Rheumatoid Arthritis
Conditions
Interventions
See section study design.
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Newly diagnosed, DMARD-naive RA patients, according to 2010 criteria - Age >=18 years
Exclusion criteria
Exclusion criteria: 1. Current or previous treatment of arthritis with DMARDs 2. Glucocorticoids (GCs) in the 3 months prior to randomization 3. (Relative) contraindications for study medication: a. Evidence of ongoing infectious or malignant process obtained within 3 months prior to screening and evaluated by a qualified health care professional. b. Pregnant or nursing (lactating) women. c. Female participants of child bearing potential and male participants whose partner is of child bearing potential who are not willing to ensure that they or their partner use effective contraception during the trial and for 3 months thereafter as in standard practice. d. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFT) such as aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/ serum glutamic pyruvic transaminase (ALT/SGPT), alkaline phosphatase, or serum bilirubin. The Investigator should be guided by the following criteria: Any single parameter may not exceed 2 x upper limit of normal (ULN). A single parameter elevated up to and including 2 x ULN should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment/randomization, to rule out laboratory error. e. History of renal trauma, glomerulonephritis, or subjects with one kidney only, or a glomerular filtration rate (GFR)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary outcomes for the clinical effectiveness consists of 2 parts, namely the difference in (1) proportion of patients using a b- or tsDMARD after 10 months of treatment and (2) disease activity, measured with the disease activity score (DAS) over time. The DAS is a pooled index that involves the incorporation of a graded 53-joint count for tenderness (Ritchie Articular Index, RAI), a 44-joint count for swelling, an erythrocyte sedimentation rate (ESR) and general health (GH, measured with a VAS 0 - 100mm) into a formula to obtain a numerical indicator of disease activity. The DAS formula is 0.53938*(RAI) + 0.06465(SJC44) + 0.33ln(ESR) + 0.00722(GH). Thresholds for remission and moderate-to-high disease activity for DAS are respectively =2.4. Our tailor-made management approach is superior to routine care if treatment goals (DAS | — |
Secondary
| Measure | Time frame |
|---|---|
| For our secondary endpoints the effectiveness after 10 months and over time, from a clinical, patient and societal perspective, will be compared between our tailor-made management approach and routine care. Clinical outcomes: • Disease activity (states) at 10 months, measured with the DAS. The DAS is a pooled index that involves the incorporation of a graded 53-joint count for tenderness (Ritchie Articular Index, RAI), a 44-joint count for swelling, an erythrocyte sedimentation rate (ESR) and general health (GH, measured with a VAS 0 - 100mm) into a formula to obtain a numerical indicator of disease activity. The DAS formula is 0.53938*(RAI) + 0.06465(SJC44) + 0.33ln(ESR) + 0.00722(GH). Thresholds for remission and moderate-to-high disease activity for DAS are respectively =2.4. • To investigate whether (changes in) biomarker(s) (levels) can adequately predict treatment response. For this, blood (sera, plasma and whole blood) will be collected at the indicated time points and stored at -80C. Inflammation markers will be measured using the Olink inflammation panel (92 proteins). In addition, immune pathway analysis will be performed on whole blood using RNAseq analysis. Total RNA will be isolated and transcriptomic analysis will be performed using RNA-seq. Moreover, the phenotype of immune cells will be analysed using multi-color flow cytometry on isolated PBMCs. For all three approaches (biomarkers, immune pathway analysis and immune cell phenotyping) the focus will be on comparing ACPA negative with positive and treatment responders with non-responders. Patient reported outcomes (PROs): • Self-reported disease activity, measured with the Routine Assessment of Patient Index Data 3 (RAPID3). Thresholds for remission and moderate-to-high disease activity are respectively =2 if the 0 - 10 scale is used. • Morning stiffness (severity and duration), measured with a 10-point Likert scale • General Health, measured with a visual analogue scale | — |
Countries
Netherlands
Outcome results
None listed