Ultrasound as Imaging Biomarker of Early Response to Tocilizumab and Methotrexate in Very Early Rheumatoid Arthritis

Inclusion Criteria: * Diagnosis of RA fulfilling the 2010 EULAR/ACR (European League Against Rheumatism/ American College of Rheumatology classification criteria) * Disease duration no longer than 12 months from the time of first swollen joint and no longer than 12 months from the time of initial diagnosis * Age : 18-75 years * Disease activity defined by a disease activity score DAS28-CRP \> 3.2 or all must be met: tender joint count (TJC) of ≥4 and swollen joint count (SJC) ≥4 * US SH or PD synovitis scores \>1 for at least 2 joints (MCP:2-5 or PIP:2-5 or CMC:2-5 or wrist joints or MTP:2-5 or ankle joints) and US SH or PD synovitis scores ≥1 for at least 1 other joint (MCP:2-5 or PIP:2-5 or or CMC:2-5 or wrist joints) * Naïve to DMARDs (methotrexate, leflunomide, sulphasalazine) and naïve to any biologics or biosimilars. Exclusion Criteria: * History of other concomitant autoimmune disease such as lupus or psoriatic arthritis * Meeting diagnostic criteria for any other rheumatic disease than RA (e.g. gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis, psoriatic arthritis, arthropathy or inflammatory bowel disease) * Any previous treatment with : 1. Biologics: Etanercept, infliximab, certolizumab, golimumab, abatacept, adalimumab, anakinra, tocilizumab, tofacitinib, etc. 2. Any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti- CD3, anti-CD19 and anti-CD20 3. Intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline. 4. Alkylating agents such as chlorambucil, or with total lymphoid irradiation * Previous MCP arthroplasty or wrist arthrodesis. Participants who have undergone or are scheduled to undergo joint arthroplasties other than the MCP joints can be recruited in the study provided all other eligibility criteria are met. * Current liver disease requiring medication * Current symptoms of severe progressive or uncontrolled renal, hematologic, gastro-intestinal, pulmonary, cardiac, neurologic or cerebral disease whether or not related to rheumatoid arthritis, that would jeopardize inclusion in the protocol as judged by the clinician * History of malignancy or lymphoproliferative disease, within the last 5 years, with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma in situ of cervix which that has been fully excised/cured with no evidence of recurrence * Concomitant diagnosis or history of diverticulitis, peptic ulcer disease, diverticulosis requiring antibiotic treatment or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations * Evidence of active or latent bacterial, viral, fungal (except for fungal infections of nail beds), mycobacterial or other opportunistic infections at the time of potential enrolment * Any major episode of infection requiring hospitalisation or treatment with IV antibiotics within 4 weeks or oral antibiotics within 2 weeks of screening' * Herpes zoster or cytomegalovirus infection that resolved less than 2 months before the informed consent was signed * Subjects at risk of tuberculosis (TB) are excluded if any of the following is present: * A history of active TB within the last 3 years, even if treated Latent TB that was not successfully treated ≥ 4 weeks Current clinical radiographic, or laboratory evidence of active TB * Subjects who received live vaccines within 4 weeks of the anticipated first dose of study medication. Live and live attenuated vaccines should not be given concurrently * Subjects must agree not to take live attenuated vaccines (including seasonal nasal flu vaccine, varicella vaccine for shingles or chickenpox, MMR or MMRV, oral polio vaccine and vaccines for yellow fever, measles, mumps or rubella) thirty (30) days before the Screening Visit, throughout the duration of the trial and for sixty (60) days following the subject's last dose of study drug * Subjects with positive test results for hepatitis B surface antigen or hepatitis C, or HIV detected with polymerase chain reaction or immunoblot assay * Subjects with primary or secondary immunodeficiency * History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies * Major surgery within 8 weeks * Patients with lack of peripheral venous access * Pregnancy or breast-feeding * Females of childbearing potential can only participate if using reliable contraception * Intra-articular steroid injection in the joints assessed by US less than four weeks before screening * Anticipated non-compliance with the protocol Laboratory exclusion criteria * Platelet count \<100 x 109/l (100,000/mm3) * Haemoglobin \<85 g/l (8.5 g/dl; 5.3 mmol/l) (\<8.0) * White Blood Cells \<3.0 x 109/l (3000/mm3) or \>14,000/μl * Absolute Neutrophil Count \<2.0 x 109/l (2000/mm3) * Absolute Lymphocyte Count \<0.5 x 109/l (500/mm3) * Positive Hepatitis BsAg, or Hepatitis C antibody * Serum creatinine \>1.4 mg/dl (124 μmol/l) in female patients and \>1.6 mg/dl (141 μmol/l) in male patients. Patients with serum creatinine values exceeding limits may be eligible if their GFR is \>30 * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>1.5 times upper limit of normal (ULN) * Total Bilirubin \> ULN