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

Chang Gung Medical Foundation

Status: Completed

Conditions: Drug Hypersensitivity

Treatments: Drug: anti- TNF-a; Drug: Prednisolone

Study type: Interventional

Funder types: Other

Identifiers

NCT01276314

97-1413A3

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 135 patients

Sex: All

Ages: 4+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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.
2. Male or female patient aged more than 4 years.
3. Inform consent obtained.

Exclusion criteria

1. Pregnant or breastfeeding female.
2. Allergic to any anti-TNF-α biological product.
3. Active or latent tuberculosis confirmed with Chest X-ray.
4. Severe active infection and septicemia.
5. Active Hepatitis B or C carrier.
6. Suspected HIV carrier with CD4 count less than 200.
7. Patient with poor compliance or with safety concerns judged by investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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135 participants in 2 patient groups

anti- TNF-a treatment

Experimental group

Description:

1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF 2. Fill out the case report form 3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis 4. 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

Treatment:

Drug: anti- TNF-a

control group

Active Comparator group

Description:

1. Meet the conditions of inclusion and exclusion, seek the consent of the patient, and fill out the ICF 2. Fill out the case report form 3. Blood test and physiological assessment, and do TNF-alpha serum concentration and peripheral blood mononuclear spherical cDNA expression analysis 4. 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.

Treatment:

Drug: Prednisolone