Page 62 - THE EVOLUTION OF EARLY ARTHRITIS AND CARDIOVASCULAR RISK Samina A. Turk
P. 62

CHAPTER 3
Some clinicians confronted with seropositive arthralgia patients will try antimalarial treatment. Apart from being a relatively nontoxic RA remedy, the rationale for this treatment comes from the experience with antimalarials in the treatment of palindromic rheumatism, a rather ill-defined syndrome of intermittently occurring peripheral arthritis. A subgroup of those patients is RF- or ACPA-positive with a tendency to develop RA(86), and this tendency was found to be markedly reduced in a retrospective survey in those taking antimalarials(87). Another retrospective study reported a marked reduction in frequency and duration of attacks in palindromic rheumatism patients taking chloroquin(88).
In conclusion, no intervention has yet showed an effect in a randomized controlled trial in the primary prevention of RA. The scarcity of data gives rise to the suggestion that it is not easy to perform clinical trials in the at-risk phase of RA, and that positive outcomes are not readily obtained. A major ethical issue with intervening pharmacologically in this phase, is that persons are exposed to potentially toxic drugs, whereas a part of the study subjects will never develop RA.
SECONDARY PREVENTION OF RA
One of the explicit goals of the 2010 ACR/EULAR criteria for RA was to facilitate the performance of trials in early RA(65), in order to make even better use of the window of opportunity in early disease. The underlying idea was that it would be easier to design a trial for patients who were classified as RA instead of as UA. Nevertheless, already before the publication of the 2010 criteria, a number of trials had been conducted with the intention to prevent the progression of early disease, mostly not classifying as RA according to the 1987 ACR criteria(62). Part of the outcome measures of these trials was a reduction of the transition of UA to RA, which means that a successful outcome could be regarded as secondary 1987 ACR criteria prevention of RA.
The results of the PROMPT study of methotrexate to prevent progression of UA to RA (1987 criteria) and its long-term follow-up showed less progression to RA, but only in ACPA positive patients and only as long as the treatment was continued(89). Other trials in early oligoarthritis or UA have noted some transient benefit from treatment with intramuscular (STIVEA trial) or intraarticular corticosteroids compared to placebo or nonsteroidal anti-inflammatory drugs(90, 91). However, the Stop Arthritis Very Early (SAVE) trial observed that the development of 1987 RA was not delayed by intramuscular glucocorticoid treatment in oligoarthritis patients(92).
Biologics have also been tested for this indication. Three months of infliximab did not prevent progression to 1987 RA after 1 year(93). Six months of abatacept slightly reduced the progression of UA to 1987 RA from 67 to 46%(94). Abatacept treatment also had an impact on radiographic and MRI inhibition, which was maintained for 6 months after treatment stopped. The STREAM study, a trial of aggressive treatment including
60



























































































   60   61   62   63   64