PREVALENCE OF Anti-CCP POSITIVITY AND SUBCLINICAL SIGNS OF INFLAMMATION IN PATIENTS WITH NEW ONSET OF NON-SPECIFIC MUSCULOSKELETAL SYMPTOMS

NCT ID: NCT03267147

Last Updated: 2022-03-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 986 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-04-27
• Study Completion Date: 2022-02-15

Brief 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.

Conditions

Rheumatoid Arthritis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

antiCCP positive

Patients with a positive result in the anti-CCP quick test and positive in antiCCP ELISA will be examined by Rheumatologist for detection of RA symptoms and followed-up for 3 years or until RA diagnosis

no intervention is given

no intervention is given

Intervention Type: OTHER

no intervention is given

antiCCP negative

Patient with negative result in antiCCP quick test or negative antiCCP ELISA will be followed-up after one year (and 3 years for ELISA negative patients) with a short questionnaire if musculoskeletal symptoms are still present or if RA was diagnosed

no intervention is given

Intervention Type: OTHER

no intervention is given

Interventions

no intervention is given

no intervention is given

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• New onset of non-specific MSK symptoms, including, but not limited to, arthralgia of the hands and the large joints such as wrists, knees, and shoulders
• Written informed consent obtained prior to the initiation of any study protocol-required procedures
• General understanding of study procedure and informed consent
• Age ≥ 18 and ≤ 65 years

Exclusion Criteria

• RA diagnosed according to modified EULAR/ACR (american college of rheumatology)-criteria
• Other known arthritis
• Other known reasons for MSK symptoms, e.g. mechanical, traumatic, etc.
• MSK symptoms previously reported at another (general) practice
• Alcohol, drug or chemical abuse
• Underage or incapable patients

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Goethe University

OTHER

Sponsor Role: collaborator

Fraunhofer Institute for Translational Medicine and Pharmacology ITMP

OTHER

Sponsor Role: lead

Responsible Party

Dr. Frank Behrens

Head of clinical research department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frank Behrens, MD

Role: PRINCIPAL_INVESTIGATOR

Fraunhofer IME

Locations

CIRI

Frankfurt am Main, Hessia, Germany

Countries

Germany

Other Identifiers

TMP-1016_01

Identifier Type: -

Identifier Source: org_study_id