POS0259 ULTRASOUND AS AN IMAGING BIOMARKER OF EARLY RESPONSE TO TOCILIZUMAB AND METHOTREXATE IN VERY EARLY RHEUMATOID ARTHRITIS, TOVERA – A LONGITUDINAL STUDY
Authors: M. Stoenoiu, M. Maruseac, M. Messaoudi, A. Nzeusseu Toukap, E. Naredo
Journal: Annals of the Rheumatic Diseases (2021)

Background: The combination of methotrexate (MTX) and tocilizumab (TCZ) has been proven to be superior to MTX alone in early rheumatoid arthritis (RA) 1 and was able to prevent radiographic progression. Ultrasound (US) has become a valid imaging modality in managing RA. Together with clinical examination, US may allow a comprehensive monitoring of response to therapy. So far, few data are available concerning the early response to TCZ plus MTX in very early RA (VERA). Objectives: In this study we aimed to assess the early US response to TCZ plus MTX in VERA, DMARD-naïve patients. Methods: In this open-label, single-arm study, VERA patients received TCZ (162 mg/week, subcutaneously) and MTX (15-20 mg/week, per os ) for 24 weeks as induction therapy, followed by MTX as maintenance therapy. RA was diagnosed according to the 2010 ACR/European league against rheumatism (EULAR) criteria. All patients who fulfilled the inclusion criteria (ClinicalTrials.gov: NCT02837146 ) underwent blood tests, clinical and ultrasound examinations at the predefined time-points: 0,2,4,8,12,24,32,48,54 weeks (w). Ultrasound examination of 34 joints (elbows, wrists, MCP [1-5, bilateral], PIP ([2-5, bilateral], knees, ankles and MTP [2-5, bilateral]) was performed blindly to clinical data. Gray-scale (GS), power-Doppler (PD) scores, and the global OMERACT -EULAR synovitis score ( GLOESS ) were assessed in each joint. The sum of individual scores was calculated for 17-joint score (JS) (whole joint set), 10-JS (wrists, MCP, ankles and MTP joints), 12-JS 2 , and 7-JS 3 . Results: Forty-four patients (77% women), aged 46.7 ± 12.4 years, completed the 24-week period. Two-thirds (72.7%) were positive for anti-citrullinated protein antibody (ACPA) and 18.2% had bone erosions. At baseline, the mean 28 swollen joints count (28-SJC) was 7.55± 4.5, mean disease activity score (DAS28)-CRP score was 5.2 ± 0.15, mean simplified clinical activity score (SDAI) was 31.4 ± 1.9, mean clinical activity score (CDAI) was 29.1 ± 1.8 and mean health assessments questionnaire (HAQ) score was 1.3 ± 0.1. The C-reactive protein (CRP) decreased significantly at 2w (p&lt;0.05) and, accordingly DAS28-CRP score decreased significantly at 4w (p&lt;0.05). The 28-SJC and CDAI scores decreased significantly at 8w (p&lt;0.05). The HAQ and visual analogue scale (VAS) disease activity reported by patients decreased significantly at 8w (p&lt;0.05) and VAS fatigue at 12w (p&lt;0.05). The GLOESS and GS scores allowed us detecting the earliest significant treatment response at 2w and PD scores at 4w (p&lt;0.05). Among US joint subsets, 17-JS (p&lt;0.01), 12-JS (p&lt;0.05) and 10-JS (p&lt;0.05) were able to detect the earliest treatment response at 2w. The 7-joint score detected the earliest response at 4w, both in GS and PD (p&lt;0.05). Conclusion: US scores were able to detect therapeutic response to TCZ plus MTX earlier than clinical scores and may therefore be a promising imaging biomarker. References: [1]Burmester GR et al. Ann Rheum Dis 2017; 76; 1279-1284. [2]Naredo E et al. Arthritis Rheum 2008; 59(4): 515-522. [3]Backhaus M et al. Arthritis Rheum 2009; 61: 1194-1 201 . Disclosure of Interests: Maria Stoenoiu Grant/research support from: UCB, Roche, Abbvie, MSD, Sanofi, Celgene, Mihaela Maruseac: None declared, Mouna Messaoudi: None declared, Adrien Nzeusseu Toukap Grant/research support from: AbbVie, Eli Lilly, Janssen, UCB, Novartis, Celgene Corporation, Pfizer, Esperanza Naredo Grant/research support from: AbbVie, Roche, BMS, Pfizer, UCB, Eli Lilly, Novartis, Janssen, Celgene