Histologic and Clinical Correlates of Ultrasound Measures of Joint Inflammation: Analysis of RA Tissue Obtained by Ultrasound Guided Biopsy in Phase 2 of the Accelerating Medicines Partnership RA Network

Diane Horowitz¹, Andrew Filer ², Jennifer Albrecht ³, Arthur Mandelin ⁴, Darren Tabechian ⁵, Edward DiCarlo ⁶, Brendan Boyce ³, Ellen Gravallese ⁷, Peter Gregersen ⁸, Dagmar Scheel-Toellner ⁹, Kevin Wei ¹⁰, Katherine Liao ¹¹, Larry Moreland ¹², V. Michael Holers ¹³, Michael Brenner ¹⁴, Jennifer Anolik ³ and Vivian Bykerk ¹⁵, ¹Northwell Health, Great Neck, NY, ²Institute of Inflammation and Ageing College of Medical and Dental Sciences University of Birmingham, Birmingham, United Kingdom, ³University of Rochester Medical Center, Rochester, NY, ⁴Northwestern University Feinberg School of Medicine, Division of Rheumatology, Chicago, IL, ⁵University of Rochester, Rochester, NY, ⁶Hospital for Special Surgery, New York, ⁷University of Massachusetts Medical School, Worcester, MA, ⁸Feinstein Institutes for Medical Research, Manhasset, NY, ⁹University of Birmingham, Birmingham, United Kingdom, ¹⁰Brigham and Women's Hospital and Harvard Medical School, Boston, MA, ¹¹Brigham and Women's Hospital, Boston, ¹²University of Pittsburgh, PITTSBURGH, PA, ¹³University of Colorado Denver, Division of Rheumatology, Aurora, CO, USA, Denver, ¹⁴Brigham and Women’s Hospital:, Boston, ¹⁵Hospital for Special Surgery, New York City, NY

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Early Rheumatoid Arthritis, Synovial Immune Biology and ultrasound

Session Information

Date: Tuesday, November 12, 2019

Title: RA – Etiology & Pathogenesis Poster II

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: The AMP-RA network applies cutting edge molecular single cell technologies to study synovial tissue obtained from rheumatoid arthritis (RA) patients using US guided synovial biopsy (USGSB). Ultrasound can provide objective joint level measures of synovial inflammation, including hypertrophy (greyscale ultrasound, GSUS) and hyperemia (Power Doppler ultrasound, PDUS). Phase 1 AMP-RA demonstrated that USGSB was effective and safe for obtaining synovial tissue in the United States in patients with RA. In Phase 2 RA patients with active disease were recruited based on treatment exposure. We examined the relationship between joint level US variables, clinical characteristics, and synovial histology in Phase 2 patients.

Methods: In this multi-center study, eligible AMP-RA Phase 2 subjects had classifiable RA, ≥2 actively inflamed joints including the biopsied “sentinel” joint, a CDAI >10, and a GSUS of ≥2 of the biopsied joint. Biopsies were done using either QuickCore™ needle or Portal and Forceps. Subject Groups defined by treatment exposure were: (1) DMARD naïve/ minimally exposed ( ≤ 4 weeks of MTX)( (n=40), (2) MTX-IR despite ≥3 months of MTX (n=29), (3) TNF-IR despite ≥3 months of anti-TNF therapy. US scanned sentinel joints were scored using a 4-point semi-quantitative scale of GSUS and PDUS alongside composite RA disease activity measures. Retrieved tissue was fixed, stained and paraffin embedded, then sectioned and stained by H&E. Tissues were assessed for quality based on presence of and quantity of lining layer and synovium. Tissues were scored using 2 of 3 Krenn domains: lining layer (Krenn L)(0-3) and inflammatory infiltrate (Krenn I)(0-3) by three pathologists (BB, ED, EG).

Results: Of 119 synovial biopsies obtained from 13 sites across the USA and UK, 93 (83%) were of good quality. Clinical Groups 1, 2, and 3 had similar disease activity and US scores but the expected differences in disease duration (Table 1). GSUS, PDUS, CDAI, and Disease Duration were similar between the samples regardless of histology quality. Krenn scores differed between the Groups: Group 1 biopsies had higher mean Krenn(I) and Krenn(L) scores and a greater proportion with Krenn(L) and Krenn(I) scores of >1 (Table 2). PDUS grade correlated with the Krenn(L) and the Krenn(I) scores (p=0.003, r=0.32). GSUS grade failed to correlate with either histological measure (p=0.55, p=0.43 respectively).

Conclusion: In this cohort, the clinical and ultrasound characteristics did not correlate with tissue quality. Ultrasound measures of synovial hyperemia correlate with histologic joint infiltrates. Group 1 subjects had the shortest disease duration and least medication exposure. Despite such, Group 1 had higher mean Krenn(I) scores when compared to the MTX-IR (Group 2) and TNF-IR (Group 3) subjects.

Table1-DH

Table 1: Clinical, Ultrasound and Histology correlates for 3 clinical groups.

Table2

Table 2: Krenn scores for 3 Clinical Groups

Disclosure: D. Horowitz, None; A. Filer, None; J. Albrecht, None; A. Mandelin, None; D. Tabechian, None; E. DiCarlo, None; B. Boyce, None; E. Gravallese, None; P. Gregersen, None; D. Scheel-Toellner, None; K. Wei, None; K. Liao, None; L. Moreland, None; V. Holers, AdMIRx, 1, 2, 4, 5, 6, Alexion, 7, BMS, 5, Bristol-Myers Squibb, 5, Celgene, 5, Janssen R&D, 2, 5, Pfizer, 2; M. Brenner, None; J. Anolik, None; V. Bykerk, AbbVie, 5, Amgen, 1, 2, 3, 5, 8, Brainstorm Therapeutics, 1, 2, 3, 5, 8, Bristol-Myers Squibb, 5, Genentech, 5, Gilead, 5, NIH, 2, Pfizer, 1, 2, 3, 5, 8, Regeneron, 5, Regeneron Pharmaceuticals, Inc, 5, Sanofi, 5, Sanofi/Genzyme-Regeneron, 5, Sanofi-Genzyme/Regeneron, 1, 2, 3, 5, 8, Scipher, 1, 2, 3, 5, 8, The Cedar Hill Foundation, 9, UCB, 1, 2, 3, 5, 8, UCB Pharma, 5.

To cite this abstract in AMA style:

Horowitz D, Filer A, Albrecht J, Mandelin A, Tabechian D, DiCarlo E, Boyce B, Gravallese E, Gregersen P, Scheel-Toellner D, Wei K, Liao K, Moreland L, Holers V, Brenner M, Anolik J, Bykerk V. Histologic and Clinical Correlates of Ultrasound Measures of Joint Inflammation: Analysis of RA Tissue Obtained by Ultrasound Guided Biopsy in Phase 2 of the Accelerating Medicines Partnership RA Network [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/histologic-and-clinical-correlates-of-ultrasound-measures-of-joint-inflammation-analysis-of-ra-tissue-obtained-by-ultrasound-guided-biopsy-in-phase-2-of-the-accelerating-medicines-partnership-ra-netw/. Accessed .

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