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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
Etanercept will be administered subcutaneously at a dose of 50 mg weekly and will be discontinued at the primary endpoint (48 weeks).
Methotrexate will be administered orally at a starting dose of 15 mg and will be increased to 25mg weekly at 2 weeks.
Sulfasalazine will be added at weeks 8,12,16 or 20 if the subject fails to achieve low disease activity, administered orally at a dose of 1g twice daily. Will be discontinued if starting etanercept at 24 weeks.
Institute of Rheumatic & Musculoskeletal Medicine, Chapel Allerton Hospital
Leeds, West Yorkshire, United Kingdom
Clinical remission
Proportion of patients that achieve clinical remission (Disease activity Score, DAS28 \<2.6) at 48 weeks, following either treatment strategy.
Time frame: 48 weeks
Change in MRI synovitis
Change in MRI synovitis between baseline and 48 weeks.
Time frame: baseline and week 48
CDAI (clinical disease activity index)
Change in CDAI score from baseline at weeks 12, 24, 48 and 96
Time frame: weeks 12, 24, 48 and 96
SDAI (simplified disease activity index)
Change in SDAI score from baseline at weeks 12, 24, 36 \& 48.
Time frame: weeks 12, 24, 48 and 96
ACR(American College of Rheumatology) response scores
ACR response score from baseline at weeks 12, 24, 48 and 96
Time frame: weeks 12, 24, 48 and 96
EULAR(European League Against Rheumatism)response criteria
EULAR response score from baseline
Time frame: weeks 12, 24, 48 and 96
Physical function, assessed by HAQ(health assessment questionnaire)
Time frame: weeks 12, 24, 48 and 96
Quality of life scores assessed by RA-QoL(RA quality of life questionnaire)
Time frame: weeks 12, 24, 48 and 96
Work instability, assessed by RA-WIS(RA work instability questionnaire)
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Hydroxychloroquine will be added at weeks 8,12,16 or 20 if the subject fails to achieve low disease activity, administered at a dose of 200mg daily. Will be discontinued if starting etanercept at 24 weeks.
Etanercept will be added at 24 weeks, if a subject fails to achieve clinical remission,at a dose of 50 mg weekly and will be discontinued at 48 weeks with the exception of those patients who are eligible to continue according to local prescribing guidelines (NICE guidelines)
Methotrexate will be administered orally at a starting dose of 15 mg weekly, increasing to 20mg and 25mg weekly at weeks 4 and 8 respectively.
Time frame: weeks 12, 24, 48 and 96
HRUS (High Resolution Ultrasound)
Change in HRUS from baseline
Time frame: weeks 0, 12, 24 and 48
Radiographic scores
Change in joint damage assessed by modified Sharp score.
Time frame: weeks 48 and 96
Immunological parameters in blood sample
Change in immunological markers of inflammation between baseline and weeks 12, 24 and 48.
Time frame: weeks 0, 12, 24 and 48
Immunological parameters in synovial tissue
Change in immunological markers of inflammation between baseline and weeks 24 and 48.
Time frame: weeks 0, 24, +/- 48