Optimizing Pharmacotherapy in Patients with Rheumatoid Arthritis. An Individualized Approach.

Despite the availability of different treatment options and strategies for RA patients, the response to treatment with DMARDs is still suboptimal. Strategies to optimize the pharmacological therapy of RA are therefore warranted. Two possible strategies to improve treatment outcome in RA were therefore studied in this thesis: improving adherence to DMARD-therapy and therapeutic drug monitoring of one of the biological agents: infliximab. First, improving adherence to traditional DMARDs could not only increase the effectiveness of a drug, but it could also indirectly delay the necessity of applying (more expensive) biological therapy as traditional DMARDs are more efficacious due to better adherence. In this thesis we show that, depending on the instrument used, 68% (CQR) and 60% (MARS) of the patients were adherent to DMARDs. None of the possible risk factors for non-adherence were however strongly related to adherence, implying that no general risk factor seems to be powerful enough as a possible screening tool or target for adherence-improving interventions. Research is needed on the efficacy of interventions that are tailored to individual primary reason(s) for non-adherence. Therapeutic drug monitoring (TDM) of serumlevels of anti-TNF-alpha biopharmaceuticals could be a strategy to improve efficacy of these drugs. Data derived from both rheumatology and gastro-enterology patients suggest that serum trough concentrations of (anti) infliximab, (anti)adalimumab and etanercept may be used to optimize dose regimens and prevent prolonged use of ineffective therapy. In this thesis we demonstrate that TDM of inflixmab serum trough levels could be useful in two scenarios: the prediction of 6 months response at 6 weeks, and the detection of the significant number of patients with adequate disease activity despite having nontherapeutical infliximab levels. TDM was not effective in predicting which patients benefit from dose escalatio