PREVALENCE OF Anti-CCP POSITIVITY AND SUBCLINICAL SIGNS OF INFLAMMATION IN PATIENTS WITH NEW ONSET OF NON-SPECIFIC MUSCULOSKELETAL SYMPTOMS
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid; Inflammation
Study type: Observational

Summary: 
      Non-interventional, prospective, observational study to assess the relative risk of anti-CCP
      positive patients to develop (subclinical) signs of inflammation in accordance with early
      Rheumatoid Arthritis (RA) in a population without pre-classified RA but new1 onset of
      non-specific musculoskeletal (MSK) symptoms in general practices in Germany and subsequent 36
      months follow-up by rheumatologists
    

Detailed description: 
      Studies of early arthritis cohorts have shown that a large number of early arthritis patients
      cannot be accurately diagnosed at their first visit, and hence are often referred as
      undifferentiated arthritis patients. If patients are found to be anti-CCP(+) when referred to
      the clinician, however, more than 90% develop RA within 3 years - in contrast to only 30% of
      the anti-CCP(-) patients. The presence of anti-CCP antibodies in undifferentiated arthritis
      therefore accurately predicts development of RA. Anti-CCP antibodies are very specific for
      RA, and they are produced at significant level very early in disease. The specificity of
      anti-CCP antibodies for the diagnosis of RA is high (94.1-99.0%). Moreover, it has been
      reported that anti-CCP antibodies can be present many years before the first visit to the
      clinic (up to 18 years). Furthermore, the presence of anti-CCP antibodies at the first visit
      to the clinician predicts radiographic progression, as demonstrated by many studies that have
      shown a strong association of anti-CCP positivity with the development of bone erosions.Early
      diagnosis of RA coupled with rational use of disease-modifying anti-rheumatic drugs (DMARD)
      has been shown to have a favourable effect on the course of the disease. Early and accurate
      diagnosis has therefore become increasingly important. Implementing anti-CCP quick tests in
      general practices could facilitate an early detection of RA or the allocation to a high risk
      RA group. This, in turn, would guarantee an early referral of the patient to a rheumatologist
      and together with other clinical examinations can aid in the early diagnosis and treatment.
      As has been shown in many studies an early intervention is vital to preserve joint function
      and to improve patient care. In this study, we want to assess the relative risk for patients
      derived from GPs in Germany with new onset of non-specific MSK symptoms and anti-CCP test
      positivity to develop (subclinical) signs of inflammation in accordance with early RA. Those
      patients will be identified in general practices and will be tested for anti-CCP status.
      Anti-CCP positive patients will then be introduced to a rheumatologist to validate anti-CCP
      status and examine presence of clinical signs of early RA in addition to subclinical signs of
      MSK inflammation. Furthermore, to focus on the possibility of early detection of anti-CCP
      before the onset of clinically active arthritis, patients will be followed-up by a
      rheumatologist until detection of early RA or up to 36 months in total. Early RA will be
      examined using standard of care for signs of inflammation including clinical examination for
      swollen and tender joints. In addition, ultrasound will be performed to assess joint
      inflammation as well as fluorescence optical imaging technique (Xiralite®) to sensitively
      illustrate changes in microvascularisation as a marker of subclinical inflammation. In cases
      of RA diagnosis, the study ends with the date of diagnosis and patients will receive
      treatment according to local guidelines earlier and medical care will be continued in
      clinical routine care conditions outside of the study. Moreover, the cooperation status
      between GPs and rheumatologists will be evaluated using qualitative interviews. Feasibility
      of the diagnosis of early RA in at risk patients as well as the feasibility of the
      transferral of these patients from the general practice to the rheumatologist will be
      assessed. Training of GPs for detection of early RA will be improved. Overall, the hypothesis
      of the study is that patients with new onset of unspecific MSK-symptoms and who are positive
      for anti-CCP, which both are risk factors for developing RA, will be earlier introduced to
      and monitored by a rheumatologist for proper clinical examination and potential treatment
      when establishing RA, which in turn will not only improve patient care, disease outcomes and
      quality of life, but might also be cost effective.
    

Intervention name(s): no intervention is given
Intervention type(s): Other
Intervention description(s): no intervention is given
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        population without pre-classified RA but new onset of non-specific musculoskeletal (MSK)
        symptoms
      
Biospecimen description: 
      blood samples
    
Keywords: Anti-CCP; rheumatoid arthritis