Targeted treatment with etanercept plus methotrexate for early rheumatoid arthritis patients that have not received any treatment yet. The treatment is rationalised based on the normality of the T-cell stratification.
- Conditions
- Rheumatoid arthritisMusculoskeletal Diseases
- Registration Number
- ISRCTN17694963
- Lead Sponsor
- niversity of Leeds
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 106
1. Subject has a diagnosis of RA as defined by the new ACR/EULAR 2010 classification criteria
2. Newly diagnosed (within 12 weeks)
3. Active disease at screening (DAS28ESR =3.2 or clinical evidence of synovitis i.e. at least one swollen joint)
4. Anti-citrullinated protein antibody (ACPA) positive
5. Male & female subjects =18 years old
6. DMARD (disease modifying anti-rheumatic drug) naïve
7. No use of intra-muscular, intra-articular or oral corticosteroids 4 weeks prior to screening
8. All male and female subjects biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and 24 weeks after the end of the study period. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives.
9. Patients must have the capacity and be willing to provide written informed consent and comply with the requirements of the protocol
10. Subjects should be deemed to be in good health with respect to clinical examination and screening blood tests, including full blood count (FBC), urea and electrolytes (U&E), and liver functions tests (LFT) – see exclusion criteria for further details.
1. Use of any additional investigational medications or products within 4 weeks of screening (including prior to screening)
2. Use of intra-muscular/intra-articular or oral corticosteroids within 4 weeks prior to screening
3. Use of more than one NSAID, or increase in dose of NSAIDs within 24 hours before the screening visit.
4. Live vaccine within <4 weeks prior to screening
5. Pregnant/lactating women or planning pregnancy within 24 weeks of last protocol treatment
6. Planned surgery within the study period (requiring omission of study medication > 4 weeks
7. The presence of other comorbidities, which the physician deems as significant to interfere with evaluation (musculoskeletal condition such as osteoarthritis & fibromyalgia)
8. Diagnosis of another inflammatory arthritis or connective tissue disease (e.g. psoriatic arthritis or Ankylosing spondylitis, primary Sjögren’s syndrome, systemic sclerosis, systemic lupus erythematosus, polymyositis)
9. Concomitant severe infection requiring intravenous 4 weeks prior to screening
10. Any contraindication to conventional DMARD’s/anti-TNF therapy
11. Patients with abnormal liver function at the time of screening or abnormal blood tests as shown by:
11.1. Aminotransferase (AST) / alanine aminotransferase (ALT) > 3x upper limit of normal (ULN) OR Bilirubin 50µmol/L
11.2. Serum Creatinine > 175 umol/L
11.3. eGFR below 30ml/L/min/1.73m²
11.4. neutrophils < 2000 x 10^6/L
11.5. Platelets < 125 x 10^9/L
11.6. Haemoglobin < 90 g/L for males and < 85 g/L for females
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method umber of patients in clinical remission (DAS28ESR =2.6) at 24 weeks measured using a combination of: Patient general health assessment on a visual analog scale (0-100 mm), IJA count of 28 joints for swelling and tenderness, and ESR value
- Secondary Outcome Measures
Name Time Method 1. Number of patients in clinical remission (DAS28ESR =2.6) after 12 weeks measured using a combination of: Patient general health assessment on a visual analog scale (0-100 mm), IJA of 28 joints for pain and tenderness, and ESR value<br>2. Patient-reported outcome measures after 12 weeks & 24 weeks:<br>2.1. Elderly Mobility Scale (EMS)<br>2.2. VAS scales from 0 to 100 to measure General health, global pain, disease activity<br>2.3. HAQ-DI, a measure of the ability to perform daily activities<br>3. Number of patients in imaging remission (PD=0) after 24 weeks measured using ultrasound scan<br>4. Number of patients with normal naïve CD4+ T-cells at 24 weeks measured using flow cytometry<br>5. Cumulative amount of corticosteroid use at 24 weeks usually measured in prednisolone equivalent cumulative dose