Abstract
IntroductionThe utility of reassessing anti-cyclic citrullinated peptide (anti-CCP) antibody status later in disease in patients presenting with early undifferentiated inflammatory polyarthritis, particularly in those who test negative for both anti-CCP and rheumatoid factor (RF) at baseline, remains unclear. We aimed therefore to determine the stability of CCP antibody status over time and the prognostic utility of repeated testing in subjects with early inflammatory polyarthritis (IP).MethodsAnti-CCP and RF were measured at baseline and 5 years in 640 IP patients from the Norfolk Arthritis Register, a primary care-based inception cohort. The relation between change in anti-CCP status/titer and the presence of radiologic erosions, the extent of the Larsen score, and Health Assessment Questionnaire (HAQ) score by 5 years was investigated.ResultsWith a cut-off of 5 U/ml, 28% subjects tested positive for anti-CCP antibodies, 29% for RF, and 21% for both at baseline. Nine (2%) anti-CCP-negative patients seroconverted to positive, and nine (4.6%) anti-CCP-positive individuals became negative between baseline and 5 years. In contrast, RF status changed in 17% of subjects. However, change in RF status was strongly linked to baseline anti-CCP status and was not independently associated with outcome. Ever positivity for anti-CCP antibodies by 5 years did not improve prediction of radiographic damage compared with baseline status alone (accuracy, 75% versus 74%). A higher baseline anti-CCP titer (but not change in anti-CCP titer) predicted worse radiologic damage at 5 years (P < 0.0001), even at levels below the cut-off for anti-CCP positivity. Thus, a titer of 2 to 5 U/ml was strongly associated with erosions by 5 years (odds ratio, 3.6 (1.5 to 8.3); P = 0.003).ConclusionsRepeated testing of anti-CCP antibodies or RF in patients with IP does not improve prognostic value and should not be recommended in routine clinical practice.
Highlights
The utility of reassessing anti-cyclic citrullinated peptide antibody status later in disease in patients presenting with early undifferentiated inflammatory polyarthritis, in those who test negative for both anti-CCP and rheumatoid factor (RF) at baseline, remains unclear
Baseline cohort characteristics Between 1990 and 1994, 1,098 subjects were recruited to Norfolk Arthritis Register (NOAR)
Consistent with previous studies, RF status was more likely to change over time, with a lower proportion of subjects testing positive for RF at 5 years than at presentation [15,16]
Summary
The utility of reassessing anti-cyclic citrullinated peptide (anti-CCP) antibody status later in disease in patients presenting with early undifferentiated inflammatory polyarthritis, in those who test negative for both anti-CCP and rheumatoid factor (RF) at baseline, remains unclear. We aimed to determine the stability of CCP antibody status over time and the prognostic utility of repeated testing in subjects with early inflammatory polyarthritis (IP). The use of biomarkers to distinguish those patients with inflammatory polyarthritis (IP) who will progress testing alone, and evidence regarding the value of repeated testing is lacking [2,3,6]. It is not uncommon in clinical practice for both anti-CCP and RF to be tested on multiple occasions in an individual patient [10]. What is the likelihood that anti-CCP antibody levels will change over the course of disease in patients with IP? Second, does a change in anti-CCP antibody status or titer associate with disease-severity outcomes and, if so, would a lower threshold improve prediction of adverse outcomes?
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