Efficacy of Humira in Behcet Patients With Arthritis

Study Overview
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Brief Summary
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Hypothesis - Behcet's disease is a multisystemic chronic relapsing inflammatory disease, classified among the vasculitides. The clinical manifestations include mucocutaneous lesions, articular, ocular, vascular, gastrointestinal and/or central nervous system involvement. The aetiology of Behcet's disease is unknown, however. Experimental evidence suggests that TNF-α may play an important role in the pathogenesis of the disease. To date, case reports and small open-short term studies report the efficacy of anti-TNFα therapy (Infliximab and Etanercept), especially regarding ocular and mucocutaneous involvement in Behcet. There are no double blind long term studies on larger number of patients regarding the efficacy of anti-TNFα, especially Humira in healing arthritis +/- other manifestations of the disease.

Detailed Description
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Study Design (including visit schedule, dosing and procedures/methods): Screen visit, 1st visit -treatment initiation, follow-up visits - after 1 month and afterwards every 8 weeks for 24 weeks. Screen visit: informed consent, medical history,inclusion and exclusion criteria, pregnancy test, vital signs, physical examination, joint evaluation (no. of tender joints, no. of swollen joints), patient/investigator global disease activity, pain VAS, HAQ, Behcet Disease Current Activity Forms (BDACF), ECG, PPD and chest X-ray screening for tuberculosis, routine labs (performed at local HMO as a routine follow-up of the patient treatment with DMARD's): CBC, blood chemistry, ESR, CRP, urinalysis, HbsAg and AntiHCV, immunology labs (rheumatoid factor, anti-CCP, anti nuclear antibody - ANA). An induration of greater than 5 mm will be considered a positive PPD reaction. Follow up visits .: Vital signs, joint evaluation, patient/investigator global disease activity, pain VAS, HAQ, BDACF, routine labs (performed at local HMO as a routine follow-up of the patient treatment with DMARD's): CBC, blood chemistry, ESR, CRP, urinalysis, research blood samples for storage.

Official Title
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Efficacy of Humira in Behcet Patients With Arthritis

Conditions
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Arthritis; Behcet

Intervention / Treatment
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* Drug: Adalimumab (Humira)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able and willing to give written informed consent and comply with the requirements of the study protocol. Patients with Behcet disease ,who fulfilled the International Study group criteria for Behcet Disease. Experienced an inadequate response to previous or current treatment with one or more DMARDs because of inadequate efficacy or side effects. DMARDS and/or corticosteroids (< or equivalent to 10mg/d prednisone) permitted if stable for at least 4 weeks prior to screening. NSAIDs permitted if stable for at least 2 weeks prior to screening. Active peripheral arthritis at screening (tenderness and swelling of at least 3 small joints or one large joint) OR axial involvement (active enthesitis or spondylitis) Age 18-80 years. If female and of childbearing potential, a negative urine pregnancy test within 2 weeks prior to therapy, and using reliable means of contraception. Exclusion Criteria: Rheumatic autoimmune disease other than Behcet (Rheumatoid arthritis, SLE, scleroderma, etc). Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders. Known active bacterial, viral, fungal, mycobacterial or other infection, or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening. History of lymphoproliferative or hematologic malignancy. History of any other type of cancer in the past 5 years.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab, Behcet with arthritis<br> | Drug: Adalimumab (Humira)<br>* Open label pilot trial. The study includes 3 phases : Open label treatment period of 24 weeks. Extension follow -up (3 years): Patients who responded well to study drug and their disease relapsed within the first 12 weeks following study drug interruption will be eligible to receive the study drug for 3 years in order to comply with the Israeli Ministry of Health requirements. Safety follow-up: For patients who withdraw from either the open label treatment period or extension period, for another 24 weeks.<br>* Other names: Anti TNF monoclonal antibodies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in DAS28 | The proportion of patients with improvement in arthritis (DAS 28) at week 24 -changes from screening in DAS 28 , HAQ, , CRP. ANOVA analysis and descriptive statistics. An interim evaluation of the above parameters will be performed at week 16 (visit 4) and yearly afterwards for 3 more years in those patients who will continue drug study during the extension period | Week 24 |