[Prevention strategies in rheumatoid arthritis : From primary prevention to targeted drug interception]

The development of rheumatoid arthritis (RA) is a multistage process that often begins decades before the first joint symptoms appear. The first critical turning point is the loss of immunological tolerance [1]. Under the influence of chronic stimuli on the mucous membranes increased citrullination of proteins can occur [1]. Particularly in carriers of the shared epitope, the immune system recognizes these altered proteins as "foreign" and thereby produces anticitrullinated protein antibodies (ACPA), marking the onset of systemic autoimmunity [1, 2]. This primordial phase thus represents a potential therapeutic window of opportunity for preventive interventions [3]. In particular, smoking in conjunction with the presence of the shared epitope is associated with an up to 21-fold increased risk for ACPA-positive individuals [4, 5]. Other modifiable environmental factors such as smoking, obesity, diet and periodontitis also contribute to an increased risk of RA development, and thus represent the first key initial focus of primary prevention. In secondary prevention, recent interventional studies in high-risk individuals (ACPA/RF-positive with arthralgia) have shown mixed results: While hydroxychloroquine (STOP-RA) [8] remained ineffective, methotrexate (TREAT EARLIER) [9] was able to delay disease progression, particularly in ACPA-positive patients [9, 10]. Abatacept has so far proven to be the most promising approach (APIPPRA and ARIAA), with a significant reduction in the progression rate and lasting effects well beyond the treatment period. [11, 12].. The ARIAA long-term data also demonstrate that just 6 months of abatacept treatment delays the development of RA for up to 5 years, with IgA-ACPA-positive patients benefiting particularly [14]. Modern imaging using magnetic resonance imaging (MRI) and ultrasound enables the detection of subclinical inflammation, with tenosynovitis considered a highly sensitive early marker [15, 17]. The new EULAR/ACR risk stratification criteria enable the precise identification of high-risk individuals for prevention studies [18, 21]. The combination of lifestyle modifications and targeted drug intervention in high-risk patients could already be revolutionizing RA prevention today.