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Turns out you can directly degrade NETs. Holy smokes
NETs critical in pathology of SLE & other dx
They’ve found you can target it
Enzymatic degrader fused to albumin
Proof-of-concept: degraded a patient’s SLE manifestations in hours
Definitely one to watch
#ACR25 LB22 @RheumNow https://t.co/HVEt8wFYmI
Links:
David Liew drdavidliew ( View Tweet)
Effectiveness of b/tsDMARDs RA pts kidney dysfunction
CorEvitas RA registry 9,569 pts
Pts low eGFR = older more comorbidities less NSAIDs
Reduced eGFR = 30% less likely to achieve remission
Persists indeed of GC intake
Is it a PK/PD related issue or somehow the reflection of https://t.co/KZuvPVa6eg
Aurelie Najm AurelieRheumo ( View Tweet)
Cellular Biomarkers of Rheumatoid Arthritis https://t.co/mLYZRX9ypm
Biomarkers of RA by @jeffsparks
Lots of promising biomarkers, we need validation and hopefully translation to clinical practice.
@RheumNow
#ACR25
Nouf Al hemmadi NoufAhmedAlham2 ( View Tweet)
Microbiome signature for prediction of response to MTX in RA: Yay or Nay?
Microbiome analysis 60pts, 23 MTX NR
BL enrichment in specific species in MTX NR
Looking at the graphs though, seems to be driven by a few pts
Prediction model doesn't seem to perform greatly
Sens 88% https://t.co/1yrSXdE6DG
Aurelie Najm AurelieRheumo ( View Tweet)
Regulate-RA study, first-in-human Phase 1 study data show citrullinated protein (CitP)-targeted CAR-Tregs (SBT777101) are safe and show early efficacy in refractory RA. 67% had ≥50% joint count reduction by Week 4. A novel, non-cytotoxic approach to immune modulation for https://t.co/g153w3XVEK
Antoni Chan MD (Prof) synovialjoints ( View Tweet)
The next VEXAS, but also maybe we can treat it?
IDH1/2
Another clonal hematopoesis known to cause heme malignancy, but also some inflamm sequelae (autoinflamm-like e.g. PMR/GCA)
& you can directly inhibit it
Wow. We will hear more
#ACR25 LB21 @RheumNow
https://t.co/WL2ai5zb8Q https://t.co/Yi31xkhLO9
Links:
David Liew drdavidliew ( View Tweet)
#ACR25 Abstr#LB21 Are they novel somatic variants beyond #VEXAS in driving inflammation in undiagnosed SAID?Unbiased enrichment analysis in 265 UBA1-negative adults identified IDH1/2 hotspot mutations. Cd be used to screen esp those with cytopenia. Sorry pix not allowed @RheumNow
Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
Ph2B RCT of Rosnilimab Tcell depleter (PD-1high Tph/Tfh, Teff)
Wk 12 Primary Endpoint met
Mean change DAS28-CRP at Wk 12
SC rosnilimab 100mg Q4W -2.06
400mg Q4W -2.12
600mg Q2W -2.06
PBO -1.69
>90% peripheral and synovial depletion pathogenic T cells 28 Wk
Safety profile: https://t.co/XyVhJamFdp
Links:
Aurelie Najm AurelieRheumo ( View Tweet)
Not all RA meds are equal for the heart.
In >10K older adults w/ RA, advanced therapies lowered MACE risk (HR 0.63) vs csDMARDs, while GCs ↑ risk (HR 1.54) and undertreatment ↑ it 13-fold.
Control inflammation, protect the heart.
@RheumNow #ACR25 Abstract #2642
Jiha Lee JihaRheum ( View Tweet)
#ACR25 Abstr#LB20 At EULAR, data for Phase 3 RCT of Deucravacitinib, Tyk2-i in active #PsA showed ACR20 was met at WK16. Here, data showed sustained response through WK 52 across core domains inc. those who switched PBO->DEU. No major safety assoc. with JAK-i.A few acne @RheumNow https://t.co/tmzQMOtjev
Links:
Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
POETYK PsA-1 (one of paired deucravacitinib in PsA ph3 registration studies)
Oral med
Good outcomes
Safety very good
but the bar is very high nowadays in PsA
Questions splicing through depth of response
Definitely will find a place in therapy, but where?
#ACR25 LB19 @RheumNow https://t.co/iqmHQrMTYN
Links:
David Liew drdavidliew ( View Tweet)
POETYK PsA 1 and 2 Deucravacitinib TYK2 inhibitor Ph3 RCT
52 wks data
Deucra 336pts PBO 334pts then crossover wk 16 to 52
Pooled analysis wk 16
ACR 20 54% vs. 31%
Enthesitis reduction LEI 52% vs. 45%
Dactylics resolution 58% vs. 44%
POETYK-PsA 1 Wk 52
ACR 20 63%
ACR50 44%
PASI https://t.co/LYJbU8fYwI
Links:
Aurelie Najm AurelieRheumo ( View Tweet)
In POETYK PsA-1, deucravacitinib showed sustained efficacy through Week 52 in PsA, improving joint, skin, PROs, and radiographic progression. Safety remained favorable with no new signals. TYK2 inhibition continues to show promise. Abstract#LB20 @RheumNow #ACR25 https://t.co/sGkk062HqJ
Antoni Chan MD (Prof) synovialjoints ( View Tweet)
Questions #ACR25 LB20 to Paul Emery on rosnilimab:
Fleischmann: could be induction therapy? (Not intent, but could be)
Choy: Depth of changes with translational data
Tanaka: Safety given peresolimab ph2b here (diff epitope, membrane proximity, targeted depletion PD-1hi)
@RheumNow
David Liew drdavidliew ( View Tweet)
Mease et al. 52 week results deucravacitinib in PsA. Approx ACR20 60%, ACR50 40%, ACR70 25%. Sustained radiographic benefit. No new safety signals @RheumNow #ACR25 Abstr#LB20 https://t.co/vKqjb08mI8
Richard Conway RichardPAConway ( View Tweet)
PD-1 agonist as an induction therapy in refractory RA??
Rosnilimab ph2b:
- still responding 3mo after Rx stopped
- no difference between type of prior b/tsDMARD failure
- safety here looks good *so far*
A lot of cautious excitement in the room for this
#ACR25 LB19 @RheumNow https://t.co/CmfPlP4g0N
Links:
David Liew drdavidliew ( View Tweet)
A new approach in RA:
Rosnilimab targets & depletes PD-1–high pathogenic T cells, acting upstream of cytokine pathways. In Ph2b, all doses improved DAS28-CRP & ACR responses vs placebo, with durable efficacy & good safety.
@RheumNow #ACR25 Abstract#LB19 https://t.co/cIxi7NEu6C
Jiha Lee JihaRheum ( View Tweet)
#ACR25 Abstr#LB19 New T-cell therapy on the block! In Phase 2b RCT of #RA (~50% b/tsDMARD-IR), Rosnilimab, PD-1 agonist met its endpoint (DAS28-CRP) at WK12. Effective despite type of previous therapy. No safety concern/malignancy/death. To proceed to Phase 3 @RheumNow #ACRBest https://t.co/MecTYMpH0o
Links:
Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
Emery et al. Rosnilimab, selective T cell (PD-1high Tph/Tfh, Teff) monoclonal antibody in RA. Phase 2 RCT. 424 patients. 41% prior bDMARD. 69% CDAI LDA week 14. Week 12 ACR20 70%, ACR50 40%, ACR70 21%. @RheumNow #ACR25 Abstr#LB19 https://t.co/479q6COWvk
Richard Conway RichardPAConway ( View Tweet)
b/tsDMARD in RA + CKD (eGFR <60)
From >12K pts in CorEvitas:
- overall effective but 30% ↓ CDAI-emission (HR 0.71)
- Findings consistent across TNFi, IL-6i, ABA BCDT, JAKi
@RheumNow #ACR25 A#2640 https://t.co/UOP9ejZKoA
Jiha Lee JihaRheum ( View Tweet)
