Humira in Rheumatoid Arthritis - Do Bone Erosions Heal?

Rheumatoid Arthritis Clinical Trial

— HURRAH  

Official title:

Can Bone Erosions Heal in Adalimumab (Humira) Treated Rheumatoid Arthritis Patients. An Imaging Study Using Computed Tomography and Magnetic Resonance Imaging.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00696059
• Other study ID #: HUM 04-20
• Status: Completed
• Phase: Phase 4
• First received: June 9, 2008
• Last updated: June 11, 2008
• Start date: August 2004
• Est. completion date: July 2007

Study information

• Verified date: June 2008
• Source: Hvidovre University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Ethics CommitteeDenmark: National Board of HealthDenmark: Danish Medicines AgencyDenmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical Trial Summary

Studies on tumor necrosis factor alpha antagonist (anti-TNF) therapy in rheumatoid arthritis (RA) patients have found that erosive damage may "heal" in some RA patients treated with anti-TNF. Repeated examinations of adalimumab (Humira) treated RA patients, using computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography (US) and radiography will allow detailed assessment of the extent of bone repair/healing during adalimumab (Humira) therapy.

Description:

Studies on tumor necrosis factor alpha antagonist (anti-TNF) therapy in rheumatoid arthritis (RA) patients have found that radiographic erosions scores decreased in some patients. This suggests that erosive damage may "heal" in some RA patients treated with anti-TNF. However, it is not clarified whether the reduced scores are caused by technical issues as observer variation and image acquisition differences. Furthermore, radiography of erosions is a 2D representation of a 3D pathology and therefore not ideal for visualizing healing, if present. Verification of erosion healing under anti-TNF therapy with adalimumab (Humira) by optimal imaging methods, would markedly influence our perception of the effect and potential of adalimumab (Humira) for modifying structural joint damage in RA. Magnetic Resonance Imaging (MRI), allowing high-resolution 3D visualization of bone damage as well as the inflammatory activity in the bone (bone marrow edema/osteitis), is more sensitive for visualization of bone erosions than radiography. Computed Tomography (CT) is a 3D radiographic imaging technique, which is not suited for assessment of inflammation, but can be considered a reference method for assessment of bone damage, due to its direct 3D visualization of calcified tissue. Internationally recommended MRI scoring systems as well as methods for estimation of erosion volumes have been developed, with participation by our research group. Ultrasonography (US), even though less validated, is more sensitive than radiography and comparable to MRI in detecting bone erosions in RA joints. Additionally, US provides visualisation of soft tissue changes and synovitis, using gray-scale and Doppler US.

Repeated MRI, CT, US and radiographic examinations of RA joints with mild to moderate radiographic damage under adalimumab (Humira) therapy will allow detailed assessment of the extent of bone repair/healing during adalimumab (Humira) therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: July 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis according to the American College of Rheumatology 1987 criteria

• Moderate or severely active RA, defined as a DAS28(CRP)> 3.2

• Moderate radiographic structural joint damage, defined as Larsen grade 2-3, in = 2 wrist and/or MCP joints

• No previous biological therapy

• Clinical indication for biological therapy, according to the treating physician

• Treatment with methotrexate and folic acid for at least 4 weeks prior to inclusion

• No history of tuberculosis, and no signs of tuberculosis at chest radiograph or Mantoux test.

• No contra-indications for TNF-alpha antagonist treatment

• Co-operability of the patient, including that the patient is willing and able to comply with the treatment and scheduled follow-up visits and examinations

• Oral and signed informed consent by the patient

Exclusion Criteria:

• Acute infection, and known chronic viral infection such as HIV or hepatitis B and C

• Other DMARDs than methotrexate within last 4 weeks before inclusion

• Intramuscular or intraarticular glucocorticoids within last 4 weeks before inclusion

• Oral treatment with prednisolone >10 mg per day

• Malignant lymphoma and other malignant disease

• Other serious concomitant diseases (uncontrolled/severe kidney, liver, haematological, gastrointestinal, endocrine, cardiovascular, pulmonary, neurological or cerebral disease (including demyelinating disease))

• Pregnancy and lactation. Patients must use safe anti-conception during the treatment.

• Development of SLE-like disease. Occurrence of positive ANA and/or anti-DNA antibodies without clinical symptoms is not considered a contra-indication.

• Contra-indications for MRI

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Joint Diseases
• Rheumatoid Arthritis

Intervention

Drug:
• Adalimumab (Humira)
Adalimumab (Humira) 40 mg subcutaneously every other week

Locations

Country	Name	City	State
Denmark	Department of Rheumatology, Bispebjerg University Hospital	Copenhagen
Denmark	Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet	Copenhagen
Denmark	Department of Rheumatology, Gentofte University Hospital	Hellerup
Denmark	Department of Rheumatology, Herlev University Hospital	Herlev
Denmark	Department of Rheumatology, Hvidovre University Hospital	Hvidovre

Sponsors (2)

Lead Sponsor	Collaborator
Hvidovre University Hospital	Abbott

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	By means of computed tomography and magnetic resonance imaging to investigate if repair of bone erosion occurs in rheumatoid arthritis joints during adalimumab (Humira) therapy		52 weeks	No