The Immunological Basis for Treatment Resistance to Anti-TNF Treatments
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|ClinicalTrials.gov Identifier: NCT01971346|
Recruitment Status : Completed
First Posted : October 29, 2013
Last Update Posted : December 6, 2017
|Condition or disease||Intervention/treatment||Phase|
|Psoriasis||Drug: etanercept||Phase 4|
Hypothesis: The balance between type I IFN and TNF determines the response to anti-TNF treatment. The goal of the proposed study is to address this hypothesis and demonstrate that the strength of the type I IFN signature in psoriatic skin is the major determinant of the clinical response to anti-TNF treatment.
Purpose: Determine the strength of the type I interferon and TNF signal in psoriatic skin prior to and during treatment with etanercept and correlate with degree of clinical improvement.
Study Population: up to 50 subjects, men or women over the age of 18 with clinically stable plaque psoriasis, who meet the wash out requirements and other exclusion criteria
Psoriatic patients will receive 100 mg etanercept per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months.
Procedures: Urine pregnancy test, TB test, photography, Physical Examinations, Skin Examinations, Study Drug, Peripheral blood and biopsies
Anticipated Results: We expect that patients with strong IFN-α signature in psoriatic skin along with weak TNF-α signature will have minimal response to anti-TNF treatment, while patients with the opposite pattern, weak IFN and strong TNF signature, will have significant clinical improvement.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||71 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Immunological Basis for Treatment Resistance to Anti-TNF Treatments|
|Actual Study Start Date :||March 13, 2014|
|Actual Primary Completion Date :||November 1, 2017|
|Actual Study Completion Date :||November 1, 2017|
100 mg Etanercept injections per week for 3 months.
100 mg Etanercept injections per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months
Other Name: ENBREL
- change in Psoriasis Area and Severity Index (PASI) score [ Time Frame: 12 weeks ]Change in Psoriasis Area and Severity Index (PASI) score from baseline to week 12 will be calculated. The PASI Score will range from 0-72 at each timepoint. A cumulative score reflecting change in PASI during the course of etanercept treatment will be calculated for each patient. This score will then be treated as a continuous response variable, and we will use robust linear modeling to test whether scores are significantly associated with baseline TNF-α signal, baseline IFN-α signal, and/or an interaction between these two signals.
- TNF-alpha/IFN-alpha signal strength [ Time Frame: 12 Weeks ]Strength of TNF-alpha and IFN-alpha signatures will be measured in blood and skin of study subjects at initiation, during and after treatment. The TNF and IFN signals scores are arbitrary parameters calculated from the proportion and fold changes of TNF and IFN specific genes that are differentially expressed in psoriatic skin. These scores are represented as a ratio. The values can range from 0 to infinite but most fall within a range of 0.25 and 10-fold.The strength of these signals in skin will be done using bioinformatic approach quantifying transcriptional signature of these cytokines whereas blood-derived values will be based on serum concentration of these two cytokines. The strength of the cytokine signals in blood and skin will be treated as a response variable in a univariate repeated measure analysis of variance, with PASI response profile and time as covariates
- Psoriasis Area and Severity Index Response profile [ Time Frame: 12 Weeks ]Subjects will be categorized according to improvement in Psoriasis Area and Severity Index (PASI) score: responders (greater than 75% reduction in PASI from baseline), intermediate-responders (those with greater than 25% and less than 75% reduction in PASI from baseline), and non-responders (less than 25% reduction in PASI from baseline).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01971346
|United States, Michigan|
|University of Michigan Department of Dermatology|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Johann Gudjonsson, MD PhD||University of Michigan|