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Who gives a ‘JAK’ why and how they work, as long as they do!
Several abstracts have studied the mechanism of action of JAK inhibitors (JAKi) in various diseases. JAKi alter many other mediators affected by the JAK STAT pathway. For instance, T cell signature in blood that is proliferative was associated with a response in RA.
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Glucocorticoids-free zone in SLE?
For over 70 years, glucocorticoids, (GC) have been a part of standard therapy in SLE. They are classically used to not only induce remission or treat an acute flare, but also as maintenance therapy. They are a valuable 'friend' if used wisely, and can become a 'foe' if used excessively.
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Phase 2 RCT of TLL-018 (JAK1/TYK2i) vs Tofa in RA. 101 patients. ACR50 72% vs 42%. 83% of tofa-IR achieved ACR50 on TLL-018. Can't wait for the phase 3 data! Abstr#0840 #ACR23 @RheumNow #ACRbest https://t.co/wjGx4Edxyb https://t.co/n6CL8G01Wo
Richard Conway ( View Tweet)
TLL-018, the dual JAK1/Tyk2 inhibitor which caused all the chatter at #EULAR2023, now with more full data showing it absolutely smash tofacitinib in RA, with similar safety.
“This is a spectacular compound - unbelievably spectacular” - Roy Fleischmann
#ACR23 ABST0840 @RheumNow https://t.co/nIKQb4yYrJ
David Liew drdavidliew ( View Tweet)
More on TLL-018
How?
A: Everyone surprised. But maybe dual mech benefits re: pain via IFN
Where’s the multinational RCT in RA?
A: Priority on rapid registration in China, quickly. But ph2 trials for psoriasis happening in US, results so far look consistent.
#ACR23 @RheumNow
David Liew drdavidliew ( View Tweet)
Fascinating how upadacitinib may well have an effect on pain in RA, beyond inflammation.
Now seen similar for bari in RA & guselkumab in PsA. And, if real, for some people could be a massive get. Love to see dedicated studies
SELECT-COMPARE post-hoc #ACR23 ABST0429 @RheumNow https://t.co/Tk278mGJYY
David Liew drdavidliew ( View Tweet)
Ab#0596 #ACR23 @RheumNow
R Furie on Decravacitinib in SLE
48wk double-blind trial. PBO v DEU 3mgBID, 6 mgBID,12 mg qd
Higher response, faster time to SRI(4), BICLA and dual response v PBO. More likely to sustain response from w32-48. https://t.co/M34d3nQmwv
Eric Dein ( View Tweet)
Abs#518 @RheumNow #ACR23
Deodhar: TOFA in AS, by b/l CRP levels
30% nml CRP (<5 mg/L) v 70% Elevated
At wk 12, TOFA >> PBO regardless of b/l CRP
Difference in response: greater in pts w elevated CRP
Safety rates: elev. CRP c/w PBO, but nml CRP had trend of high AEs for tofa v PBO https://t.co/b9NRNkU8ub
Eric Dein ( View Tweet)
Upadacitinib on wearable device-measure activity
SELECT-AXIS 2
Abs#0530 #ACR23 @RheumNow
UPA had numerically higher mean daily step counts than PBO
11% improvement v PBO at wk 14 (diff of 345 steps/day)
Sedentary pts: 22% improvement in daily step count from b/l on UPA (4% PBO) https://t.co/Gq91TmvfZC
Eric Dein ( View Tweet)
Good Treatment review of biologics (IL-1, IL-6) in systemic JIA (Stills) including complications of #MAS and lung disease; also info on horizon therapies like JAK inhibitors and IL-18 targeting and novel biomarkers (calgranulins, IL-18 and CXCL9) https://t.co/Cbd7bKdIbb https://t.co/d9tn9fmSAy
Dr. John Cush RheumNow ( View Tweet)
Tofacitinib efficacy and safety in axSpA pts by baseline CRP levels
Elevated CRP pts with higher response in ASAS20, ASAS40, BASDAI50, etc.
AE trended higher in normal CRP pts taking Tofa compared to placebo
@RheumNow #ACR23 Abs#0518 https://t.co/nbiD36x1Pa
Robert B Chao, MD ( View Tweet)
Deucravacitinib (TYK2) data has been surprisngly good in SLE
Strong rationale in PsA as well; I liked this poster & the focus on pain scores / patient QOL
Probably my #1 draft pick for "drugs I'm buying right now"
@RheumNow #ACR23 Abstr0508 https://t.co/FHNvgUrYxp
Mike Putman EBRheum ( View Tweet)
Year in Review: Dr. P Seo
Novel PsA therapy on the horizon:
⭐️Brepocitinib
➡️ Tyk-2 inhibitor: IL12/23 & type I IFN
➡️ Phase Ib, 218 pts, 8% TNFi failure
➡️ 71% on concurrent MTX
➡️ Wk 16: ACR 50/70 & PASI75/90 improved, maintained through week 52
#ACR23 @RheumNow
Meral K. El Ramahi, MD MeralElRamahiMD ( View Tweet)
I’m not TYK’ed! Another TYK2 #TAK-279 in #PsA RCT. Yup it works in ballpark of other PsA #Rx. #PASI75 45.7%. No obvious dose response w 15 and 30 mg daily but more #acne at higher dose. #ACR23 @ACRheum @RheumNow poster L12 Where to use vs #Deucravitinib? Too early to say as Ph2 https://t.co/nMkgOlUf6s
Janet Pope ( View Tweet)
Nice VA study evaluating risk of lung cancer w/respect to RA treatment strategies
Take home? No association. Aside from the (small risk) w/JAKi's, I think malignancy risks have been mostly overblown
@NamrataRheum @RheumNow ABST0453 #ACR23 https://t.co/lDz0nV1KHt
Mike Putman EBRheum ( View Tweet)
Patient reported outcomes between clinic visits: worth doing?
RA pts starting ADA/UPA, n=150
ArthritisPower/PatientSpot app for PROs between visits
52% of CDAI change explained by PROs
Maybe a helpful tool in prioritising RA clinic reviews?
@RADoctor #ACR23 ABST0380 @RheumNow https://t.co/oTttAlIxQR
David Liew drdavidliew ( View Tweet)
Who knew? VEXAS =cluster of findings from a somatic mutation N=110 studying retention of advanced Rx. #JAKi had far better retention than other #Rx. Although there could be channeling bias, I am impressed! Access for off label is a different issue #L03 #ACR23 @RheumNow @ACRheum https://t.co/RE4BVdZeWt
Janet Pope ( View Tweet)
In bDMARD-IR AS patients, UPA led to numerically greater improvements vs PBO in physical activity as measured by a wearable device over 14 wks, especially in sedentary patients. #ACR23 Abs #0530 https://t.co/6Me2XctK6D @rheumnow https://t.co/c6E2GfAGt4
Dr. Rachel Tate ( View Tweet)
Join us tonight at 6pm PT/ 9pm ET for our daily #ACR23 recap. https://t.co/0RDwTdzhwS
Dr. John Cush RheumNow ( View Tweet)
Good Treatment review of biologics (IL-1, IL-6) in systemic JIA (Stills) including complications of #MAS and lung disease; also info on horizon therapies like JAK inhibitors and IL-18 targeting and novel biomarkers (calgranulins, IL-18 and CXCL9) https://t.co/ACe7nDDwop https://t.co/lV66WerkAp
Dr. John Cush RheumNow ( View Tweet)
