ADalimumab in Persistent Early Oligoarthrits Study (ADEOS)

Study Overview
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Brief Summary
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The purpose of this study is to investigate adalimumab, a drug that is currently licensed for treatment of patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and inflammatory bowel disease (Crohn's disease). It is a protein (human monoclonal antibody) that is designed to block the effects of an inflammatory cytokine, tumour necrosis factor alpha (TNF alpha) which is a causative factor in joint inflammation. It is given as a subcutaneous injection. Management of established rheumatoid arthritis has been transformed with the use of TNFantagonists, the first in the class of biological agents. The benefits in early RA are also continuing to emerge. Oligoarthritis represents a subgroup of early inflammatory arthritis that warrants more effective treatment strategy including the potential to modulate the disease course and halt further progression. The TNFantagonists offer the potential of achieving this, justifying this initial investigation. Hence, this study is designed to establish the benefit of adalimumab in preventing progression of oligoarthritis. The primary aim of the study is to assess how many patients achieve remission i.e. no further evidence of joint inflammation or damage. The investigators will do this by including patients who present with inflammation of four or less joints who do not fulfil criteria for a definite arthritis condition such as rheumatoid arthritis. The investigators will perform clinical, laboratory (blood tests) and imaging assessments at regular intervals on these patients to check on safety of the study drug adalimumab and evaluate any changes in disease activity that may have resulted from use of adalimumab. All patients will receive treatment with a standard therapy (methotrexate) with randomisation of half of the patients to receive the active study drug, adalimumab as additional treatment for six months.

Official Title
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Prospective, Single-centre, Double-Blind, Randomised, Placebo-controlled Study Evaluating Efficacy of Adalimumab + Methotrextate Compared With Placebo + Methotrexate in Patients With Early Oligoarthritis (ADEOS)

Conditions
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Oligoarthritis

Intervention / Treatment
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* Drug: Adalimumab
* Drug: Methotrexate
* Drug: Placebo
* Drug: Folic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects presenting at the rheumatology clinic who meet all of the following criteria will be considered for enrolment into the study:- Male and female patients aged between 18 and 80 years. Oligoarthritis defined as inflammatory arthritis affecting ≤ 4 joints At least 1 large joint involvement (wrist, elbow, shoulder, knee or ankle) Disease duration of less than 12 months Patients on NSAIDs must have remained on an unchanged regimen for at least 28 days prior to study drug administration. Patients must be able and willing to comply with the terms of this protocol. Informed consent must be obtained in writing for all subjects at enrolment into the study. Exclusion Criteria: Patients who have > 12 months disease duration Exclude if DIP joint alone Evidence of osteoarthritis Diagnosis of gout Previous treatment with a DMARD therapy. Change in NSAID dose within the last 28 days Previous treatment with oral, intra-muscular or intra-articular steroid Patients unwilling or unable to receive adalimumab or MTX or both for the duration of the study. Planned surgery within 12 months of study initiation. Patients with moderate to severe heart failure Suspicion of diagnosis of tuberculosis (positive tuberculosis test (>5mm in duration if previous BCG or >10mm if no previous BCG) or abnormal chest x-ray)

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TNF-antagonist<br>Adalimumab, 40 mg, 2-weekly Methotrexate, rapid escalation to 25mg, weekly Folic Acid 5mg, 6 days a week | Drug: Adalimumab<br> <br> Drug: Methotrexate<br> <br> Drug: Folic Acid<br> <br> |
| Active Comparator: Placebo + MTX<br>Placebo, 2 weekly Methotrexate, rapid escalation to 25mg, weekly Folic Acid 5mg, 6 days a week | Drug: Methotrexate<br> <br> Drug: Placebo<br>* Placebo to replace adalimumab<br>Drug: Folic Acid<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients in remission at 24 weeks. | Number in remission at 24 weeks (absence of clinical-evidence synovitis (no tender/swollen joints) & CRP< 5mg/ml) | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response at weeks 12, 36, 48, 72 and 96 | Complete response (absence of clinical-evidence synovitis & CRP< 5mg/ml) at weeks 12, 36, 48, 72 and 96 | Weeks 12, 36, 48, 72 and 96. | 
| Disease Activity Score at weeks 12, 24, 36, 48, 72 and 96 | Disease Activity Score at weeks 12, 24, 36, 48, 72 and 96 | Weeks 12, 24, 36, 48, 72 and 96 | 
| Ultrasonographical features (erosions) at weeks 2 and 24 | Ultrasonographical features (erosions) at weeks 2 and 24 | Week 2 and 24 | 
| Health Assessment Questionnaire at weeks 0, 12 24, 36, 48, 72 and 96 | Health Assessment Questionnaire at weeks 0, 12 24, 36, 48, 72 and 96 | Week 0, 12 24, 36, 48, 72 and 96 | 
| EQ-5D (Euro-QoL) questionnaire at weeks 0, 12 24, 36, 48, 72 and 96 | EQ-5D (Euro-QoL) questionnaire at weeks 0, 12 24, 36, 48, 72 and 96 | Week 0, 12 24, 36, 48, 72 and 96 | 
| Work Instability Scale at weeks 0, 12, 24, 36, 48, 72 and 96 | Work Instability Scale at weeks 0, 12, 24, 36, 48, 72 and 96 | weeks 0, 12, 24, 36, 48, 72 and 96 | 
| Plain radiography at weeks -2, 24 and 96 | Plain radiography at weeks -2, 24 and 96 | weeks -2, 24 and 96 |