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Abst 2694:
Post-hoc analysis of Phase 2 PAISLEY SLE trial examined impact of deucravacitinib on renal dysfunction
🔹 Plasma proteins a/w ↑ BILAG renal score and ↓ UPCR --> reduced by WK 32
🔹 Biomarkers inversely related to eGFR were reduced with deucra vs PBO
@RheumNow #ACR25 https://t.co/6CvmQ9lCfS
Links:
Akhil Sood MD, MS AkhilSoodMD ( View Tweet)
Deucravacitinib (TYK2) in PsA from POETYK trials
Improved ACR20 at wk16 (NNT ~5), less benefit for ACR70 (NNT ~20)
Steady improvements during open label extension (all pts received drug)
Would expect approval for PsA soon... where will this fit in your approach?
@RheumNow https://t.co/325h2hf0AE
Links:
Mike Putman EBRheum ( View Tweet)
Thank you @drdavidliew & @DrLauraCoates ❤️ for highlighting our work. Super-responders (some were IS-Free) do exist with rituximab in #SLE Abstr#1525 @RheumNow https://t.co/S4mMAYInfT
Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
Autologous CAR-Treg in RA, without any lymphodepletion preRx
Early data from ph1, single dose
Good initial response, stopped RA Rx, but some rebound
Clearly work ongoing but excitement re:
- CAR-Treg
- RA as target dx
- no lymphodepletion
@minnakohlermd #ACR25 LB23 @RheumNow https://t.co/azmlFNU02R
Links:
David Liew drdavidliew ( View Tweet)
REGULATE RA SBT-77-701
Engineered Treg cell in Refractory RA population
6patients
Safety and tolerability: No DLT, CRS or ICANS
Efficacy
Reduction >50% in TJC and SJC
67% reduction of DAS-CRP >=2
stained up to wk 24
Impressive in pts for whom it works, yet a couple seem to https://t.co/lQAQABPhg0
Links:
Aurelie Najm AurelieRheumo ( View Tweet)
#ACR25 Abstr#LB23 Phase 1 trial in 5 refractory #RA of SBT777101, a novel autologous CAR-Treg (without the need for lymphodepletion) showed promising efficacy and safety signal. No DLT, CRS or ICANS. Looking forward to larger data and in other RMDs @RheumNow https://t.co/YyGMSHjA3z
Links:
Md Yuzaiful Md Yusof Yuz6Yusof ( View Tweet)
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)
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)
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)
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)
