Original article
Treating toxic epidermal necrolysis with systemic immunomodulating therapies: A systematic review and network meta-analysis

https://doi.org/10.1016/j.jaad.2020.08.122Get rights and content

Background

Various systemic immunomodulating therapies have been used to treat toxic epidermal necrolysis (TEN), but their efficacy remains unclear.

Objective

To perform a systematic review and network meta-analysis (NMA) evaluating the effects of systemic immunomodulating therapies on mortality for Stevens-Johnson syndrome (SJS)/TEN overlap and TEN.

Methods

A literature search was performed in online databases (from inception to October 31, 2019). Outcomes were mortality rates and Score of Toxic Epidermal Necrolysis (SCORTEN)–based standardized mortality ratio (SMR). A frequentist random-effects model was adopted.

Results

Sixty-seven studies involving 2079 patients were included. An NMA of 10 treatments showed that none was superior to supportive care in reducing mortality rates and that thalidomide was associated with a significantly higher mortality rate (odds ratio, 11.67; 95% confidence interval [CI], 1.42-95.96). For SMR, an NMA of 11 treatment arms showed that corticosteroids and intravenous immunoglobulin combination therapy was the only treatment with significant survival benefits (SMR, 0.53; 95% CI, 0.31-0.93).

Limitations

Heterogeneity and a paucity of eligible randomized controlled trials.

Conclusions

Combination therapy with corticosteroids and IVIg may reduce mortality risks in patients with SJS/TEN overlap and TEN. Cyclosporine and etanercept are promising therapies, but more studies are required to provide clearer evidence.

Section snippets

Methods

This NMA was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension guidelines (Supplemental Table I; available via Mendeley at https://doi.org/10.17632/4b3cd3d53x.1).14

Search results and trial characteristics

Sixty-seven studies involving 2079 patients with SJS/TEN overlap and TEN met the inclusion criteria (Supplemental Fig 1; available via Mendeley at https://doi.org/10.17632/4b3cd3d53x.1). A summary of the trial characteristics is presented in Supplemental Table II, A and B (available via Mendeley at https://doi.org/10.17632/4b3cd3d53x.1). Two of the 67 studies showed partially duplicated data; therefore, only 66 studies were included for NMA. Most of the included studies were retrospective

Discussion

This NMA showed that none of the included SITs reduced MRs in patients with SJS/TEN overlap and TEN. However, in the analysis based on SMR, combination therapy with corticosteroids and IVIg significantly reduced the observed mortality risks. Because the range of predicted mortality of patients with SJS, SJS/TEN overlap, and TEN is extremely wide (from 3.2% to 90%), analysis using SMR can account for the baseline severity of the disease, thus reflecting a more accurate treatment response.

Conclusions

In conclusion, this NMA showed that combination therapy with corticosteroids and IVIg may lower mortality risks in patients with SJS/TEN and TEN. Some other treatments (cyclosporine, cyclosporine combined with IVIg, IVIg combined with plasmapheresis, and ETN) are potential effective treatment options but require more evidence. Further studies, such as RCTs, are required to fill the gap in scientific evidence in treating this life-threatening adverse drug reaction.

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  • Cited by (0)

    Drs Tu and Huang contributed equally to this article.

    Funding sources: None.

    Conflicts of interest: None disclosed.

    IRB approval status: Not applicable.

    Reprints not available from the authors.

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