NATIENS: Optimal Management and Mechanisms of SJS/TEN

Inclusion Criteria:

1. Age >18 years

2. Subject and/or legally authorized representative must be able to understand andprovide informed consent.

3. Erythematous to dusky macules that show evidence of coalescing and/or denuding skinor blistering in a predominantly truncal distribution (Nikolsky sign = sloughingwith direct lateral pressure on non-blistered but involved skin should be consideredas a supportive feature

4. At least two of the following:

5. Mucous membrane involvement

6. Prodromal symptoms including fever, myalgia, and headache

7. Evidence of disease progression with an increasing number of skin lesions

8. History of a newly used medication within the last 2 months that has not beentolerated for longer than 12 weeks in the past

9. Females of childbearing potential must have a negative pregnancy test prior torandomization.

Exclusion Criteria:

1. Subject or legally authorized representative is not willing to provide informedconsent.

2. A serious drug reaction or possible alternative dermatologic diagnosis at the timeof initial evaluation not in keeping with drug-induced SJS/TEN (e.g. graft versushost disease).

3. If greater than 5 days has elapsed from onset of initial cutaneous or mucosal signsof the disease as obtained by patient history or documentation.

4. Patients who have received etanercept in the last 6 months.

5. Patients who in time since onset of SJS/TEN illness have received intravenous immuneglobulin (IVIg) or > 2 doses of pulsed corticosteroid (defined by > 250 mgprednisone equivalent) prior to enrollment in the study.

6. End-stage liver disease (Child Pugh A, B or C or severe liver dysfunction).

7. Grade 2 or higher liver dysfunction (alanine aminotransferase >3 fold or bilirubin >3 fold the upper limit of normal).

8. Any organ transplant.

9. Pre-existing Class III/IV Heart Failure (New York Heart Association FunctionalClassification).

10. Multiple Sclerosis or other demyelinating diseases.

11. Pregnancy or breastfeeding.

12. Current or past history of immune checkpoint inhibitor therapy for cancer.

13. Absolute need for a drug that interacts with cyclosporine without an appropriatesubstitution.

14. History of other immunosuppressive or immunomodulatory therapy that couldsignificant impact treatment or interpretation of response to treatment (i.e.azathioprine, methotrexate, mycophenolate mofetil, mycophenolate sodium, rituximab,JAK inhibitors, IL-17 inhibitors, IL-23 inhibitors, other TNF alpha antagonists (seeMOP).

15. Use of surgical debridement and/or xenograft.

16. Known positive SARS-CoV-2 on RT-PCR within 10 days prior to screening or within 5days of admission or symptomatic COVID-19 infection at screening. Symptomaticpatients with a positive SARS-CoV-2 on RT-PCR or comparable assay beyond 10 daysmust be evaluated by the Independent Protocol Monitor.

17. Clinical or radiographic evidence of active tuberculosis or endemic mycoses.

18. History or evidence of any other clinically significant medical or psychiatricdisorder, condition or disease that in the opinion of the treating physician wouldpose a risk or interfere with evaluation or completion of the study such as knownsepsis/systemic infection requiring antibiotic therapy.

19. Known hypersensitivity to Enbrel® (etanercept).

20. Receipt of a live attenuated vaccine within 30 days of enrollment.