Rheumatoid Arthritis
Conditions
Interventions
Trade Name: RoActemra
Product Name: Tocilizumab
Product Code: RoActemra
Pharmaceutical Form: Concentrate and solvent for solution for infusion
Sponsors
The University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Diagnosis of rheumatoid arthritis (2010 ACR/EULAR RA classification criteria) 2.Symptom duration =12months 3. No previous disease modifying anti-rheumatic drug (DMARD) therapy 4. Active RA at baseline (defined as: DAS28 = 3.2) 5. Active hand and/or wrist joint evaluable by US and MRI (with no planned surgery during the study period) 6. Patients without any contraindication to MRI Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1.Patients unwilling or unable to receive MTX for the duration of the study. 2.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. 3.Suspicion of diagnosis of tuberculosis: 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. 4.Intramuscular, oral 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. 5. Patients with serious infections within 3 month of enrolment (screening) or persistent infections. 6. 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). 7. Known positive serology for hepatitis B or C, or HIV
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Effective biologic drugs such as TCZ offer the opportunity of achieving disease control (remission) rapidly. There is also increasing data suggesting these newer complex biologic treatments may be able to reset the disease if used in early, untreated RA with the result that the therapies can be stopped rather than continued longterm. Finally, RA is associated with poor health outcomes and death due to early heart disease (atherosclerosis) it is unclear whether there is evidence of abnormalities in newly diagnosed RA but gaining good control of RA disease is important as this should hopefully reduce this increased risk. TCZ is usually given in combination with methotrexate (MTX; a standard treatment) but may also be given on its own. Secondary Objectives: In patients that receive TCZ either on its own or in combination with methotrexate; 1. Proportion of patients that achieve clinical remission, to answer: how rapidly can clinical remission be achieved? 2. Is there significant re;Primary end point(s): In patients with early, treatment-naive RA treated with either TCZ/MTX combination or TCZ monotherapy : • This is an exploratory study to evaluate change in expression of JAK 1-3 (as well as STAT and p38 MAPK).;Main Objective: Tocilizumab (TCZ) is an anti-IL6 receptor monoclonal antibody. IL6 is a pro-inflammatory cytokine. Dyregulated production of this cytokine is implicated in the pathogenesis of rheumatoid arthritis (RA). It signals via the activation of key proteins - Janus kinases (JAKs) and transcription factors of the STAT family. By disrupting these pathways TCZ may be able to influence key immune cells and their function with minimal to no collateral effect on other systems. Primary Objective: To determine in patients with early, treatment naive RA, how TCZ and Methotrexate (MTX) combination or TCZ monotherapy influences key signalling pathways as well as explore other mechanisms of action including p38d mitogen activated protein ( | — |
Countries
United Kingdom
Outcome results
None listed