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| Name | Class |
|---|---|
| National Science and Technology Council, Taiwan | OTHER_GOV |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| anti- TNF-a treatment | Experimental |
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 | Active Comparator |
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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anti- TNF-a | Drug | 25mg BIW, SC |
|
|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wen-Hung Chung, MD | Department of Dermatology, CGMH | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Dermatology, Chang Gung Memorial hospital | Taipei | 105 | Taiwan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 11048976 | 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. | |
| 17919775 | Result | 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. |
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We totally recruited 140 participants, but only 135 SCAR participants (including 91 SJS/TEN patients and 44 DRESS patients) were enrolled to analyze. 5 participants in the control group were not included to analyze (3 cases failed a screening with CD4<200 cells/mm3 and 2 cases as diagnosis change).
SCAR patients were enrolled in the clinical trial from 2009 to 2015 at Chang Gung Memorial Hospital in Taiwan.
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| ID | Title | Description |
|---|---|---|
| FG000 | Anti- TNF-a Treatment (SJS/TEN) |
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 anti-TNF a: 25mg BIW, SC |
| FG001 | Control Group (SJS/TEN) |
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. |
| FG002 | Anti- TNF-a Treatment (DRESS) |
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 anti-TNF a: 25mg BIW, SC |
| FG003 | Control Group (DRESS) |
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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
A total of 135 SCAR patients (including 91 SJS/TEN cases and 44 DRESS cases) were enrolled to analyze.
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| ID | Title | Description |
|---|---|---|
| BG000 | Anti- TNF-a Treatment (SJS/TEN) |
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 anti-TNF a: 25mg BIW, SC |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | We determined if the enrolled participants had SJS/TEN and DRESS using the criteria and histopathological examinations. | Posted | Median | Full Range | days | One to two months for SJS/TEN cases, and one to six months for DRESS cases. |
|
one to two months
The endpoints of serious adverse event and adverse event were assessed for three weeks after discharge.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Anti- TNF-a Treatment (SJS/TEN) |
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 anti-TNF a: 25mg BIW, SC |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sepsis | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Drug Hypersensitivity Clinical and Research Center, Laboratory of Dr. Wen-Hung Chung, | Chang Gung Memorial Hospital, Linko | 886-3-328-1200 | 8494 | kiruamairo@gmail.com |
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| ID | Term |
|---|---|
| D004342 | Drug Hypersensitivity |
| D002921 | Cicatrix |
| ID | Term |
|---|---|
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D000068800 | Etanercept |
| D011239 | Prednisolone |
| ID | Term |
|---|---|
| D007141 | Immunoglobulin Fc Fragments |
| D007128 | Immunoglobulin Fragments |
| D010446 | Peptide Fragments |
| D010455 | Peptides |
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| Prednisolone | Drug | 1-1.5 mg / kg / day |
|
|
| 24928706 | Result | 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. |
| 29400697 | Derived | 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. |
| BG001 | Control Group (SJS/TEN) |
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. |
| BG002 | Anti- TNF-a Treatment (DRESS) |
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 anti-TNF a: 25mg BIW, SC |
| BG003 | Control Group (DRESS) |
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. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Control Group (SJS/TEN) |
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. |
| OG002 | Anti- TNF-a Treatment (DRESS) |
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 anti-TNF a: 25mg BIW, SC |
| OG003 | Control Group (DRESS) |
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. |
|
|
|
| 5 |
| 48 |
| 15 |
| 48 |
| EG001 | Control Group (SJS/TEN) |
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. | 9 | 43 | 19 | 43 |
| EG002 | Anti- TNF-a Treatment (DRESS) |
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 anti-TNF a: 25mg BIW, SC | 2 | 22 | 8 | 22 |
| EG003 | Control Group (DRESS) |
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. | 5 | 22 | 8 | 22 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Bipolar disorder | Psychiatric disorders | Systematic Assessment |
|
| Upper GI hemorrhage | Gastrointestinal disorders | Systematic Assessment |
|
| Stridor, vocal cord palsy | Reproductive system and breast disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| GI hemorrhage (grade 2) | Gastrointestinal disorders | Systematic Assessment |
|
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| D013568 | Pathological Conditions, Signs and Symptoms |
| D000602 |
| Amino Acids, Peptides, and Proteins |
| D007127 | Immunoglobulin Constant Regions |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D018124 | Receptors, Tumor Necrosis Factor |
| D018121 | Receptors, Cytokine |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |