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

Not Applicable

Completed

• Conditions: Drug Hypersensitivity
• Interventions: Drug: anti- TNF-a; Drug: Prednisolone

• Registration Number: NCT01276314
• Lead Sponsor: Chang Gung Memorial Hospital

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-07-05
• Study First Submitted QC: 2011-01-11
• Study First Posted: 2011-01-13
• Status Verified: 2014-12
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Results First Submitted: 2017-11-03
• Results First Submitted QC: 2017-12-17
• Last Update Submitted: 2017-12-17
• Results First Posted: 2017-12-19
• Last Update Posted: 2017-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 135

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
anti- TNF-a treatment	anti- TNF-a	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
control group	Prednisolone	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.

Primary Outcome Measures

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

Trial Locations

Locations (1)

Department of Dermatology, Chang Gung Memorial hospital; 🇨🇳 Taipei, Taiwan