ACPA-NEGATIVE AND ACPA-POSITIVE RA-PATIENTS ACHIEVING DISEASE RESOLUTION DEMONSTRATE DISTINCT PATTERNS OF MRI-DETECTED JOINT-INFLAMMATION

Background: Sustained DMARD-free remission (SDFR), the sustained absence of clinical-synovitis after DMARD-discontinuation, is increasingly achievable in RA. However, prevalence differs significantly between ACPA-negative (40%) and ACPA-positive RA (5-10%). In addition, early-DAS-remission (DAS 4months <1.6) associates with SDFR in ACPA-negative RA but not in ACPA-positive RA. Based on these differences, we hypothesized that longitudinal patterns of local tissue-inflammation (synovitis/tenosynovitis/osteitis) might also differ between ACPA-negative and ACPA-positive RA-patients achieving SDFR. Objectives: With the ultimate aim to increase understanding of disease-resolution in RA, we studied MRI-detected joint-inflammation over time in relation to SDFR-development in ACPA-negative RA and ACPA-positive RA. Methods: 198 RA-patients (94 ACPA-negative and 104 ACPA-positive) underwent repeated MRIs (0/4/12/24-months) and were followed on SDFR-development. The course of MRI-detected total-inflammation, and synovitis/tenosynovitis/osteitis individually, were compared between RA-patients who did and did not achieve SDFR, using Poisson-mixed-models. 170 ACPA-positive RA-patients from the AVERT-1 were studied as ACPA-positive validation-population. Results: In ACPA-negative RA, patients achieving SDFR had similar baseline total inflammation-levels, which declined 2.0-times stronger in the first-year of DMARD-treatment (IRR 0.50, 95%CI;0.32-0.77, p<0.01) compared to patients without SDFR. This stronger decline was seen in tenosynovitis/synovitis/osteitis. In contrast, ACPA-positive RA-patients achieving SDFR, had already lower inflammation-levels (especially synovitis/osteitis) at disease-presentation (IRR 0.45, 95%CI;0.24-0.86, p=0.02) compared to non-SDFR patients, and remained lower during follow-up (p=0.02). Similar results were found in the ACPA-positive validation-population. Conclusion: Compared to RA-patients without disease-resolution, ACPA-positive RA-patients achieving SDFR have less severe joint-inflammation from diagnosis onwards, whilst ACPA-negative RA-patients present with similar inflammation-levels but demonstrate a stronger decline in the first year of DMARD-therapy. These different trajectories suggest that mechanisms underlying resolution of RA-chronicity in both RA-subsets might be different and indicates the relevance of the total inflammatory-load in ACPA-positive-RA. REFERENCES: [1]Verstappen M, Niemantsverdriet E, Matthijssen XME, le Cessie S, van der Helm-van Mil AHM. Early DAS response after DMARD-start increases probability of achieving sustained DMARD-free remission in rheumatoid arthritis. Arthritis Res Ther. 2020 Nov 23;22(1):276. Figure 1. Patterns of MRI-detected joint-inflammation in RA-patients achieving SDFR compared to those who did not, stratified for ACPA-status Disclosure of Interests: Marloes Verstappen: None declared, Xanthe Matthijssen: None declared, Sean Connolly Shareholder of: Dr. Sean E. Connolly, Ph.D. is a shareholder of Bristol Myers Squibb, Employee of: Dr. Sean E. Connolly, Ph.D. is an employee of Bristol Myers Squibb, Michael A Maldonado Shareholder of: Dr. M. Maldonado, Ph.D. is a shareholder of Bristol Myers Squibb, Employee of: Dr. M. Maldonado, Ph.D. is an employee of Bristol Myers Squibb, Thomas Huizinga Speakers bureau: Tom WJ Huizinga/the department of rheumatology LUMC has received research support/lecture fees/consultancy fees from Merck, UCB, Bristol Myers Squibb, Janssen, Pfizer, Novartis, Sanofi-Aventis, Galapagos, Boeringher and Eli Lilly, Consultant of: Tom WJ Huizinga/the department of rheumatology LUMC has received research support/lecture fees/consultancy fees from Merck, UCB, Bristol Myers Squibb, Janssen, Pfizer, Novartis, Sanofi-Aventis, Galapagos, Boeringher and Eli Lilly, Grant/research support from: Tom WJ Huizinga/the department of rheumatology LUMC has received research support/lecture fees/consultancy fees from Merck, UCB, Bristol Myers Squibb, Janssen, Pfizer, Novartis, Sanofi-Aventis, Galapagos, Boeringher and Eli Lilly, Annette van der Helm-van Mil: None declared Citation: , volume 81, supplement 1, year 2022, page 274Session: Rheumatoid arthritis – prognosis, predictors and outcome (Poster Tours)