OP0084 DIGITAL SPATIAL PROFILING REVEALS DISTINCT SYNOVIAL TISSUE MACROPHAGE TRANSCRIPTOMIC SIGNATURE OF SUSTAINED REMISSION IN RHEUMATOID ARTHRITIS PATIENTS AT RISK OF DISEASE FLARE AFTER TREATMENT CESSATION

Background Sustained remission is the treatment goal for Rheumatoid Arthritis (RA) and once achieved patients are eligible to tapering or discontinuation. However, this exposes occurrence of unpredictable disease flare, date there no definitive predictive biomarkers flare RA in that could be used clinical practice. Objectives To assess impact classification on synovial tissue (ST) features sustained identify flare. Methods 200 (102 with DAS<1.6 98 fulfilling Boolean criteria at least 9 months, respectively) ultrasound (US) (PD negative) under Methotrexate without biological-Disease Modifying Anti-Rheumatic Drugs (bDMARDs) were enrolled underwent US guided ST biopsy. 373 naive included as comparison. For each patient, synovitis degree was determined using a H&E-based semiquantitative score 1 . Some samples macrophage (STMs)(CD206/MerTK) FACS phenotyping digital spatial profiling (GeoMx DSP, Nanostring) quantitate transcript abundance CD68 pos cells 138 spatially distinct regions interest (ROI). After study entry, randomly assigned tapering/discontinuation (TAP/DISC) (tapering c- b-DMARD 6 months discontinuing bDMARD afterwards) maintaining same therapeutic scheme (CONT). Each followed every 3 rate after modifications 24 months. Results Regardless either DAS- Boolean-defined, had significantly lower KSS than (p<0.0001 both). (p<0.0001) enriched CD206 MerTK STMs (p=0.0012) compared DAS-defined RA. 73(36.5%) experienced regardless change during follow-up. Stratifying based definition group, who within follow-up had, higher maintained remission, (CONT:p=0.0027 TAP/DISC:p=0.0011). Logistic regression analysis revealed baseline KSS?3 [AUC:0.748(95%CI:0.649-0.846)p<0.0001] an independent factor [OR:6.9(95%CI:2.82-16.81)] Conversely, did not differ entry both CONT (p>0.05) TAP/DISC group relation considering phenotype, low levels (<38.1%), more likely subgroup ?38.1% (p=0.0014). confirmed that, before change, phenotype (CD206 <38.1%) predictor [OR:6.25(95%CI:1.33-29.43)] Finally, DSP morphology marker, lining sublining layer transcriptomics distinguished, baseline, flared modification from those not. Conclusion Disease common event modification. identified by flow cytometry transcriptomic can risk Thus, defined panel markers histological biopsy tissues way forward predicting References [1]Alivernini S, et al. & Rheumatology 2021 Disclosure Interests Simone Perniola: None declared, Barbara Tolusso: Aziza Elmesmari: Marco Gessi: Clara Di Mario: Maria Rita Gigante: Luca Petricca: Dario Bruno: Domenico Somma: Annamaria Paglionico: Valentina Varriano: Laura Bui: Antonietta D’Agostino: Mariola Kurowska-Stolarska Grant/research support from: Pfizer, GSK, Novartis, Eli Lilly, Elisa Gremese Speakers bureau: Abbvie, BMS, Galapagos, Pfizer., BMS., Stefano Alivernini GSK.