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Polymyalgia rheumatica immunological puzzle further illustrated
Infiltrating macrophages expressing IL-6 and GM-CSF may drive the subacromial bursitis often seen in polymyalgia rheumatica, according to new research (abstract OP0015) prese
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SLE trials update
Translating targeted therapy from bench to bedside has been more problematic in SLE than other autoimmune diseases, with many theoretically well-founded agents appearing to have failed in clinical trials as a result of inefficacy, problem with trial design and/or safety issues.
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Are JAKi fulfilling their promises in RA? H Schulz-Koops said a survey showed rheumatologists wanted effective fast acting Rx that could be used as monotherapy. @eular_org #EULAR2022 @RheumNow https://t.co/Gdel9YnAzA
Janet Pope Janetbirdope ( View Tweet)
VIGIBASE registry RA
39000+ pts JAKi and 231000+ pts TNFi
*No increase in MACEs with JAKi 1.4% vs. 0.9%
*JAKi Increase in DVT RR 3.99
and PE RR 3.5
adjusted on age and sex
@RheumNow #OP0268 #EULAR2022 #Lupus https://t.co/hiAvKctgky
Aurelie Najm AurelieRheumo ( View Tweet)
Some / most of promises of #JAKi are fulfilled. Efficacy, adherence = on mono vs combination Rx with MTX. But some emerging safety issues. NK cells reduce inflammation of NK cells on fibroblasts re other MOA. @eular #EULAR2022 @RheumNow The promise of #JAKi I RA https://t.co/8Ry3vVMyzO
Janet Pope Janetbirdope ( View Tweet)
#ClinicalPearl. Why do doctors prescribe #JAKi in RA? Efficacy, fast onset, X-ray inhibition, can work as monotherapy, remission - in order of diminishing frequency BUT I will add access and oral (convenience). POS0680 @RheumNow @eular_org #EULAR2022 https://t.co/XHtNqguqvh
Janet Pope Janetbirdope ( View Tweet)
JAK will quiet Still’s disease? 7 w Still’s 4 refractory disease had benefit w #JAKi POS0014. Needs more data but looks promising most w partial response . 5 on #Tofacitinib and 2 w #Baricitinib. @eular_org #EULAR2022 POS0014 @RheumNow https://t.co/j9IRgT9XJf
Janet Pope Janetbirdope ( View Tweet)
Insightful session with H Schulze-Koops: JAKi-Are all promises fulfilled?
"JAKi have not shown us sufficient data to prove that they can induce remission or inhibit disease progression"
@RheumNow #EULAR2022 https://t.co/SKKAS1ViIU
Aurelie Najm AurelieRheumo ( View Tweet)
Meudec et al. Comparative effects of JAKi on NK cell function on cancer cells (lymphoma and lung cancer). Tofacitinib had most negative impact. Interesting given blanket black box based on tofa data! @RheumNow #EULAR2022 OP0265 https://t.co/XSE7hP60Ui https://t.co/MjtAJcvWAD
Links:
Richard Conway RichardPAConway ( View Tweet)
Nyam et al. JAK-pot study. >90000 treatment courses. No difference in aHR for treatment stop due to adverse events in JAKi vs TNFi or non-TNF bDMARD. @RheumNow #EULAR2022 OP0266 https://t.co/3tgADvH1Bq https://t.co/2qLRzfMB9c
Links:
Richard Conway RichardPAConway ( View Tweet)
Szekanecz et al. ORAL Surveillance. Geographic differences in MACE largely driven by history CVD and high baseline risk in North America and ROW. @RheumNow #EULAR2022 POS0110 https://t.co/cR6a7N2KP5
Richard Conway RichardPAConway ( View Tweet)
Dougados et al. MACE in tofa clinical programme. Baseline CV risk important. Overall MACE IR 0.38 [0.26-0.54]. MACE IR lower than in ORAL Surveillance in CV enriched pop 0.72 [0.46-1.09]. @RheumNow #EULAR2022 OP0264 https://t.co/lGTTEx0X5p https://t.co/MvD6kjkpse
Links:
Richard Conway RichardPAConway ( View Tweet)
🧫 JAKi and NK
cells activation:
JAKi and particularly TOFA impacts NK cells:
*phenotype
*function
*impairs the control of proliferation of lung cancer and lymphoma cell lines
An explanation for the increase of cancer events in ORAL surveillance?
@RheumNow #EULAR2022 OP0265 https://t.co/LzMLdzcsDU
Aurelie Najm AurelieRheumo ( View Tweet)
MACE events no diff in German RA Rabbit registry of only humans shows #baricitinib and #tofacitinib vs #TNFis @RheumNow @eular_org #EULAR2022 OP0135 https://t.co/O8iOA7jpal
Janet Pope Janetbirdope ( View Tweet)
Was ORAL Surveillance really a surprise?
Let's look post-hoc at all the other tofacitinib RCTs (ph 1-3b/4 +LTE)
Cardiovascular risk-enriched pts were always in the same MACE ballpark with tofa
ORAL Surveillance was worse, but clues were always there
OP0264 #EULAR2022 @RheumNow https://t.co/rB5SwVX2oc
David Liew drdavidliew ( View Tweet)
Montastruc et al. VigiBase study of CV and VTE events in JAKi vs TNFi. >270000 events. DECREASE in MACE ROR=0.87 [95%CI 0.80-0.95]. INCREASE in DVT: ROR=3.99 [3.15-5.04], PE: ROR=3.47 [2.90-4.13] @RheumNow #EULAR2022 OP0268 https://t.co/lUin7ciXWt https://t.co/Gr4Kvd8F7R
Links:
Richard Conway RichardPAConway ( View Tweet)
MACE in JAKi vs TNFi: did spontaneous reporting pharmacovigilance pick it?
Vigibase: MACE (really MI) & VTE signals there before the scare
Always chance regulatory warnings cause stimulated reporting
but signal here was clear before RCT-driven alerts
OP0268 #EULAR2022 @RheumNow https://t.co/hTJD1gMgyy
David Liew drdavidliew ( View Tweet)
Video: Further Considerations of the ORAL Surveillance Study
Further Considerations of ORAL Surveillance Study - this week there are new analyses and sub-analyses that further explain findings and who this data applies to. #EULAR2022
https://t.co/a2XKthtMbs https://t.co/kYNS1AesHT
Links:
Dr. John Cush RheumNow ( View Tweet)
Are TYK2 inhibitors ‘ticked’ to be part of the JAK family?
Are Tyk2 inhibitors JAK inhibitors?
Yes, no, maybe
Check out all of Dr. Janet Pope’s TYK2 Q&A.
https://t.co/IqeGqt6M4t https://t.co/kjWLVKVFP7
Links:
Dr. John Cush RheumNow ( View Tweet)
GM-CSF increased in patients with active ankylosing spondylitis, correlates with disease activity, not duration. TNFi does not affect GM-CSF levels. Could explain efficacy of JAKinibs and response for residual inflammation during TNF blockade.
@RheumNow #EULAR2022 ABST#OP0107
Robert B Chao, MD doctorRBC ( View Tweet)
