Inclusion Criteria:

Patients meeting all of the following criteria will be considered for enrolment into the
study:

1. Age equal to or greater than 18 years at the time of signing the Informed Consent
Form and either male or female.

2. Men and women of child bearing potential (WCBP) (Appendix 1) must use at least one
effective birth control measure (Appendix 2) for the duration of study and should
continue such precautions for 6 months after receiving the last dose of protocol
treatment.

3. Patients with a diagnosis of rheumatoid arthritis (1987 revised ACR criteria)
confirmed at least 6 months prior to screening.

4. Patients who have exhausted conventional DMARD options (including MTX).

5. Patients with persistent RA disease activity whilst being treated with an initial
TNFi agent for at least 12 weeks defined as*:

- Primary non-response: failing to improve DAS28 by equal to or greater than 1.2
or failing to achieve DAS28 equal to or less than 3.2 within the first three to
six months of starting the initial TNFi.

- Secondary non-response: determined by physician decision with evidence of flare
and deterioration in DAS28 of equal to or greater than 1.2 (having previously
demonstrated a response to the TNFi).

- These criteria are consistent with BSR guidelines.

6. MTX dose stable for 28 days prior to screening and to be continued for the duration
of the study.

7. Patients on NSAIDs and / or corticosteroids must remain on an unchanged regimen for
at least 28 days prior to study drug administration.

8. The patient must be able to comply with the study visit schedule and other protocol
requirements.

9. The patient understands the objectives of the study and is able and willing to sign
the Informed Consent Form.

Exclusion Criteria:

Patients will be excluded from this study for any of the following reasons:

1. Patients who have previously received more than 1 TNFi drug OR any other biological
therapy.

2. Patients with inflammatory joint disease of different origin, mixed connective tissue
disease, Reiter's syndrome, psoriatic arthritis, systemic lupus erythematosus, or any
arthritis with onset prior to 16 years of age.

3. Patients with other co-morbidity: examples include uncontrolled diabetes,
uncontrolled hypertension, unstable ischaemic heart disease, active bowel disease,
active peptic ulcer disease, recent stroke (within three month before study entry
(screening)), or other condition which, in the opinion of the investigator, would put
the patient at risk to participate in the study or would make implementation of the
protocol difficult.

4. Patients with known significantly impaired bone marrow function as for example
significant anaemia, leukopenia, neutropenia or thrombocytopenia as shown by the
following laboratory values :

- Haemoglobin less than 8.5 g/dl

- Hematocrit less than 30%

- Platelet count less than 100 x 109 / L

- White blood cell count less than 3.5 x 109 / L

- Neutrophils count less than 1 x 109 / L

5. Patients with known severe hypoproteinaemia, e.g. in nephrotic syndrome or impaired
renal function, as shown by:

- Serum Creatinine greater than 150 umol / L

- Creatinine Clearance 50 ml/min

6. Patients unable or unwilling to stop treatment with a prohibited DMARD (e.g. oral or
injectable gold, chloroquine, hydroxychloroquine, cyclosporine, azathioprine,
leflunomide, sulphasalazine) at least 28 days prior to study drug administration
(week 0).

7. Patients unable or unwilling to stop treatment with etanercept at least 4 weeks prior
to study drug administration (week 0); or infliximab, adalimumab and certolizumab 8
weeks prior to study drug administration (week 0).

8. Patients receiving doses of prednisolone greater than 10mg/day within the previous 28
days before study drug administration (week 0).

9. Patients receiving intra-articular or intra-muscular steroid injections within 28
days before screening.

10. Scheduled or anticipated surgery (particularly surgery to the involved knee joint
within the study period).

11. Treatment with any investigational drug in the last 90 days before study drug
administration (week 0).

12. Pregnancy, lactation or women of child-bearing potential (WCBP) unwilling to use an
effective birth control measure (Appendix 2) whilst receiving treatment and for 6
months after the last dose of protocol treatment.

13. Men whose partners are of child-bearing potential but who are unwilling to use an
effective birth control measure (Appendix 2) whilst receiving treatment and for 6
months after the last dose of protocol treatment.