POS0443 EXPLORING NOVEL TENOSYNOVITIS AND COMBINED INFLAMMATION IMAGING OUTCOMES: RESULTS FROM A RANDOMISED CONTROLLED TRIAL IN EARLY RHEUMATOID ARTHRITIS

Abstract

Background: Magnetic resonance imaging (MRI) trial outcomes have largely focused on synovitis, bone marrow oedema (BME) and erosions. Tenosynovitis is a common manifestation of rheumatoid arthritis (RA), but is relatively understudied; a combined inflammation score (CIS) summing synovitis, BME and tenosynovitis may be a highly responsive measure. We previously showed the responsiveness of the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and a machine-learning derived automated tool (RAMRIQ) in a randomised controlled trial (RCT) of tofacitinib and methotrexate (MTX) in MTX-naive patients (pts) with early RA.1 Objectives: This post hoc analysis assessed the impact of tofacitinib ± MTX on MRI tenosynovitis and CIS in pts with early RA using semiquantitative and quantitative MRI outcomes. Methods: Study A3921068 (NCT01164579), a 1-year, exploratory, Phase 2, RCT, compared tofacitinib 10 mg twice daily (BID) ± MTX, and MTX monotherapy, in MTX-naive pts with early RA.1 MRI of unilateral wrist and metacarpophalangeal joints was performed at screening/baseline (BL) and Months (M)1/3/6/12. MRI tenosynovitis and CIS were assessed using RAMRIS and RAMRIQ. Changes from BL (Δ) in RAMRIS and RAMRIQ tenosynovitis and CIS were evaluated at M1/3/6/12. Data were assessed using a mixed-effect model for repeated measures, with treatment arms as factors and BL values as covariates. Using data pooled across treatment arms, Spearman's rank correlation coefficients were calculated for associations between BL RAMRIS and BL RAMRIQ tenosynovitis and CIS vs BL Disease Activity Score in 28 joints, C-reactive protein (DAS28-4[CRP]), and ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS at M12 vs ΔDAS28-4(CRP) at M12. Results: In total, 109 pts were randomised and treated. ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS were generally significantly greater at M3/6/12 in pts receiving tofacitinib ± MTX vs MTX, while ΔRAMRIQ CIS was also significantly greater at M1 (Figure 1). Compared with RAMRIS, RAMRIQ outcomes were generally more responsive to treatment with tofacitinib ± MTX. Significant correlations were seen between BL RAMRIS and BL RAMRIQ tenosynovitis and BL RAMRIS CIS vs BL DAS28-4(CRP), and between ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS at M12 vs ΔDAS28-4(CRP) at M12 (Table 1). In general, stronger correlations were seen between BL DAS28-4(CRP) and BL RAMRIS vs BL RAMRIQ parameters, while correlations were similar between ΔDAS28-4(CRP) at M12 and ΔRAMRIS and ΔRAMRIQ parameters at M12. Conclusion: Responsiveness of RAMRIS and RAMRIQ tenosynovitis and CIS was demonstrated with significant improvements through M12 in pts receiving tofacitinib 10 mg BID ± MTX vs MTX. Construct validity for RAMRIS and RAMRIQ tenosynovitis and CIS was evident from correlations with DAS28-4(CRP). Further work is needed to validate these novel imaging biomarkers in terms of relative responsiveness and prediction of later structural progression.