Background/Purpose: Flares of immune-mediated inflammatory diseases, as Rheumatoid Arthritis (RA) occur unpredictably representing a major burden for patients and clinicians. We aimed to dissect the synovial tissue (ST) features of RA in sustained remission that could predict disease flare once biological treatment is tapered or discontinued.

Methods: 48 RA patients in sustained clinical (DAS<1.6 for at least 9 months) and ultrasound (US) remission (Power Doppler negative) under biological-Disease Modifying Anti-Rheumatic Drug (bDMARD) plus Methotrexate underwent ultrasound guided ST biopsy. ST CD68⁺, CD21⁺, CD3⁺, CD20⁺, CD31⁺cells and collagen were assessed using immunohistochemistry and Goldner’s Trichrome staining, respectively. Some ST samples were digested with liberase and ST macrophages were sorted by FACS-ARIAIII and phenotyped. This included evaluation of the number of CD206 positive and negative anti-inflammatory and pro-inflammatory macrophages, respectively. After study entry, RA were randomly assigned to tapering/discontinuation group (TAP/DISC: tapering for 6 months first and discontinuing bDMARD afterwards) or to the group maintaining the same therapeutic scheme (CONT). Each RA was followed every 3 months to assess the occurrence of disease flare after treatment change for at least 6 months.

Results: At study entry, 29 RA were assigned to TAP/DISC group and 19 to CONT group, respectively. Among the TAP/DISC group, 6(20.7%) and 8/14(57.1%) experienced disease flare after bDMARD tapering only and tapering/discontinuation respectively, whereas 2 (10.5%) of RA of the CONT group experienced disease flare during the follow-up (p=0.31 for RA tapering only and p=0.001 for RA discontinuing b-DMARD). In particular, RA of the TAP/DISC group who experienced disease flare after bDMARD modifications showed, at study entry, higher IHC scores for ST sublining CD68⁺cells (p=0.02), higher CD31⁺vessels count (p=0.01) and lower collagen deposition (p=0.04 and p=0.01 in lining and sublining, respectively) compared to RA not experiencing flare. Logistic regression analysis revealed that CD31⁺vessels count ≥ 12.8 at the time of sustained remission achievement [OR(95%ICs):5.7(1.0-32.1)] and TAP/DISC strategy [OR(95%ICs):5.4(1.3-22.7)] are independent factors associated to disease flare in RA patients in remission. In addition, regardless of the treatment modifications, synovial tissue of RA who experienced disease flare during the follow-up contained higher number of CD206^neg pro-inflammatory macrophage subpopulation at the time of sustained remission achievement, as compared to RA who maintained disease remission that showed mostly CD206^pos subpopulation (p=0.03).

Conclusion: Disease relapse is a common event in RA patients in sustained remission after b-DMARD discontinuation. The analysis of composition and phenotypes of synovial tissue cells identifies, at the time of remission achievement, RA patients at higher risk of disease flare after treatment discontinuation.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/histological-features-and-tissue-macrophage-phenotype-of-synovial-biopsies-identify-ra-patients-in-sustained-remission-at-risk-of-disease-flare-after-treatment-tapering-or-discontinuation/