cytokine implicated in epithelial cell death. The objective of this systematic review is to investigate the efficacy and safety of biologic monotherapy and combination therapy for SJS/TEN. Methods MEDLINE and EMBASE in OVID were searched on October 28, 2020. Inclusion criteria were original studies containing human participants diagnosed with SJS/TEN and treated with biologics. Studies were excluded if they were literature reviews, systematic reviews, letters to the editor, or conference abstracts. Results The 38 articles reviewed included 27 (71.1%) case reports, 6 (15.8%) case series, 3 (7.9%) retrospective reviews, and 2 (5.3%) RCTs. The age range of the included studies was 2 to 85 years, the mean age was 46.4 years. The mean body surface (BSA) across the 38 included articles was 31.0%. The average actual mortality reported within the 38 included articles was 9.2%. Both biologic monotherapy and combination therapy were associated with improved outcomes in SJS/TEN. Furthermore, anti TNF-alpha therapy, specifically etanercept, showed improved outcomes as monotherapy. Conclusions Overall, reviewed studies presented a strong case for biologic treatment, both monotherapy and combination use, in SJS/TEN treatment. Based on the number of fatal adverse events observed, biologic monotherapy may be safer compared to combination therapy. Further research with a larger sample size and a randomized control trial design is required.

Tumor necrosis factor-α inhibitor for successful treatment of toxic epidermal necrolysis with severe infection: a case series

“…TNF-a inhibitors have been shown to be safe and to effectively improve signs and symptoms, 5,15,20,21 and they are recommended early in the course of TEN in China. 12 However, clinical experience with TNF-a inhibitors for TEN in the presence of serious active infections is limited because severe infection is a contraindication for TNF-a inhibitor in many cases.…”

A Review of the Systemic Treatment of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis

“…The search parameters included the terms “toxic epidermal necrolysis” or “Stevens-Johnsons syndrome” combined with “systematic review” or “meta-analysis”. A total of 13 relevant studies were included and summarized in Table 1 [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ].…”

“…Several meta-analyses have also found that etanercept and infliximab reduced mortality [ 22 , 23 , 27 ]. A systematic review by Sachdeva et al [ 25 ] also recommended monotherapy with TNF-α inhibitors, especially etanercept, based on the results of the above-mentioned trial [ 96 ]. However, some other meta-analyses did not find beneficial effects of biologic anti-TNF-α for SJS/TEN [ 24 , 26 , 28 ], and the major concern was that most of the published studies were case reports and case series.…”

“…Few case reports have described the use of combination therapy with anti-TNF-α and corticosteroids [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ]. In 2021, Sachdeva conducted a systematic review of 38 studies (including 27 case reports) and found that both biologic monotherapy and combination therapy were associated with improved outcomes in SJS/TEN [ 25 ]. In 2022, Ao et al recruited 25 patients with SJS/TEN and found that combination therapy with etanercept and corticosteroids significantly shortened the duration of acute phase, hospital stay, and skin re-epithelialization in comparison to a corticosteroid monotherapy group.…”

The role of tumor necrosis factor-alpha (TNF-α) inhibitor in steven johnson syndrome/toxic epidermal necrolysis (SJS/TEN) management: a systematic review

“…Our finding is similar to other systematic reviews such as Zhang et al and Sachdeva et al, which found an overall positive effect of TNF-α inhibitors with minimal complications and side effects. 21,22 The limitation of our systematic review is that we mostly included case reports; only three non-case reports were involved in the analysis due to the limited year of publication we used as inclusion criteria. Due to the limited RCT involved in this study, the efficacy and safety of TNF-α inhibitors for SJS/ TEN management cannot be conclusively determined.…”