Tight control and long-term prediction in rheumatoid arthritis

Abstract

Treatment of patients with rheumatoid arthritis (RA) has changed significantly in the past decades with regard to the use of treatment strategies as well as to set the aim of treatment. Research evaluated strategies to reach the aim of remission or low disease activity instead of clinically relevant improvement. These strategies can be grouped as ‘tight control’, which is evaluated in this thesis. Tight control can be defined as a treatment strategy with dose and strategy adjustments tailored to the disease activity of each individual RA patient aimed at a predefined level (i.e. ‘treat to target’) of low disease activity or preferably remission within a reasonable period of time. In the thesis aspects of tight control are described, including effectiveness, adverse effects, and long-term outcome, while also research into possible predictors of RA to prevent under- and overtreatment of the individual RA patient is described. This thesis shows that tight control is effective, especially in case of adding low-dose prednisone to a methotrexate (MTX) based tight control strategy (i.e. CAMERA-II trial). Within the tight control strategies relatively mild adverse events were observed; weighing efficacy and toxicity of the strategy, efficacy clearly outweighs toxicity. Tight control can be obtained with several different treatment strategies. When a patient does not sufficiently response to (oral) MTX treatment as next treatment strategy step, switching from oral to subcutaneous MTX seems to be effective, in contrast to adding cyclosporine to MTX. Also, it is important to decide at which moment early in the treatment of RA, medication should be added to the strategy. This decision can be based upon the response to treatment after 6 months after start of treatment, and possibly even earlier. Tight control as treatment strategy probably needs to be continued also for a prolonged period of time, especially for RA patients with moderate to high disease activity. To treat to target, assessment of this target, e.g. remission should be validated. This thesis shows that the use of DAS28 (a disease activity score not including the feet) as a monitoring instrument for the individual patient is not always straightforward. Also the presence of tender points influences disease activity state as calculated by the DAS28 and therefore use of this index for tight control can lead to undertreatment of RA patients. Disease activity states as assessed with these indices should be interpreted with caution, especially low or remission disease activity states. For an optimal choice regarding tight control strategies good predictors are needed to predict the outcome of each individual RA patient. Prediction of the most optimal individual dose of MTX with clinical variables and prediction of disease activity and radiographic outcome with biomarkers was explored within the thesis, but these preliminary results needs to be further evaluated