The Evidence for Early Intervention

When does rheumatoid arthritis start?

Immunologic events in RA occur many years before the onset of clinical disease. Rheumatoid factor has been shown in patients years before the onset of symptoms [3]. Similarly, anti–cyclic citrullinated peptide antibodies precede disease by 14 years and precede the detection of rheumatoid factor by an average of 2.8 years [4]. Increases in highly sensitive C-reactive protein (CRP) have been shown before onset of clinical disease in patients with or without serologic abnormalities [5]. When

Are rheumatoid arthritis classification criteria useful?

The American College of Rheumatology (ACR) classification criteria for RA were developed to improve homogeneity of patients entered into clinical trials with established disease [12]. It is erroneous to use the criteria for the purpose of diagnosis, especially in the early stages. Patients who satisfy 1987 ACR classification criteria for RA, with very short disease duration, can have a qualitative change in their outcome when treated at presentation, with 50% remission rates after a single dose

What is the importance of early disease?

It already has been established that disease may predate symptoms by many years. For the purposes of clinical trials in early RA, symptom duration of less than 2 years has been the convention, with a shift toward 12 months in recent years. This duration was chosen because, at the end of this period, most patients have incurred significant damage when treated conventionally. Also no prior disease-modifying antirheumatic drug (DMARD) therapy or corticosteroid use is deemed appropriate for optimal

What is the evidence to support early intervention?

The level of CRP is used as a surrogate marker of inflammation and progression of radiographic damage [29], [30], [31]; loss of function and bone mineral density correlates well with persistent elevation of the CRP. Suppression of CRP results in at least stabilization of the respective parameters [17], [18], [32], [33]. This situation reinforces the paradigm: inflammation × time = damage [34].

From longitudinal MRI studies in early RA, synovitis seems to precede bone edema and subsequent

Is disease-modifying antirheumatic drug treatment more toxic?

In practical terms, 90% of patients diagnosed with RA are treated with DMARDs within 3 years of diagnosis [1]; most patients eventually are subjected to potential DMARD toxicity. NSAIDs have been compared with DMARDs by calculating a toxicity index derived from symptoms, abnormal laboratory measures, and hospitalizations related to treatment [41], [42]. The comparisons show that some commonly used NSAIDs have toxicity indices considerably greater than intramuscular gold and hydroxychloroquine

Published studies in early rheumatic arthritis

There are no meta-analyses of therapy in early RA. Trials selected here for review study only patients with disease duration less than 2 years.

New therapies

Tumor necrosis factor (TNF)-α–blocking agents are now available. Studies in early disease are emerging. In a study of 632 patients with active early RA (<3 years), etanercept showed a significant improvement in clinical outcome when measured using ACR improvement area under the curve, but failed to reach significance when the more accepted and conventional ACR improvement criteria were used versus methotrexate over 12 months [74]. There was a significant reduction in erosion score for the

Discussion

The benefit of early treatment in RA is supported by published data. Properly conducted studies, with most currently used DMARDs, show clinical improvement and retardation of radiographic damage, although evidence suggests x-ray changes are insensitive and lag considerably behind inflammatory activity [14]. Studies using newer techniques of joint assessment, such as MRI and ultrasound, have shown greater sensitivity and a close temporal correlation with inflammatory activity and damage