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ACR23 – Day 3 Report

These year’s annual ACR Convergence has been a success with the return of an insanely active Poster Hall! F2F learning amidst miles of research and many young talented aside wizened establish presenters is such a welcome return to ACR, the way it should be.

Highlights from today included the induction of our new ACR President Deborah Dyett Desir (from Yale Univ.) and a host of new officers.  This along with cutting edge research during the plenary session and the Late-Breaking Abstract posters was just the tip of the iceberg of rheumatology research presentations.

Below are a few of my favorite presentations from day 3 at ACR 2023

  • MANDARA Study - Benralizumab in EGPA (Abstract L14). This phase 3 study compared the efficacy and safety of IL-5 therapies – Benralizumab (a monoclonal antibody against the IL-5 receptor) and Mepolizumab (an anti-IL-5 mAb) in patients with active EGPA (Eosinophilic Granulomatosis with Polyangiitis) also taking Standard of Care Therapy (SOC). The primary endpoint was a BVAS remission at both weeks 36 and 48. They enrolled 140 patients and the remission rate at both Weeks 36 and 48 was 59.2% for the benralizumab group and 56.5% for the mepolizumab group (p=0.7278), confirming non-inferiority. Relapse rates were the same for benralizumab and mepolizumab (both 30.0%). At Weeks 48–52, patients on BEN were more likely than MEP to reduce their glucocorticoid use (86.1% vs 73.9%). Serious AEs were reported in 5.7% of benralizumab and 12.9% of mepolizumab recipients.  Overall, benralizumab was non-inferior to mepolizumab over 52 weeks in patients with relapsing/refractory EGPA receiving SoC.
  • PR3+ Myeloid Cells in Proliferative Lupus Nephritis (Abstract 2427)  This plenary session study from Celia et al, was funded by the Accelerating Medicines Partnership (AMP), described yet another predictive urinary biomarker, PR3, a neutrophil degranulation product, that correlated with Renal Biopsy histological activity (NIH Activity score, not chronicity score), suggesting PR3 may be involved with renal pathology in lupus (SLE). Histochemical staining of renal biopsies from 11 SLE patients (5 membranous; 6 proliferative GN) showed impressive PR3+ staining in those with proliferative GN, mostly within glomeruli and less in the interstitium.  PR3+ cells (mostly phagocytes and PMNs) were increased in proliferative LN and indicate a more aggressive phenotype. The histologic changes suggest that intrarenal PR3+ cells are actively degranulating and contributing to kidney damage. Moreover, these findings are reflected in urinary PR3 levels and could lead to new therapeutic targets.  
  • Post Hoc EXXELERATE Analysis - High Titer RF and Response (Abstract 2148)   The EXXELERATE Trial was a head-to-head study of adalimumab (ATDA) vs. certolizumab (CZP) in RA and failed to show superiority of one drug over the other, even with a crossover design. This post hoc analysis was undertaken to study the concept that monoclonal antibody TNF targeted therapies may be affected by rheumatoid factor (RF) binding to the FC portion of these mAb based therapies. And the ideal comparison would be between ADA and CZP, with the latter not being an Fc construct. This study found those RA patients with the highest RF levels (upper tertile; ~>200 IU RF) had roughly 23% lower ADA plasma concentrations but no change in CZP plasma levels.  Moreover, patients with RF in the lower tertiles, there were no differences in DAS28-CRP scores between CZP- and ADA-treated patients. By contrast, those with high titer RF levels (RF >Q3), better drug responses were seen in CZP treated patients (mean DAS28-CRP scores were nominally lower) compared to ADA-treated patients. As these are post hoc analyses, future prospective studies are needed to confirm these findings and show that high titer RF patients may respond better to CZP.  Also, this finding was not observed in those with low vs. high titer ACPA RA.  To hear more about this study, visit this video interview with the author Dr. Josef Smolen from ACR 2023.


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