P239 Third generation APCA improve prediction of clinical arthritis in at-risk individuals with positive second generation ACPA

Background Anti-citrullinated peptide antibodies (ACPA) are important biomarkers in rheumatoid arthritis (RA) and can predict arthritis development in at-risk individuals. ACPA are conventionally detected using the second-generation or third generation IgG anti-CCP antibody (Ab) assays. Although the value of anti-CCP2 Ab for predicting progression to RA in at-risk individuals is well understood, very little knowledge exists for anti-CCP3.The objectives of this study were: i) To evaluate the prevalence of serum anti-CCP3 Ab in serum anti-CCP2 Ab positive at-risk individuals (CCP2+ at-risk); ii)) To study the incremental value of anti-CCP3 Ab in CCP2+ at-risk subjects for predicting progression to clinical inflammatory arthritis (IA). Methods Anti-CCP3 Ab were tested on stored serum samples obtained from 347 CCP2 + (BioRad, USA) at-risk individuals from the Leeds CCP study. Anti-CCP2 and anti-CCP3 tests positivity threshold was >2.99 IU/ml and >20 units, respectively. Moreover, anti-CCP2 and anti-CCP3 titres were categorised according to manufacturer’s cut-off: low (LT) and high (HT) for anti-CCP2, negative/weak/moderate/strong for anti-CCP3. Progression to IA was defined as the development of clinical synovitis in at least one joint. Only subjects with at least one follow-up visit were included in the progression analysis (n = 317). Results Anti-CCP3 Ab were negative in 138/347 (39.7%) CCP2+ individuals, and weakly, moderately, and strongly positive in 15/347 (4.3%), 5/347 (1.4%) and 189/347 (54.4%) individuals, respectively. LT and HT anti-CCP2 Ab were found in 103/347 (29.7%) and in 244/347 (70.3%) individuals, respectively. Eighty-eight/317 subjects (28%) developed IA. The rate of progression of LT and HT anti-CCP2, when anti-CCP3 was negative, decreased from 6.5% to 2.7%, and from 36.6% to 9.4%, respectively. Progression in anti-CCP2 HT increased from 36.6% to 45.6% when anti-CCP3 was positive (Table 1). Conclusion Our results support an important role for anti-CCP3 Ab in improving prediction of IA in CCP2+ at-risk individuals. Disclosures A. Di Matteo None. K. Mankia None. L. Duquenne None. M. Mahler Other; Inova Diagnostic. D. Corscadden None. K. Mbara None. L. Garcia-Montoya None. J. Nam None. P. Emery Honoraria; AbbVie, BMS, Bristol-Myers Squibb, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Samsung, Samsung Bioepis Co., Ltd.