A multi-center, randomized, double blind, placebo controlled study to evaluate remission in DMARD and biological naïve early reumatoid arthritis (RA) subjects treated with tocilizumab (TCZ) plus tight control methotrexate (MTX) treatment, TCZ monotherapy or tight control MTX monotherapy.

INTERVENTION:

Trade Name: RoActemra Pharmaceutical Form: Concentrate for solution for infusion Pharmaceutical form of the placebo: Concentrate for solution for infusion Route of administration of the placebo: Intravenous use Trade Name: Methotrexate 'Lederle' 2,5mg tablets Pharmaceutical Form: Tablet Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use

CONDITION:

Rheumatoid Arthritis ; MedDRA version: 15.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders

INCLUSION CRITERIA:

1. Male or non‐pregnant, non‐nursing female 2. = 18 years of age 3. Early RA (disease symptoms <1 year) according to the revised 1987 ACR and/or ACR/EULAR classification criteria of 2010 for RA 4. Disease activity measured by DAS28 = 2,6 5. Patients able and willing to give written informed consent and comply with the requirements of the study protocol 6. Immunization status current for pneumovax, influenza as assessed according to standard of care for RA patients receiving a biological agent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range

PRIMARY OUTCOME:

Main Objective: To compare the number of patients with early RA who achieve sustained remission with three different regimens: tocilizumab combined with tightly controlled MTX, tightly controlled MTX as monotherapy and tocilizumab as monotherapy. The main focus is the contrast between the combination therapy and the MTX monotherapy followed by the contrast between the two monotherapy treatments. Primary end point(s): Primary endpoint of the present study is the sustained remission rate (SRR), i.e. the proportion of patients with early RA who achieve sustained remission.; In individual patients, sustained remission is considered to be achieved if an uninterrupted period of approximately 6 months (at least 23 weeks) can be identified, over which: ; •At least 6 DAS28 values are available, including one at the beginning and one at the end of the period; •All values are <2.6, with the exception of up to 2 values which can be between 2.6 and 3.2 provided that the investigator considers the patient to be in clinical remission for RA and documents the reason for the RA‐unrelated elevation of DAS28 (such as an infection); Secondary Objective: To compare the progression of radiographic characteristics of joint damage among the three treatment strategies by use of the change in SharpvanderHeijde score.; ; To compare clinical efficacy between the three treatment strategies by use of the ACR and EULAR response criteria.; ; To study safety in the context of the three treatment strategies, including the: ; ‐ occurrence of serious adverse events leading to withdrawal. ; ‐ occurrence of serious infections ; ‐ number of patients who are unable to use adequate dosage of MTX due to increase of liver enzymes ; ; To study differences in changes in functional disability, fatigue, quality of life and cost effectiveness in the three treatment strategy groups by use of the: Dutch consensus HAQ, the FACIT‐fatigue, the IPQR, the SF‐36, VAS pain and general wellbeing Questionnaires, a Dutch Healthcare resource use and work participation questionnaire, and the EuroQol (EQ5D) questionnaire. ;