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ORAL Surveillance - Is Statin Use the Problem/Solution?

Eric Dein, MD

The findings from ORAL Surveillance Study have been a dominant conversation at recent ACR Convergence, with the seminal findings and subsequent analyses a target of debate. Subsequent post-hoc analyses, follow-up studies, and claims data analyses have been used to further interpret the data, though a clear answer on safety is not certain. A study presented on Sunday reported on a new post-hoc analysis that provides new insights.

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ACR 2024: What Exactly do JAKs and TYKs Do?

Michael Putman, MD, MSCI

Let me start by confessing something embarrassing: the immune system is just too complex for me to understand. I suspect the onslaught of new drugs with new mechanisms at ACR 2024 may have left many of you feeling similarly. This may be particularly true for the TYK/JAK/STAT signaling pathway, where each agent has a slightly-different combination of binding affinity to various JAK and TYK signaling dimers. In this article I want to share some diagrams from ACR 2024 that may help.

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ACR 2024 - Day 2 Report

Jack Cush, MD

Plenary sessions began the day, followed by thousands on the abstract floor. Here are a few of my favorite presentations from day 2 at ACR 2024.

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JAKi in inflammatory myositis?

Janet Pope, MD, MPH, FRCPC

Abstract 1731 is a small RCT of baricitinib in inflammatory myositis comparing early start baricitinib to later start.

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I've shared some thoughts on @RheumNow on methotrexate, tocilizumab, and baricitinib in PMR based on #ACR24 https://t.co/WXiW1nLN4k

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Richard Conway RichardPAConway ( View Tweet)

A#2583 Apremilast for axial inflamm in PsA, assess by CANDEN MRI scoring MOSAIC P4 open label trial Reduction in inflammation seen in vertebral bodies & posteriolateral, not in facet joints No changes in SPARCC SIJ, spine - though low baseline SIJ inflammation @RheumNow #ACR24 https://t.co/3GKEGJbtdc

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Eric Dein ericdeinmd ( View Tweet)
A#2584 Mease Zasocitinib TAK-279 - potent, selective TYK2i P2b, 12w PsA RCT 15/30 mg - similar response, better than PBO for ACR20/50/70, MDA, DAPSA, PASDAS 29% MDA v 13% PBO Safety no signal for MACE, cancer, serious ifn, death. Mild acne signal noted @RheumNow #ACR24 https://t.co/1eqD9R5fLe

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Eric Dein ericdeinmd ( View Tweet)

Selective TYK2i zasocitinib, results of Phase 2 DBRCT Dose dependent improvements in various PsA outcomes; NNT~5 for DAS28 remission, NNT~20 for PASDAS Hard to compare to current agents, somewhere between JAKs (woot!) & "apremlist zone" 🫣 #ACR24 @RheumNow Abstr#2584 #ACRbest https://t.co/t0y6C618ll

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Mike Putman EBRheum ( View Tweet)
A#2586 EBIO study - secukinumab on entheseal bx in PsA. Compare b/l to 3+ mo on SEC Biopsy: change of entheseal cell composition on IL-17A Rx - decr Il-17A producing cells in responding pts Spatial transcriptomics - colocalizarjon of ILC2, CD200+ fibroblasts @RheumNow #ACR24 https://t.co/kMiqpBRxuE

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Eric Dein ericdeinmd ( View Tweet)
Triboulet et al. JAKi in RA-ILD. 42 patients. Stability of PFTs over median 21 months. HRCT stable in 62%. Progressive ILD on HRCT in 19%. @RheumNow #ACR24 Abstr#2249 https://t.co/PY9BrCfNHc https://t.co/r8fIgrjyDu

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Richard Conway RichardPAConway ( View Tweet)
Early observational data suggesting JAK inhibitors can play a role in TAK tx We have seen this with UPA in GCA this conference… time for SELECT-TAK ! @RheumNow #ACR24 https://t.co/B2Wa8sOFTp

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Brian Jaros, MD Dr_Brian_MD ( View Tweet)
Lots of data on TYKs including much supporting efficacy in interferon inhibition Can we really call interferon signalling a "central" pathway in SLE? Inhibiting it has been modestly successful, at best, and mostly for skin dx #ACR24 @RheumNow Abstr#2434 https://t.co/Q94FQz3gzO

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Mike Putman EBRheum ( View Tweet)

Always looking for cancer/CV signals from JAKi in big observational datasets w extensive JAKi use nationwide 🇯🇵 claims data RA pts n=52k (JAKi n=4.3k) Cancer with JAKi vs TNFi: aHR 2.2 (esp lung, lymphoma) This is a problem. Watch these data. #ACR24 ABST1336 @RheumNow #ACRBest https://t.co/vsnT46De6T

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David Liew drdavidliew ( View Tweet)
Upadacitinib in Behcet's disease - would be very much welcomed, and this open label 8 patient pilot from China is encouraging. We saw similar data for tofacitinib before @ARD_BMJ: https://t.co/YlAQVXpnTY JAKi (?generic) could be a fantastic option! #ACR24 ABST2515 @RheumNow https://t.co/65friNLUOK

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David Liew drdavidliew ( View Tweet)
Here's a meta-analysis of MACE/malignancy in JAKi vs TNFi in observational cohort studies. All the epidemiological challenges here aside, it's a good reminder that with ORAL Surveillance it's *cardiovascular risk enriched pts* we're concerned about. #ACR24 ABST2264 @RheumNow https://t.co/vIXlrI3V2d

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David Liew drdavidliew ( View Tweet)
We saw evidence for JAK use in GCA this conference... what about IL-1 inhibition? Double-blind RCT: Anakinra vs. PBO w/ similar GC taper in GCA pt NO difference in relapse rate at 26, 52 wks despite addition of Anakinra @RheumNow #ACR24 Abst1699 https://t.co/gUb0gGJjTG

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Brian Jaros, MD Dr_Brian_MD ( View Tweet)

Super helpful results from COVER study, holding JAK or IL17 for COVID boosters Antibody titers went up regardless of holding Holding caused flares (14-25% increase!) Pretty clear message; continue JAK / IL17 #ACR24 @RheumNow Abstr#1718 #ACRbest https://t.co/Mf89dWrRWz

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Mike Putman EBRheum ( View Tweet)
Comparison of infection risk across b/tsDMARDs in IA in real-world study Treatment with ➡️Rituximab ➡️JAKi ➡️Anti-IL6 assoc with ⬆️⬆️ risk of severe infection compared to TNFi A reminder to consider comorbidities & infection risk in selecting b/tsDMARDs Ab1716 #ACR24 @RheumNow

Mrinalini Dey DrMiniDey ( View Tweet)

Interesting comparative effectivness study, TOFA vs calcineurin inhibitors in MDA5-dermato Expansion of prior publication @NEJM that used historical controls: https://t.co/AzA8ybCqYH Encouraging data for JAKs in this disease; need proper trials #ACR24 @RheumNow Abstr#1736 https://t.co/BHVMZLu6Ip

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Mike Putman EBRheum ( View Tweet)
Wu et al. MDA5-DM. Propensity-score cohort study. 672 patients. Tofacitinib vs CNI. Primary outcome 1 year death or lung transplant. HR 0.70 favouring tofacitinib. @RheumNow #ACR24 Abstr#1736 https://t.co/A0aHhp1q9c https://t.co/LbutJDBllr

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Richard Conway RichardPAConway ( View Tweet)
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