Evaluation of TNF-α Blockade Effect in Patients With Severe Cutaneous Adverse Drug Reactions
Summary
Severe skin adverse drug reactions can result in death. Toxic epidermal necrolysis (TEN) has the highest mortality (30-35%); Stevens-Johnson syndrome and transitional forms correspond to the same syndrome, but with less extensive skin detachment and a lower mortality (5-15%). Hypersensitivity syndrome, sometimes called Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), has a mortality rate evaluated at about 10%. The aims of this project are (1) to compare the effect of treatment between systemic steroid and anti-TNF-α. Including skin healing time, beginning of re-epithelialization time, internal organ recovery time, mortality rate, adverse events and (2) to investigate the molecular mechanism of severe cutaneous adverse reaction after anti-TNF-α treatment.
Timeline
- Start
- 2009-01
- Primary completion
- 2015-05
- Completion
- 2015-05
Outcome
Mixed primary results
registry Anti- TNF-a Treatment (SJS/TEN) vs Control Group (SJS/TEN); p = 0.01; Kaplan-Meier analysis NCT01276314 ↗
registry Anti- TNF-a Treatment (DRESS) vs Control Group (DRESS); p = 0.06; Kaplan-Meier analysis NCT01276314 ↗
Publications
- Background Paquet P, Paquet F, Al Saleh W, Reper P, Vanderkelen A, Pierard GE. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. Am J Dermatopathol. 2000 Oct;22(5):413-7. doi: 10.1097/00000372-200010000-00005.
- Results Schneck J, Fagot JP, Sekula P, Sassolas B, Roujeau JC, Mockenhaupt M. Effects of treatments on the mortality of Stevens-Johnson syndrome and toxic epidermal necrolysis: A retrospective study on patients included in the prospective EuroSCAR Study. J Am Acad Dermatol. 2008 Jan;58(1):33-40. doi: 10.1016/j.jaad.2007.08.039. Epub 2007 Oct 4.
- Results Paradisi A, Abeni D, Bergamo F, Ricci F, Didona D, Didona B. Etanercept therapy for toxic epidermal necrolysis. J Am Acad Dermatol. 2014 Aug;71(2):278-83. doi: 10.1016/j.jaad.2014.04.044. Epub 2014 Jun 11.
- Wang CW, Yang LY, Chen CB, Ho HC, Hung SI, Yang CH, Chang CJ, Su SC, Hui RC, Chin SW, Huang LF, Lin YY, Chang WY, Fan WL, Yang CY, Ho JC, Chang YC, Lu CW, Chung WH; the Taiwan Severe Cutaneous Adverse Reaction (TSCAR) Consortium. Randomized, controlled trial of TNF-alpha antagonist in CTL-mediated severe cutaneous adverse reactions. J Clin Invest. 2018 Mar 1;128(3):985-996. doi: 10.1172/JCI93349. Epub 2018 Feb 5.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Etanercept | Protein / enzyme biologic | 25 mg | Intravenous |
| Comparator | Prednisolone | Other / unclassified | 1 mg/kg | Intravenous |
| Comparator | Prednisolone | Other / unclassified | 1.5 mg/kg | Intravenous |