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

Drug Hypersensitivity Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01276314
• Other study ID #: 97-1413A3
• Status: Completed
• Phase: N/A
• First received: July 5, 2009
• Last updated: December 17, 2017
• Start date: January 2009
• Est. completion date: May 2015

Study information

• Verified date: December 2014
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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-a 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.

Related Conditions & MeSH terms

• Drug Hypersensitivity
• Drug-Related Side Effects and Adverse Reactions
• Hypersensitivity

Intervention

Drug:
• anti- TNF-a
25mg BIW, SC
• Prednisolone
1-1.5 mg / kg / day

Locations

Country	Name	City	State
Taiwan	Department of Dermatology, Chang Gung Memorial hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital	National Science Council, Taiwan

Country where clinical trial is conducted

Taiwan, 

References & Publications (3)

Paquet P, Paquet F, Al Saleh W, Reper P, Vanderkelen A, Piérard GE. Immunoregulatory effector cells in drug-induced toxic epidermal necrolysis. Am J Dermatopathol. 2000 Oct;22(5):413-7. — View Citation

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. — View Citation

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 Aca — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	One to two months for SJS/TEN cases, and one to six months for DRESS cases.