POS0443 EXPLORING NOVEL TENOSYNOVITIS AND COMBINED INFLAMMATION IMAGING OUTCOMES: RESULTS FROM A RANDOMISED CONTROLLED TRIAL IN EARLY RHEUMATOID ARTHRITIS
Authors: P. G. Conaghan, M. Østergaard, O. Troum, Z. Xie, A. Brett, M. Snyder, A. Ebrahim, D. Chapman, G. Sawyerr, J. Andrews
Journal: Annals of the Rheumatic Diseases (2021)

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-naïve 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-naïve 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. Table 1. Correlations between a) BL RAMRIS and BL RAMRIQ tenosynovitis and CIS vs BL DAS28-4(CRP) (N=109) and b) ΔRAMRIS and ΔRAMRIQ tenosynovitis and CIS at M12 vs ΔDAS28-4(CRP) at M12 (N=73) across treatment arms a a ) BL DAS28-4(CRP ) b ) ΔDAS28-4(CRP ) BL imaging feature Correlation p value ΔImaging feature Correlation p value RAMRIS tenosynovitis 0.366 0.0001 RAMRIS tenosynovitis 0.531 &lt;0.0001 RAMRIS CIS 0.399 &lt;0.0001 RAMRIS CIS 0.554 &lt;0.0001 RAMRIQ tenosynovitis 0.205 0.037 RAMRIQ tenosynovitis 0.543 &lt;0.0001 RAMRIQ CIS 0.180 0.062 RAMRIQ CIS 0.564 &lt;0.0001 a Data were pooled across the tofacitinib 10 mg BID ± MTX and MTX monotherapy arms Spearman’s rank correlation coefficients and p values were calculated for associations between RAMRIS and RAMRIQ parameters and DAS28-4(CRP); tenosynovitis and CIS were assessed using combined data from metacarpophalangeal and wrist joints; CIS is the sum of synovitis, BME and tenosynovitis values Δ, change from BL; N, number of pts with values at BL/timepoint of interest 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. References: [1]Conaghan et al. Ann Rheum Dis 2016; 75: 1024-1033. Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by Jennifer Arnold, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests: Philip G Conaghan Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Flexion, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Regeneron, Mikkel Østergaard Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, Consultant of: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, Grant/research support from: AbbVie, Centocor, Merck, Orrin Troum Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Horizon, Novartis, Pfizer Inc, Sanofi-Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Horizon, Pfizer Inc, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Centocor, Corrona, Novartis, Pfizer Inc, Zhiyong Xie Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alan Brett Shareholder of: Stryker Corp, Employee of: Stryker Corp, Mark Snyder Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Abbas Ebrahim Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Douglass Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gosford Sawyerr Consultant of: Pfizer Inc, Employee of: Syneos Health, John Andrews Shareholder of: Pfizer Inc, Employee of: Pfizer Inc