Maxime Verhoeven

10 Chapter 1 GENERAL INTRODUCTION Rheumatoid arthritis (RA) is a relatively common systemic inflammatory disease, which is characterized by chronic inflammation of the synovial membrane. 1 This can result in joint damage, declined physical function and reduced quality of life. 2 The prevalence is about 1-2% in Dutch adults and it more often affects females. 3 The disease has a high socio-economic impact as RA patients may be limited in their daily functioning due to disease-related stiffness, fatigue and/or pain, which may result in absence from (paid) work due to sick leave. In addition, presenteeism (i.e., being at work but working less efficiently) is observed more often in RA patients, compared to in healthy persons of the same age. 4 In 2017, approximately 0.75% of all health care costs in the Netherlands (i.e., 654 million euro) was spent on healthcare for RA patients. 5 To optimally treat RA patients, it is essential to reduce disease activity as soon after diagnosis as possible, preferably within the ‘window of opportunity’. 6 This refers to a time period starting at the onset of symptoms, and lasting presumably 3-6 months, in which initiation of treatment might result in improved disease related outcomes on the longer-term, due to prevention of irreversible joint damage, that may fuel disease activity. 7,8 For instance, drug free remission is achieved in more patients starting treatment (very) early. 7 In this, the optimal treatment should be based on shared decision making between patient and rheumatologist, taking factors like disease activity, progression of structural joint damage, safety aspects, comorbidities, personal circumstances, quality of life and cost into account. 2 Medical treatment with disease modifying anti-rheumatic drugs (DMARDs) targets inflammation, and is associated with improved physical functioning and inhibition of progression of structural joint damage. Conventional synthetic (cs), biologic (b), and target synthetic (ts) DMARDs are used in RA patients. 1 Generally treatment with a single csDMARD, mostly methotrexate (MTX), is started directly after diagnosis according to international guidelines. 2,9 Since it will take MTX therapy several weeks exert its full effect, it may be combined with short-term use of glucocorticoids (GCs) that are immediately effective, to ‘bridge’ the lag-time of csDMARD to become fully effective. 2 If the treatment target is not achieved within 3-6 months and poor prognostic factors (e.g., joint damage or high number of swollen joints) are present, the treatment strategy will have to be intensified. 2,9 In that case, another csDMARD, a bDMARD (e.g., TNF-inhibitors) or a tsDMARD (e.g., small molecules such as JAK-inhibitors) can be added (i.e., more intensive treatment strategy). The bDMARDs are produced using live cell systems, and categorized based on their specific mechanism of action. bDMARDs and the recently introduced tsDMARDs are considered highly effective, but significantly more expensive compared to csDMARDs.