VIENNA, Austria—A subgroup of patients with rheumatoid arthritis (RA) appears destined to develop progressive, erosive disease despite aggressive treatment with disease-modifying antirheumatic drugs (DMARDs). Even before arthritis symptoms develop, these patients are likely to be rheumatoid factor (RF)-positive or have antibodies against cyclic citrullinated peptide (CCP). Other factors that predict erosive disease include high C-reactive protein, persistent joint swelling, and failure to achieve low disease activity with therapy, according to Klaus P. Machold, MD, of the department of rheumatology, Medical University of Vienna, in Austria. Dr. Machold's study is reported in the current issue Rheumatology.1

"RA is an aggressive disease which requires early, aggressive treatment and, despite this early treatment, if patients are not gotten to a low state of disease activity, as rapidly as possible, the disease will progress." —Martin Jan Bergman, MD.
"Since RF and anti-CCP are thought to even predate the first clinical manifestations of RA and because they are believed to be surrogates of the complex underlying pathophysiological processes, the conclusion from these data may be that there is a subgroup of RA patients who are already determined to develop erosions even before the first clinical signs of arthritis," Dr. Machold writes.

Two-thirds developed erosive disease within 3 years

The new study included 55 patients with very early RA (<e;3 months after onset of symptoms). They were followed for 3 years. All patients underwent a complete series of clinical, serological, and radiographic assessments. Their x-rays were scored according to the Larsen method. Patients were started on DMARDs or steroids between 3 and 6 months. Biologics were not yet available during the initial recruitment of participants. Some patients did receive these agents, but there were too few to draw conclusions.

Overall, 63.6% of the patients developed erosive disease during the 3-year study. The majority (74.3%) of patients had evidence of erosive disease by year 1 and 97.2% of patients developed radiographic progression by the end of year 2. Patients who first presented with RF at >50 U/mL and/or anti-CCP were most likely to develop erosions and had greater degrees of radiological progression. The persistent presence of swollen or tender joint counts and the absence of a good clinical response (assessed by failure to achieve lasting low disease activity according to established composite disease activity indices) were also predictive of radiographic progression. By contrast, outcomes were not predicted by joint counts health assessment questionnaire (HAQ) scores, visual analog scale (VAS), and acute phase reactants.

Findings strengthen call for early, aggressive treatment

The number of patients who developed erosive disease over the 3-year study "appears relatively lower when compared with the observation of others and suggests that recognizing and treating potentially destructive arthritis as early as possible may prevent the occurrence of erosive disease at least in some patients," Dr. Machold says.

"The results presented confirm what many clinicians have felt for a long time: RA is an aggressive disease that requires early, aggressive treatment and, despite this early treatment, if patients are not gotten to a low state of disease activity, as rapidly as possible, the disease will progress," summarized Martin Jan Bergman, MD, chief of rheumatology at Taylor Hospital, in Ridley Park, Pennsylvania. Dr. Bergman reviewed the study for CIAOMed.

The new study "confirms that rheumatoid factor and anti-CCP antibodies are markers of aggressive, destructive disease [and] it also confirms that it is difficult to predict, at the first visit, who is going to be the worst patient," he said.

But "rather than discouraging physicians, this should serve as a reminder of how aggressive and rapidly progressive RA can be, in some patients and, it points to the need for rapid and aggressive suppression of the disease, preferably by using some measure of disease activity."

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Reference

1. Machold KP, Stamm TA, Nell VPK, et al. Very recent onset rheumatoid arthritis: clinical and serological patient characteristics associated with radiographic progression over the first years of disease. Rheumatology. 2007;46:342-349.