Humira in Rheumatoid Arthritis - Do Bone Erosions Heal? (HURRAH)

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

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.

Study Overview

• Status: Completed
• Conditions: Arthritis; Joint Diseases; Rheumatoid Arthritis
• Intervention / Treatment: Drug: Adalimumab (Humira)

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, DK-2100
    • Department of Rheumatology, Copenhagen University Hospital, Rigshospitalet
  • Copenhagen, Denmark, DK-2400
    • Department of Rheumatology, Bispebjerg University Hospital
  • Hellerup, Denmark, DK-2900
    • Department of Rheumatology, Gentofte University Hospital
  • Herlev, Denmark, DK-2630
    • Department of Rheumatology, Herlev University Hospital
  • Hvidovre, Denmark, DK-2650
    • Department of Rheumatology, Hvidovre University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: 1; Open-label, one arm only. All patients receiving active drug according to recommendations (adalimumab (Humira) 40 mg subcutaneously every other week).	Drug: Adalimumab (Humira); Adalimumab (Humira) 40 mg subcutaneously every other week; Other Names: Humira

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: Abbott
• Investigators: Principal Investigator: Mikkel Østergaard, Professor, Department of Rheumatology, Hvidovre University Hospital; Study Chair: Uffe Møller Døhn, M.D, Department of Rheumatology, Hvidovre University Hospital

Publications and helpful links

General Publications

• Krabbe S, Bolce R, Brahe CH, Dohn UM, Ejbjerg BJ, Hetland ML, Sasso EH, Chernoff D, Hansen MS, Knudsen LS, Hansen A, Madsen OR, Hasselquist M, Moller J, Ostergaard M. Investigation of a multi-biomarker disease activity score in rheumatoid arthritis by comparison with magnetic resonance imaging, computed tomography, ultrasonography, and radiography parameters of inflammation and damage. Scand J Rheumatol. 2017 Sep;46(5):353-358. doi: 10.1080/03009742.2016.1211315. Epub 2016 Sep 28.

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (ACTUAL): July 1, 2007
• Study Completion (ACTUAL): July 1, 2007

Study Registration Dates

• First Submitted: June 9, 2008
• First Submitted That Met QC Criteria: June 11, 2008
• First Posted (ESTIMATE): June 12, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): June 12, 2008
• Last Update Submitted That Met QC Criteria: June 11, 2008
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: Magnetic resonance imaging; Computed tomography; Rheumatoid arthritis; Radiography; Tumor necrosis factor alpha antagonists
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Joint Diseases; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: HUM 04-20