Efficacy of Humira in Behcet Patients With Arthritis

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.

Study Overview

• Status: Completed
• Conditions: Arthritis; Behcet
• Intervention / Treatment: Drug: Adalimumab (Humira)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 31096
    • Rheumatology Unit, Rambam Health Care Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Able and willing to give written informed consent and comply with the requirements of the study protocol.
2. Patients with Behcet disease ,who fulfilled the International Study group criteria for Behcet Disease.
3. Experienced an inadequate response to previous or current treatment with one or more DMARDs because of inadequate efficacy or side effects.
4. 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.
5. 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)
6. Age 18-80 years.
7. 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:

1. Rheumatic autoimmune disease other than Behcet (Rheumatoid arthritis, SLE, scleroderma, etc).
2. Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.
3. 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.
4. History of lymphoproliferative or hematologic malignancy. History of any other type of cancer in the past 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Adalimumab, Behcet with arthritis

Drug: Adalimumab (Humira); 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.; Other Names: Anti TNF monoclonal antibodies

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus
• Collaborators: Abbott
• Investigators: Principal Investigator: Yolanda Braun, MD, Rheumatology Unit, Rambam Health Care Campus, B. Rappaport Faculty of Medicine, Technion - Institute of Technology, Israel

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: December 20, 2011
• First Submitted That Met QC Criteria: December 21, 2011
• First Posted (Estimate): December 22, 2011

Study Record Updates

• Last Update Posted (Estimate): October 26, 2016
• Last Update Submitted That Met QC Criteria: October 25, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Stomatognathic Diseases; Mouth Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Vasculitis; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Arthritis; Behcet Syndrome; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: 0488-09RMB; A06-197 (Other Identifier: Protocol Number of Collaborator - Abbott Company)