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JAKs and Other Drugs in PMR
This has been an interesting ACR meeting in terms of PMR updates. I would argue that we are still far too wedded to glucocorticoids only in the management of PMR. Yes, some patients will do fine with just glucocorticoids but we persist far too long with a glucocorticoid only strategy in others who clearly need an alternative as glucocorticoid adverse events multiply.
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Say Goodbye to Methotrexate in PMR?
For decades, glucocorticoids (GCs) have formed the backbone of polymyalgia rheumatica (PMR) management.
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The Case for JAKi in PMR
Dr. David Liew abstract 0858, Baricitinib in Early Polymyalgia Rheumatica (BACHELOR Study), presented at #ACR24.
https://t.co/NLF75PuMOb https://t.co/FpUUdbtrwf
Dr. John Cush RheumNow ( View Tweet)
Say Goodbye to Methotrexate in PMR?
Despite mixed results on its clinical efficacy in three previous randomised controlled trials (RCTs)1-3, methotrexate is considered the most widely used GC sparing agent. #ACR24
https://t.co/Q5Sw9dvYqJ https://t.co/jvEmg6aPcq
Dr. John Cush RheumNow ( View Tweet)
@drceowen @TheLancetRheum @RheumNow Efficacy in newly diagnosed & established PMR is not necessarily interchangeable
different treatment paradigm
?different immunologically
Many other diseases have different Rx for induction vs maintenance, early dx vs established.
Having said that: doesn't look great for MTX. https://t.co/89lByaYdYq
David Liew drdavidliew ( View Tweet)
Lot said about #ACR24 ABST1697:
MTX in newly diagnosed PMR, neg RCT
Many have said no hope for MTX in PMR now
Agree doesn't bode well
However, MTX may still have role in established PMR
@drceowen & I have made that call a priori @TheLancetRheum https://t.co/ywCJc0zHzC
@RheumNow https://t.co/JUXk2tDNyR
Links:
David Liew drdavidliew ( View Tweet)
I've shared some thoughts on @RheumNow on methotrexate, tocilizumab, and baricitinib in PMR based on #ACR24 https://t.co/WXiW1nLN4k
Richard Conway RichardPAConway ( View Tweet)
Harkins @DrTrishHarkins et al. Impact of AC joint OA in PMR. 67% of PMR have AC joint OA. Those who do have worse pain and fatigue scores. @RheumNow #ACR24 Abstr#1974 https://t.co/vAqVuQ5Jzm https://t.co/zx5MMtWdBE
Links:
Richard Conway RichardPAConway ( View Tweet)
Does adding a Clofutriben (HSD-1 inhibitor) w/ prednisone minimize the risks of steroid toxicities in #PMR patients?
VS placebo, PMR patients who received Clofutriben + Prednisone had substantial reductions in bone, lipid, and glycemic control parameters
@RheumNow #ACR24
Akhil Sood MD AkhilSoodMD ( View Tweet)
Would be helpful for us (and pts) to better understand rimmunotherapy agent specific risk on subsequent GCA/PMR
AFTRER propensity matching of >7k pt on combo nivolumab/ipilimumab compared to pembrolizumab:
- PMR RR 3.8x N/I vs. P
- no diff in GCA risk
@RheumNow #ACR24 https://t.co/IF4Gh7Cumd
Brian Jaros, MD Dr_Brian_MD ( View Tweet)
Chevet et al. What happens when you withdraw tocilizumab after 6 months in PMR? Follow up of SEMAPHORE study. 80.8% relapsed! Median time to relapse 15 weeks. @RheumNow #ACR24 Abstr#1698 https://t.co/9pJ88C05V2
Richard Conway RichardPAConway ( View Tweet)
Sarilumab is better than #MTX in #PMR
Reminder #RCT of #MTX in #PMR was a NEGATIVE #trial #1697
60 % #sarilumab in #RWE could d/c
#Prednisone after failure of initial #pred #Rx >1yr pred prior vs 40% MTX
Comparative effectiveness sari v MTX
#1700 #ACR24 @ACRheum @RheumNow https://t.co/4YXIBz0OK7
Links:
Janet Pope Janetbirdope ( View Tweet)
When you stop 🛑 #TCZ #tocilizumab at
6 months of #Rx in #PMR
RELAPSES are V high
DON’T stop #Toci in PMR too
Early
Rapid and frequent flares
#ACR24 @RheumNow @ACRheum #1698 https://t.co/IX5EJOcIY5
Janet Pope Janetbirdope ( View Tweet)
Which subsets of GCA pt might benefit most from upadacitinib?
Sub-analysis from SELECT-GCA presented today:
💥Both relapsing and refractory disease
💥Pt w hx of PMR
💥Non-smokers
💥No hx ischemic eye dz
In general, most subgroups still favor UPA
@RheumNow #ACR24 Abst 1695 https://t.co/pX5hcX4TmR
Brian Jaros, MD Dr_Brian_MD ( View Tweet)
#Methotrexate is a dud in #PMR for benefit above #glucocorticoids !
#RCT MTX25mg/wk + Pred 15
Mg/d tapered to 0 at 1 yr vs #Prednisone + placebo same taper
NO BENEFIT from #MTX
#1697 #ACR24 @ACRheum @RheumNow
As FYI
Poster at #EULAR observed
#Leflunomide better than #MTX https://t.co/RepBmOKIsA
Links:
Janet Pope Janetbirdope ( View Tweet)
Harkins @DrTrishHarkins et al. PROs predict relapse in PMR. pVAS, HAQ health status, FACIT-F all positive predictors. Interestingly PHQ-9 negative predictor. @RheumNow #ACR24 Abstr#1238 https://t.co/kj4WgmI0oq https://t.co/xLDzRZvxoA
Links:
Richard Conway RichardPAConway ( View Tweet)
It's always so dispiriting to see PMR patients rack up steroid side effects in front of your eyes.
(the intense motivation to do better than pred for our PMR patients)
#ACR24 @SattuiSEMD @RADoctor ABST0975 @RheumNow https://t.co/FTsvrTIt2F
David Liew drdavidliew ( View Tweet)
Harkins @DrTrishHarkins et al. Novel diagnostic cytokines in treatment naive PMR. Elevations CXCL-9 (100%), MCP-1 (93%), IL-17A (83%), vs TNF (7%) and IL-6 (67%) @RheumNow #ACR24 Abstr#0881 https://t.co/DbYOn81QJH https://t.co/3eyre00D5d
Links:
Richard Conway RichardPAConway ( View Tweet)
🤵♂️Results from BACHELOR
➡️34 PMR pts
➡️18 BARI, 16 PBO
➡️Primary endpoint: CRP PMR-AS≤10 w/o oral GC rescue from W0 to 12
78% BARI pts reached primary endpoint vs 13% PBO
No new safety signals
BARI 4mg 12W, then 2mg 12W➡️36W low disease activity in PMR
Ab0858 #ACR24 @RheumNow
Mrinalini Dey DrMiniDey ( View Tweet)
JAKs in PMR? "BACHELOR" study randomized 34pts to BARI vs PLBO
Despite small sample, significant benefit at 12 wks (CRP PMR-AS < 10) for bari (78%) vs. PLBO (13%)
Useful, but not for getting regulatory approval. Should have gone straight to phase 3!
#ACR24 @RheumNow Abstr#0858 https://t.co/mmMs6c3AYC
Links:
Mike Putman EBRheum ( View Tweet)
