Page 61 - THE EVOLUTION OF EARLY ARTHRITIS AND CARDIOVASCULAR RISK Samina A. Turk

HOW DOES ESTABLISHED RHEUMATOID ARTHRITIS DEVELOP
chronicity of inflammation. One of these could be the total burden of inflammation,
which builds up in the early clinical phase. It is conceivable that once a critical mass of inflammatory tissue has been reached, it is no longer possible to control it effectively.
This theory is difficult to test, as there is no technique available at present, which can 3 reliably test the total load of inflammatory tissue in a person.
PRIMARY PREVENTION OF RA
The different stages of RA development offer opportunities for preventive interventions, varying from (primary) prevention of the development of arthritis in the at-risk phase to (secondary) prevention of progression from UA to RA or from early to established RA.
The list of risk factors for RA (Table 2) shows that there are several opportunities for lifestyle changes to help prevent RA. Smoking is the strongest environmental risk factor for RA, in particular for ACPA-positive RA, and it has been calculated in Denmark and Sweden that population-wide cessation of smoking would result in more than one-third less cases of ACPA positive RA(81, 82). Other potentially modifiable factors include dietary changes, weight reduction and dental care to reduce periodontitis. These are currently being addressed in the PRE-RA Family Study Boston, which is exploring the attitudes of family members of RA patients toward a lifestyle intervention based on a genetic plus environmental risk assessment(83). Participants are randomized to receive feedback and education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics, and biomarkers or to receive standard RA information. Four behavioral RA risk factors are included in the risk estimate: smoking, excess body weight, poor oral health, and low fish intake. The trial outcomes will be changes in willingness to alter behaviors. As we learn more about these relations, such information programs can be refined. At present, the most important advice is for family members of ACPA-positive RA patients, to refrain from smoking(82).
The concept of primary prevention of RA with drugs has become possible through the recognition of a prolonged at-risk phase with variable symptoms and/or autoimmunity before the outbreak of clinical RA. The first clinical trial was a post hoc analysis of the effect of vitamin E in a study designed to prevent coronary heart disease in the general population(84). Although the trial was negative the for prevention of both heart disease and RA, there was a trend toward protection against RF-positive RA. The next study was a trial of two intramuscular injections of 100 mg dexamethasone or placebo in ACPA and/or RF-positive arthralgia patients(85). Furthermore, this trial did not affect the onset of arthritis, although autoantibody levels were suppressed for 6 months. Meanwhile, trials of rituximab (Prevention of RA by B cell-directed therapy (PRAIRI) trial, NTR1969; www.trialregister.nl), of abatacept (Arthritis Prevention In the Pre-clinical Phase of Rheumatoid Arthritis (APIPPRA) trial; www.isrctn.com/ISRCTN46017566) and of atorvastatin (STAtins in the Prevention of RA (STAPRA) trial; NTR5265; www. trialregister.nl) in the same patient category are ongoing.
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