Rheumatoid Arthritis Treatment After First Anti-TNF INvestiGation

Open-label, Randomized Controlled Trial Comparing Tocilizumab to Anti-TNF Treatment and Discovery of Biomarkers for Treatment Selection in Rheumatoid Arthritis Patients With Inadequate Response to a First Anti-TNF

To compare the efficacy of switching to a different molecular target (from TNF to IL6) versus cycling to a second TNF inhibitor in patients with active RA, who have not adequately responded to a previous treatment with a first anti-TNF.

New drugs for the treatment of rheumatoid arthritis (RA) with action on specific molecular target (e.g. anti-TNF) have improved the prognosis of patients with an inadequate response to conventional therapy such as methotrexate (MTX).

However, approximately 50% of patients treated with first-line anti-TNF discontinue treatment after two years due to ineffectiveness or adverse events. The second line treatment involves the use of another anti-TNF drug or switching to a different molecular target (anti-IL6, -CD20 or CTLA-4-Ig) in combination with MTX.

Inclusion Criteria:

• Age ≥18 years at the time of signing the informed consent form and either male or female.
• Diagnosis of RA according to the 1987 ACR classification criteria OR 2010 ACR/EULAR classification criteria at least 6 months prior to screening.
• Patients with persistent RA disease activity whilst being treated with an initial TNFi agent on a background MTX up to 20-25 mg/week for at least 12 weeks defined according to SIR and EULAR guidelines as: primary non-response: failing to improve DAS28 by ≥ 1.2 or failing to achieve DAS28 ≤ 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 ≥ 1.2.
• Methotrexate (MTX) dose stable for 28 days prior to screening.
• Patients on NSAIDs and / or corticosteroids must remain on an unchanged regimen for at least 28 days prior to study drug administration.
• The patient must be able to comply with the study visit schedule and other protocol requirements.
• The patient understands the purpose of the study and is able and willing to sign the informed consent form, according to ICH/GCP.
• Signed written informed consent for biological analysis.
• Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to start of trial. Women of childbearing potential and male patients must be willing to practice acceptable methods of contraception during treatment and for 6 months (female patients) and 3 months (male patients) after discontinuation of treatment.

Exclusion Criteria:

• Patients who have previously received more than 1 TNFi drug OR any other biological therapy.
• Patients with inflammatory joint disease of different origin or any arthritis with onset prior to 16 years of age.
• Patients taking any disease-modifying antirheumatic drug (DMARDs) (e.g. all except methotrexate). Discontinuation must occur at least 28 days prior to study treatment start.
• History or presence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug.
• Known hypersensitivity to any active substance or excipients of study drug.
• Pregnancy or breast feeding.