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Humira in Rheumatoid Arthritis - Do Bone Erosions Heal?

Phase 4
Completed
Conditions
Rheumatoid Arthritis
Arthritis
Joint Diseases
Interventions
Registration Number
NCT00696059
Lead Sponsor
Hvidovre University Hospital
Brief 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.

Detailed 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 & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
52
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

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
1Adalimumab (Humira)Open-label, one arm only. All patients receiving active drug according to recommendations (adalimumab (Humira) 40 mg subcutaneously every other week).
Primary Outcome Measures
NameTimeMethod
By means of computed tomography and magnetic resonance imaging to investigate if repair of bone erosion occurs in rheumatoid arthritis joints during adalimumab (Humira) therapy52 weeks
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (5)

Department of Rheumatology, Hvidovre University Hospital

🇩🇰

Hvidovre, Denmark

Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet

🇩🇰

Copenhagen, Denmark

Department of Rheumatology, Bispebjerg University Hospital

🇩🇰

Copenhagen, Denmark

Department of Rheumatology, Gentofte University Hospital

🇩🇰

Hellerup, Denmark

Department of Rheumatology, Herlev University Hospital

🇩🇰

Herlev, Denmark

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