The main aim of the study is to determine whether TNFi instituted as first-line therapy in
early RA confers better outcomes (clinical, structural and immunological) compared to
delayed TNFi start; implying particular dominance of TNF in early disease, a changing role
of TNF with disease duration and hence, confirmation of a biological window of opportunity.
Change in MRI synovitisCDAI (clinical disease activity index)
SDAI (simplified disease activity index)
ACR(American College of Rheumatology) response scores
EULAR(European League Against Rheumatism)response criteria
Physical function, assessed by HAQ(health assessment questionnaire)
Quality of life scores assessed by RA-QoL(RA quality of life questionnaire)
Work instability, assessed by RA-WIS(RA work instability questionnaire)
HRUS (High Resolution Ultrasound)
Radiographic scores
Immunological parameters in blood sample
Immunological parameters in synovial tissue
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Inclusion Criteria:
- Male and female patients aged between 18 and 80 years.
- Diagnosis of rheumatoid arthritis (new 2010 ACR/EULAR RA classification criteria).
- Symptom onset within the preceding 12 months.
- Patients with active RA at baseline: clinical evidence of synovitis (or imaging
evidence of synovitis in cases of uncertainty/subclinical disease) in hand and/or
wrist joints evaluable by ultrasound and MRI, and DAS28-ESR>3. 2.
- Seropositivity for anti-citrullinated peptide antibody (ACPA) and/or rheumatoid
factor. If ACPA and rheumatoid factor are both negative, presence of power Doppler
in at least 1 joint on ultrasound imaging.
- DMARD-naive (with the exception of previous exposure to hydroxychloroquine for an
indication other than RA).
- 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.
Exclusion Criteria:
- Previous treatment with DMARDs for the management of RA.
- Intramuscular or intra-articular (of non-target joint) corticosteroid within 28 days
of the screening visit; intra-articular steroid of the chosen target joint within 12
weeks of screening.
- Oral steroid of greater than 10mg prednisolone daily, or change in oral steroid dose
within 28 days of study drug initiation at the baseline visit.
- Use (including use as required) of more than one NSAID, change in NSAID or change in
dose of NSAID within 28 days of the baseline visit.
- Contraindications to MRI (e. g. pacemaker) or unable or unwilling to attend for all
imaging assessments. In patients with previous penetrating trauma to the eye, or
patients at high risk of previous metal foreign body injury to the eye (e. g.
welding), skull x-ray will be performed; these patients may be included in the
absence of residual metal fragments on x-ray.
- Pregnancy or breastfeeding.
- Other contraindications to TNFi as determined by local prescribing guidelines and
physician discretion, including:
- Active infection, open leg ulcers, previously infected prosthetic joint (unless
completely removed), septic arthritis in last year, HIV, Hepatitis B or
Hepatitis C carriers, previous malignancy within 10 years (except basal cell
carcinoma), severe heart failure (New York Heart Association grade 3 or more),
any history of demyelinating disease, uncontrolled diabetes, pulmonary fibrosis,
bronchiectasis, previous PUVA therapy (of >1000 Joules), history of TB or
evidence of latent TB on chest x-ray/TB testing (in the latter event, a patient
may be included if treated with isoniazid and pyridoxine one month before
starting the study and for a further 6 months whilst on study treatments).
- History of other significant medical conditions, including:
- Severe pulmonary disease, defined as requiring previous hospital admission or
supplemental oxygen.
- Active or severe cardiovascular disease: uncontrolled hypertension, myocardial
infarction within 12 months of screening, unstable angina within 6 months of
screening.
- Other immunodeficiency disorders.
- Connective tissue diseases, e. g. primary Sjogren's syndrome, systemic sclerosis,
systemic lupus erythematosus, polymyositis.
- Psoriasis.
- Renal impairment (creatinine ≥ 175µmol/L).
- Blood disorders: neutropenia (neutrophils < 2. 0 x 109/L), thrombocytopenia
(platelets < 125 x 109/L), or anaemia (haemoglobin < 8 g/dL).
- Abnormal liver function (alanine transaminase, ALT > 3 x upper limit of normal).
- Planned surgery within the study period which is expected to require omission of any
study medication of 28 days or more.