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After failing a JAK inhibitor, can you still hit a JAK-pot?
Januse kinase (JAK) inhibitors are targeted synthetic disease modifying anti-rheumatic drugs (tsDMARDs) that have risen in popularity as earlier treatment options for rheumatoid arthritis.
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JAK Inhibitors in Refractory Adult and Childhood-Onset Still’s Disease
Still's disease is an autoinflammatory disease characterized by spiking fever, rash, polyarthralgia, sore throat and even life-threatening complications, such as macrophage activation syndrome. It was first described by George Still in the late 1800s.
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Baricitinib for *relapsing* GCA (Th1+Th17)
w abbreviated steroid wean (15-22w)
Despite being tougher to treat:
100% off steroids at 24w
93% off steroids at 52w
no ischemic Sx
promising as another GCA Rx option!
(post-cessation 4pts flared)
@MayoClinic #ACR21 ABST1396 @RheumNow https://t.co/dqFnHQYogk
David Liew drdavidliew ( View Tweet)
This feels like an excellent starting point for Tuesday's ORAL Surveillance malignancy discussion.
RWE Cohort: HR 1.01 (0.83-1.22)
RCT-dup Cohort: HR 1.19 (0.86-1.64)
ORAL Surveillance: HR 1.48 (1.04-2.09)
Interesting day 4 ahead!
great talk @SeoyoungCKim #ACR21 7S413 @RheumNow https://t.co/YSau21goMr
David Liew drdavidliew ( View Tweet)
Abstr 0983 mRNA SARS-CoV-2 Vaccine in RA Patients
Rubbert-Roth and colleagues found:
- RA patients developed anti-S1 antibodies slower and lower compared to controls
- Reduced titers among Abatacept & JAKi users
#ACR21 @RheumNow https://t.co/sXW8d53O8m
Akhil Sood MD AkhilSoodMD ( View Tweet)
TOFA Post hoc analysis on 2000pts:
⬆️ Paraoxonase PON1 activity associated w/
⬇ risk of malignancies (not NMSC) in RA pts treated w/ TOFA, Adj on RA duration, age, and smoking.
A promising biomarker! #Abst980 @RheumNow #ACR21 https://t.co/fOILnAyDN9
Aurelie Najm AurelieRheumo ( View Tweet)
#ACR21 Abst#0588. TNF vs non-TNFi in obese RA pts
⭐️TNFi use ⬆️ disease activity vs ABA in obese pts
⭐️TNFi use ⬆️ activity vs TCZ in non-obese pts
⭐️No diff w RTX, Tofa
▶️Further research needed: Wt-based dosing? SC vs IV?
https://t.co/K8WycPTgxW @Rheumnow #ACRBest
Links:
Eric Dein ericdeinmd ( View Tweet)
ORAL Surveillance MACE conclusions:
So this is fair: tofacitinib acts as a CV risk factor, there are many others, we need to address CV risk in RA pts.
Nevertheless, in terms of MI risk, tofa vs TNFi, if I had one CV risk factor, I know what I'd do.
#ACR21 ABST0958 @RheumNow https://t.co/4Z79XtTzl9
David Liew drdavidliew ( View Tweet)
SELECT-AXIS 1: UPA 15 mg QD consistently efficacious over 2 years for ASAS40. Low radiographic progression rates in AS pts. No new safety findings were observed. Abs 0924 #ACR21 #RheumNow @RheumNow https://t.co/CWvH1OPGyR https://t.co/uC67fJZDCE
Dr. Rachel Tate uptoTate ( View Tweet)
Abst0509 #ACR21 @RheumNow study of plasma concentrations of Deucravacitinib show high functional selectivity for TYK2 while Tofa, Upa & Bari inhibit JAK1/2/3 to varying degrees show no meaningful inhibition of TYK2. Distinct class of kinase inhibitor as compared to JAKs
Olga Petryna DrPetryna ( View Tweet)
With Deucravacitinib, a TYK2 inhibitor vs placebo, PsAID-12 and PsAID-9 scores were significantly improved
versus baseline at Week 16
and other PROs showing a clear improvement in PsA-related impact @RheumNow #ACR21 Abst#0750 https://t.co/JbeSE2dO94 https://t.co/pH79dXCYSs
Dr. Antoni Chan synovialjoints ( View Tweet)
Let's look at MI first.
Well, the numbers don't look great for tofa here.
fatal MI very small numbers
non-fatal MI - well that doesn't look good
(do we have combined both tofa doses vs TNFi?)
HR > 2 seems less than ideal - this would represent a substantial RF
#ACR21 @RheumNow https://t.co/5HSXFrMJCu
David Liew drdavidliew ( View Tweet)
ORAL Surveillance: MACE events higher in TOFA vs TNFi. Independent risk factors: smoking, aspirin use, age ≥ 65 yrs, and male sex; TOFA vs TNFi tx in these pts assoc'd w/ numerically higher MACE incidence. Plenary Abs 0958 #ACR21 #ACRbest @RheumNow https://t.co/44af1KujqP
Dr. Rachel Tate uptoTate ( View Tweet)
Tofacitinib vs TNF inhibitors in #RA patients +50yrs with >1 CV risk factor; the data from ORAL Surveillance that we have all been waiting for! #ACR21
Risk of MACE related largely to baseline CV risk https://t.co/SpuKTtP8ql
The Lancet Rheumatology TheLancetRheum ( View Tweet)
ORAL-Surveillance, an open label Phase 3b/4 RCT of tofacitinib (JAKi) vs TNFi in RA
Numerical elevations in MACE and MI, highest among pts w/hx of CAD or high 10-year risk for MACE
I have been considering baseline CVD / VTE / CA risk when prescribing these since this broke https://t.co/8DAx8IgnZM
Mike Putman EBRheum ( View Tweet)
ORAL surveillance TOFA vs. TNFi:
in patients with > 50yo > 1 CV risk MTX IR
-# ⬆️ in MACE and MI (not stroke)
-MACE risk factors on TOFA smoking, >65 male gender
-# ⬆️ MACE in its w/ any of these RF
What are you going to tell your patients? #Abtr0958 #ACR21 #ACRBest @RheumNow https://t.co/81kVTH63bb
Aurelie Najm AurelieRheumo ( View Tweet)
MACE risk Tofa vs TNFi ORAL surveillance: age 50+ w/1 additional CV risk, MTX-IR
👉higher # MACE, MI in Tofa 5 or 10 mg bid (no increase in stroke)
👉risks for MACE w/tofa: tobacco, ASA, age 65+, male sex
👉counsel high risk pts (?avoid use)
Abst#0958 #Plenary #ACR21 @rheumnow https://t.co/tg35cts9tw
TheDaoIndex KDAO2011 ( View Tweet)
Oral Surveillance outcomes in a nutshell Tofacitinib two doses vs TNFi event driven trial more AEs of interest in Tofa groups MACE Malignancy SIE in older groups VTE esp #tofacitinib 10 mg BID @RheumNow #ACR21 #ACRBest abst#0958 https://t.co/j39g7yVVFB
Janet Pope Janetbirdope ( View Tweet)
1133 MACE events in Oral Surveillance study - Tofa use in high risk pts had more MACE events than TNFi use. Abstr# 0958 #ACR21 Problems with the gimmish are:
- Older patients, w/ Hi CV Risk
- 50% prednisone use
- Use of TNFi as comparator (effective at lowering CV risk) https://t.co/lzIyhgzvRe
Dr. John Cush RheumNow ( View Tweet)
⭐️IR for MACE, MI, non-fatal MI numerically ⬆️ in Tofa vs. TNFi
⭐️HR for MACE/MI/stroke >1 for Tofa vs. TNFi
⭐️Risk factors: Smoking, ASA use, Age>65, men
⭐️Pts without risk factors, IR for MACE were similar
Abs#958
#ACR21 @RheumNow #ACRBest
https://t.co/xA3aGu5Sqi https://t.co/VnPHBhrmdx
Robert B Chao, MD doctorRBC ( View Tweet)
