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

NCT ID: NCT01276314

Last Updated: 2017-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2015-05-31

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.

Conditions

Drug Hypersensitivity

Keywords

SCAR; anti-TNF-a

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

anti- TNF-a treatment

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

Group Type: EXPERIMENTAL

anti- TNF-a

Intervention Type: DRUG

25mg BIW, SC

control group

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.

Group Type: ACTIVE_COMPARATOR

Prednisolone

Intervention Type: DRUG

1-1.5 mg / kg / day

Interventions

anti- TNF-a

25mg BIW, SC

Intervention Type: DRUG

Prednisolone

1-1.5 mg / kg / day

Intervention Type: DRUG

Other Intervention Names

Etanercept; steroid therapy

Eligibility Criteria

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.

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Science and Technology Council, Taiwan

OTHER_GOV

Sponsor Role: collaborator

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wen-Hung Chung, MD

Role: STUDY_CHAIR

Department of Dermatology, CGMH

Locations

Department of Dermatology, Chang Gung Memorial hospital

Taipei, , Taiwan

Countries

Taiwan

References

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.

Reference Type: BACKGROUND

PMID: 11048976 (View on PubMed)

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.

Reference Type: RESULT

PMID: 17919775 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24928706 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29400697 (View on PubMed)

Other Identifiers

97-1413A3

Identifier Type: -

Identifier Source: org_study_id