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ACR 2024: What Exactly do JAKs and TYKs Do?

d 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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Addressing CV Risk in RA: Are we doing enough?

d Mrinalini Dey, MD

ORAL surveillance was a post-authorisation safety study of tofacitinib 5mg and 10mg versus TNF inhibitors, focusing on rates of adverse events, including MACE. A higher incidence of MACE was observed with the use of tofacitinib. Statins are recommended in patients with a history of atherosclerotic disease or 10 year predicted risk of MACE. But, how many patients with rheumatoid arthritis, at risk of MACE, are actually taking a statin?

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Phase 2 DAHLIA study in Sjogrens Anti-neonatal Fc receptor an “nipocalimab” w/remarkably encouraging results clinESSDAI significantly better at wk24, notably met QOL domains as well Finally getting good news in SjS! #ACR24 @RheumNow #ACRbest Abst#2527 https://t.co/e3uQmqJZ1o

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Mike Putman EBRheum ( View Tweet)
📢 Late breaking #2002 ➡️In ICI-induced arthritis, patients (n=100) report worsened pain, fatigue, & physical function vs population norms. ➡️High disease activity worsens symptoms #acr24 @RheumNow @jhrheumatology

Caoilfhionn Connolly CaoilfhionnMD ( View Tweet)

If a mother has had TNFi during pregnancy, can a baby have a live oral rotavirus vaccine (usually at 2mo)? This claims data suggests no increase in diarrhoea Adds to similarly reassuring 🇨🇦prospective cohort data https://t.co/2Tz9zRhPjz Vaccinate away! #ACR24 ABST0806 @RheumNow https://t.co/66OIAR8W6l

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David Liew drdavidliew ( View Tweet)
We use steroids carefully during pregnancy, and with good reason. SLR from @eular_org Task Force shows a dose-dependent effect of glucocorticoids on preterm birth. (of course, stable autoimmune disease hopefully means avoiding steroids altogether) #ACR24 ABST0810 @RheumNow https://t.co/elWsx5IXtB

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David Liew drdavidliew ( View Tweet)

📢Late-breaking #2003 🔑 Cappelli et al @jhrheumatology finds hip OA is NOT a significant risk factor for #ICI-IA 🔴#ICI-IA linked to lower mortality #ACR24 #ACRBest @RheumNow

Caoilfhionn Connolly CaoilfhionnMD ( View Tweet)

Fertility in RA. Improved outcomes in the T2T group. Abstr#1647 @RheumNow #ACR24 https://t.co/gLpY8enaEb

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Antoni Chan MD (Prof) synovialjoints ( View Tweet)
Shifting Trends in Initial RA Treatment Approaches A recent study by Sparks et al (Abstract #0509) reveals evolving trends in disease-modifying antirheumatic drug (DMARD) usage for rheumatoid arthritis (RA) over two decades in the U.S. https://t.co/6FN0WayZZR #ACR24 https://t.co/dc3CiNpKmx

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Dr. John Cush RheumNow ( View Tweet)
Abst#2413 SLE Cohort of > 2900 pts over 50 yrs - Prevalence of proteinuria at the time of SLE dx has not changed over the decades. Prevalence of proteinuria also did not change at 5 and 10 yrs after dx. Earlier use of HCQ has not led to a ⬇️in lupus nephritis. @RheumNow #ACRbest

TheDaoIndex KDAO2011 ( View Tweet)

Nice data from the OTIS Autoimmune Disease in Pregnancy Project re: certolizumab-exposed pregnancies: - spontaneous loss rate comparable to non-disease controls - no stillbirths - preterm similar to disease controls Plenty positive for CZP in pregnancy! #ACR24 ABST0805 @RheumNow https://t.co/XCRYsioxC0

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David Liew drdavidliew ( View Tweet)
A study exploring the benefits of treating RA patients to remission after achieving low disease activity (LDA). Key findings: - Among patients initially at LDA, achieving remission (CDAI ≤2.8) led to significantly better functional outcomes and reduced durable medical equipment… https://t.co/SNPKlRieur https://t.co/YIQNMf3Oap

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Antoni Chan MD (Prof) synovialjoints ( View Tweet)
We know most preexisting autoimmune disease is very mangaeable when checkpoint inhibitors are needed. So great to see that, in the VA, autoimmune disease pts largely haven't missed out on potentially lifesaving cancer immunotherapy. Keep on reassuring! #ACR24 ABST1985 @RheumNow https://t.co/ApOACBLi4K

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David Liew drdavidliew ( View Tweet)

Abst#1493 complete renal response (< 0.5 g/g w/< 10 mg/day pred); renal remission (UPCR < 0.3 g/g w/< 5 mg/day pred). 60 LN pts followed 3 yrs: 40% CRR & 19% RR. Pts not in CRR/RR had⬇️eGFR w/more decline in eGFR over time. No difference b/t CRR/ RR @rheumnow #ACRbest #ACR24

TheDaoIndex KDAO2011 ( View Tweet)

I have no doubt many of our RA patients will take GLP-1 agonists in the future. Here's some data @UCLA showing significant differences in not just body weight and HbA1c, but pain. Will be fascinating to see what it does for grumbling disease activity! #ACR24 ABST2259 @RheumNow https://t.co/HdOPACEo3A

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David Liew drdavidliew ( View Tweet)
Renal biopsies, while painful, remain the gold standard for diagnosing and classifying lupus nephritis. But what if there are less-invasive methods? In this article, I highlight key abstracts exploring innovative approaches. https://t.co/ZInKmVS2Gn @RheumNow #ACR24

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Akhil Sood MD AkhilSoodMD ( View Tweet)

What is #healthliteracy? Why is it important for our patients with #RMDs? Come to poster 1913 today at #ACR24 to find out about health literacy & outcomes in #InflammatoryArthritis For more information on this important topic, read my article @RheumNow https://t.co/llWs5aYtpK

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Mrinalini Dey DrMiniDey ( View Tweet)

RheumNow’s expanded coverage of the #ACR24 meeting is sponsored in part by Novartis. All content is chosen by RheumNow & its faculty.

Dr. John Cush RheumNow ( View Tweet)

Instead of just JAKi, why don't we look at all our RA meds and MACE risk FAERS data & reporting odds ratios here: all the caveats of voluntary reporting, so don't put too much weight, but... prednisone. Don't forget pred is really not great for MACE! #ACR24 ABST1981 @RheumNow https://t.co/L9SlPZF2Jd

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David Liew drdavidliew ( View Tweet)
Lung ultrasound for ILD in SSc/IIM would be great, no radiation and by the bedside - but a lot of skill required to interpret in reality. Maybe AI/computer vision can come to the rescue? Some nice models @StanfordRheum - will be watching this space! #ACR24 ABST1965 @RheumNow https://t.co/0uXBSVSE4c

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David Liew drdavidliew ( View Tweet)
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