Patients with a severe psoriasis will be treated with Enbrel (Etanercept) 2 x 50 mg s.c. per week over 12 weeks (n = 6 patients). The treatment follows rigorously the approved label of the drug. The design of the study deviates from the approved label status in the only regard that within the course of the treatment per patient i) 5 skin biopsies with a horizontal diameter of 6 mm are taken in local anesthesia and ii) 4 peripheral venous blood drawings of 10 ml, each, are performed.
Conditions
Interventions
Trade Name: Enbrel 50 mg Fertigspritze (= ready for use syringe for s.c. injection)
Pharmaceutical Form: Injection*
Sponsors
Medical Faculty, Otto-von-Guericke-University Magdeburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: According to approved label status of Enbrel: Adult patients with moderate to severe plaque psoriasis, who have failed to respond to, or who have a contraindication to, or are intolerant of other systemic therapies including cyclosporin, methotrexate and PUVA. According to study protocol: The patient is able to understand the study and capable to give informed consent. Written informed consent. Age of more than 18 years. Psoriasis Area and Severity Index (PASI) of more than 10 or involvement of body surface by psoriasis for more than 10% or Dermatologic Life Quality Index (DLQI, according to Finlay and Kahn) of more than 10. Exclusion of an active or latent tuberculosis by negative tuberculosis-skin/-blood-test and chest x-ray. Consideration of the following wash-out-intervals before the start of study medication: i) 2 weeks for antipsoriatic topical drugs (vitamin D and analogues, tazarotene, corticosteroids, tar), ii) 4 weeks for conventional antipsoriatic systemic drugs (methotrexate, acitretin, fumarates and ciclosporin), iii) 4 weeks for UV-treatment, iv) 3 months for efalizumab, adalimumab, infliximab, and golilumab, v) 6 months for ustekinumab, and vi) 6 months for any investigational compound / drug. In case of treatment with a beta-blocker, ACE-inhibitor, anti-malaria drug (resochin), interferon or lithium: stable medication with these agents for at least 4 weeks before the start of the study medication. No foreseeable necessity for vaccinations during 4 weeks before the start of the study medication, during 16 weeks of study medication and during 8 weeks afterwards. Willingness to keep natural / sun light exposure adequately constant und to avoid the use of artificial UV exposition (solarium). Use of anticonception in female and male study participants under study medication. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: According to approved label status of Enbrel: Hypersensitivity against the active compound (i.e. etanercept) or any other compound of Enbrel or to latex of the lid of the Enbrel syringe. Sepsis or risk of sepsis. A treatment with Enbrel must not be initiated in patients with active infections, including chronic or localised infections. According to study protocol: Severe/relevant infections including infections by tuberculosis bacteria, HIV, hepatitis B or C virus. Cronic or relapsing infections in the history. Diseases favouring infections, e.g. severe or un-controlled diabetes mellitus. Intake of immunosuppressive agents / drugs. Treatment with anankinra (= Kineret) or abatacept (= Orencia) or sulfasalazin. Indication for a demyelinating disease (e.g. multiple sclerosis) in the patient´s history or in the history of a family member. Heart insufficiency (NYHA III/IV). Malignancies of recent relevance (incl. solid tumors, malignant hematopoetic diseases, lymphoproliferative diseases, non-melanocytic skin cancer). Blood dyscrasia (incl. severe anemia, leukopenia, thrombocytopenia, pancytopenia). Moderate or severe alcohol hepatitis. Treatment resistance to Enbrel. Intolerance to biologics. Autoimmune diseases coinciding with the formation of antinuclear antibodies. Precedent or current medication with azathioprine or 6-mercaptopurine. History of a Felty syndrome or of a splenomegaly in combination with leukocytopenia. Pregnancy. Breast feeding. Up-coming need for vaccination with live vaccine. Absolute criteria for premature discontinuation are: - Occurence of pregnancy. - Clinically significant worsening of disease - defined as an increase of PASI of > 50% as compared to the begin of study medication. - Grade 3 systemic toxicity. - Grade 4 adverse event or a serious adverse event thought to be related to study medication. - Serious infection (grade 3) incl. sepsis syndrome with hypotension. - Withdrawal of consent. - Significant exposure to varicella-virus. - Need for vaccination with live vaccine. The treatment may be discontinued under the following conditions: - Lack of subject compliance. - Significant protocol deviation. - Upon decision of the investigator due to serious other reasons.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Analysis of the inflammatory topoproteome of i) skin tissue and ii) peripheral blood mononuclear cells in psoriasis under etanercept treatment.;Secondary Objective: i) Analysis of change of Psoriasis Area and Severity Index (PASI), Physician´s Global Assessment (PGA), itch-score and Dermatologic Life Quality Index (DLQI) for evaluation of clinical efficacy, as well as treatment-response and treatment-non-response. ii) Evaluation of treatment safety.;Primary end point(s): The primary endpoint is the antipsoriatic treatment of the study participants with enbrel 2 x 50 mg s.c / week for 12 weeks. At that time point PASI-50-response and PASI-75-response will be recorded. The primary study parameters are the analysis of the inflammatory topoproteome in skin tissue and mononuclear cells of peripheral blood, respectively. | — |
Countries
Germany
Outcome results
None listed