Rheumatoid Arthritis
Conditions
Brief summary
The TREMERA study focuses on patients with newly diagnosed, untreated, rheumatoid arthritis (RA). Recent international treatment recommendations emphasise the need to diagnose RA early and start treatment immediately (this being associated with better response rates); and to aim for the goal of remission i.e. the absence of signs and symptoms of active inflammatory disease activity which is associated with better outcomes for the patient. Remission is more achievable with significant treatment advances that have been made in the form of highly effective biologic therapies. Tocilizumab (TCZ) is a newly introduced biologic drug that is used in established RA. The TREMERA study primarily aims to investigate the biological changes seen in blood and tissue following TCZ therapy this will contribute to a better understanding of how the drug works as well as disease processes; and will also identify whether administering a biologic drug such as TCZ can also switch off immunological parameters associated with a disrupted immune system of RA. The study will assess the effectiveness of TCZ given on its own or in combination with methotrexate (MTX; a standard therapy usually given with biologic treatments)in patients with early onset RA to determine the proportion that achieve remission. This study also aims to find out how quickly remission can be achieved with TCZ and the depth of remission achieved. This will be done using usual clinical assessment but also imaging such as ultrasound and magnetic resonance imaging (MRI) which can detect inflammation not apparent on clinical assessment.
Interventions
DRUGTocilizumab
DRUGMethotrexate
Sponsors
Hoffmann-La Roche
University of Leeds
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of rheumatoid arthritis (2010 ACR/EULAR RA classification criteria) * Symptom duration ≤12months * No previous disease modifying antirheumatic drug (DMARD) therapy * Active RA at baseline (defined as: DAS28 ≥ 3.2) * Active hand and/or wrist joint evaluable by US and MRI (with no planned surgery during the study period) * Patients without any contraindication to MRI
Exclusion criteria
* Patients unwilling or unable to receive MTX for the duration of the study. * Patients with inflammatory joint disease of different origin, mixed connective tissue disease, Reiter's syndrome, psoriatic arthritis, systemic lupus erythematosis, or any arthritis with onset prior to 16 years of age. * Suspicion of diagnosis of tuberculosis (TB): positive quantiferon +/abnormal chest x-ray, as per clinician judgement. Prior history of TB with confirmed full chemotherapy +/latent TB adequately treated may be included as per physician's discretion. * Intramuscular, oral or intraarticular (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. * Patients with serious infections within 3 month of enrolment (screening) or persistent infections. * Patients at significant risk of infection (e.g. leg ulceration, indwelling urinary catheter, septic joint within 1 year (or ever if prosthetic joint still in situ). * Known positive serology for hepatitis B or C, or HIV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate change in expression of JAK 1 and 3 (as well as STAT and p38 MAPK). | To week 60 | Changes up to week 60 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sharp score on plain radiographs | Week 48. | Change in modified Sharp score on plain radiographs |
| Reduction in inflammation in each treatment arm using ultrasound | To week 48 | Establish reduction in inflammation in each treatment arm using ultrasound using grey scale power doppler |
| Disease Activity Score (DAS): DAS28/44 remission | To week 48 | Proportion of patients achieving DAS28/44 remission |
| Questionnaires and research tools | Week 48 | Using tools including DAS28/44, SDAI, CDAI |
| Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire | To week 48 | The change in RAQoL from baseline |
| Bone densitometry | Week 48. | Bone densitometry scan of hands, spine, femoral neck |
| Health Assessment Questionniaire (HAQ) scores | To week 48 | The change from baseline in HAQ scores. |
| VAS scores questionnaire | To week 48 | The change in VAS scores for pain, disease activity |
Other
| Measure | Time frame | Description |
|---|---|---|
| MRI sub-study (separately consented) - optional | To week 48 | Establish if reduction in RA MRI Scoring system (RAMRIS) synovitis score |
| Cardiovascular sub-study (separately consented) - optional | To week 48 | Change in cardiovascular measures on cardiac MRI and serum biomarkers |
Countries
United Kingdom
Outcome results
None listed