POS0259 ULTRASOUND AS AN IMAGING BIOMARKER OF EARLY RESPONSE TO TOCILIZUMAB AND METHOTREXATE IN VERY EARLY RHEUMATOID ARTHRITIS, TOVERA – A LONGITUDINAL STUDY

Abstract

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-JS2, and 7-JS3.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<0.05) and, accordingly DAS28-CRP score decreased significantly at 4w (p<0.05). The 28-SJC and CDAI scores decreased significantly at 8w (p<0.05). The HAQ and visual analogue scale (VAS) disease activity reported by patients decreased significantly at 8w (p<0.05) and VAS fatigue at 12w (p<0.05).The GLOESS and GS scores allowed us detecting the earliest significant treatment response at 2w and PD scores at 4w (p<0.05). Among US joint subsets, 17-JS (p<0.01), 12-JS (p<0.05) and 10-JS (p<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<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.