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Using Reference Reagents to Confirm Robustness of Cytokine Release Assays for the Prediction of Monoclonal Antibody Safety
Published on: September 15, 2023
Primary care anti-cyclic citrullinated protein antibody testing for rheumatoid arthritis and accompanying pathway
George F G Allen1,2, Timothy J McDonald1,2, Stuart Kyle3
1NIHR Exeter Biomedical Research Centre, University of Exeter, Exeter, UK.
Objectives:
Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies are alternative diagnostic tests for RA with similar sensitivity. Anti-CCP antibodies have improved specificity compared with RF and so should result in fewer false positives. A retrospective, observational study was conducted following a change in the primary care pathway and test for inflammatory arthritis from RF to anti-CCP antibodies, assessing real-world impact on referrals.
Methods:
The primary care test was changed from RF to anti-CCP antibodies as part of a service development in East and North Devon, UK (population 463 000). Data were monitored post-implementation from 1 March to 31 August 2024. Anti-CCP antibody testing was made available to primary care. General practitioner order communications automatically redirected requests for RF to anti-CCP antibodies. Local referral guidelines were implemented recommending anti-CCP antibodies to support referral decisions but not for rule-out of inflammatory arthritis. The equivalent 6-month period from 2023 when RF was the primary test for inflammatory arthritis was used for comparison.
Results:
Positive tests decreased from 10.6% with RF to 3.9% with anti-CCP antibodies. This led to 57 (39%) fewer referrals following a positive test. The false positive rate among those referred to rheumatology decreased from 59% (91/148) with RF to 32% (29/91) with anti-CCP antibodies. Anti-CCP antibodies and RF detected similar numbers of inflammatory arthritis cases with a case yield of 2.1% for both tests.
Conclusion:
Replacement of RF with anti-CCP antibodies within a redesigned inflammatory arthritis pathway reduced unnecessary rheumatology referrals. This could help oversubscribed services reduce waiting times and thus contribute to timely diagnosis of inflammatory arthritis.
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