Evaluation of TNF-α Blockade Effect in Patients With Severe Cutaneous Adverse Drug Reactions

Study Overview
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Brief Summary
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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.

Detailed Description
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Severe cutaneous adverse drug reactions, including Toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome(SJS), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a life threatening disease. There is no gold standard in the therapy of SCAR. Treatment with high dose systemic corticosteroids is controversial. Although there have been recent reports of success with various therapies such as plasmapheresis and high-dose intravenous immunoglobulins, their efficacy is not yet proven. Assessment of these therapies is difficult because of their non-specific immunosuppressant or immunomodulating modes of action. Recent studies have shown evidence of the pathogenetic importance of tumour necrosis factor (TNF)-a, suggesting a new therapeutic approach in selective blockade of TNF-a using specific antibodies. We report successful treatment TEN using monoclonal IgG anti-TNF-antibodies. 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.

Official Title
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Evaluation of TNF-α Blockade Effect in Patients With Severe Cutaneous Adverse Drug Reactions (SCAR)

Conditions
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Drug Hypersensitivity

Intervention / Treatment
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* Drug: anti- TNF-a
* Drug: Prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patient with clinical and pathological diagnoses of severe cutaneous adverse drug reactions such as Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis or Durg reaction with eosinophilia and systemic symptoms. Male or female patient aged more than 4 years. Inform consent obtained. Exclusion Criteria: Pregnant or breastfeeding female. Allergic to any anti-TNF-α biological product. Active or latent tuberculosis confirmed with Chest X-ray. Severe active infection and septicemia. Active Hepatitis B or C carrier. Suspected HIV carrier with CD4 count less than 200. Patient with poor compliance or with safety concerns judged by investigator.

Ages Eligible for Study
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Minimum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti- TNF-a treatment<br>Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF Fill out the case report form Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis Etanercept administration: The experimental group received the first dose of Etanercept (25 mg) i.v., followed by two doses per week and maintain 2 to 3 weeks | Drug: anti- TNF-a<br>* 25mg BIW, SC<br>* Other names: Etanercept;|
| Active Comparator: control group<br>Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF Fill out the case report form Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis Drug administration: The control group of drug delivery: systemic intravenous steroid therapy, the dose is equivalent to prednisolone 1-1.5 mg / kg / day, according to the treatment of 3-4 days gradually decreased dose. | Drug: Prednisolone<br>* 1-1.5 mg / kg / day<br>* Other names: steroid therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skin Healing Time | Healing was defined as complete re-epithelialization (i.e., the complete absence of erosions). We recorded the time taken by the skin to heal. | One to two months for SJS/TEN cases, and one to six months for DRESS cases. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SCAR, anti-TNF-a