 - Inadequate response on earlier optimal use of a minimum of two DMARDs disease modifying anti-rheumatic drugs such as goldsalts, salazopyrine, leflunomide, methotrexate MTX as far as one of the two used DMARDs is MTX that at the exception of a documented intolerance despite the association with folic acid, should have been administered IM or oral during a minimum of 3 months and at a minimal dose of 15mgweek. 