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JAK/TYK2

lupus SLE

Tyk2 Inhibition Effective in SLE

Nov 28, 2022

Deucravacitinib, an oral, selective TYK2 inhibitor, has demonstrated efficacy in a phase II trial active systemic lupus erythematosus (SLE) patients.



The results of this phase II trial were recently presented at ACR 2022. This  phase II multinational trial enrolled 363 adults with

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Retrospective study looked at 47 adults w/ dermatomyositis treated with tofacitinib. While clinically similar, those on TOFA were were younger (53vs 61), shorter Rx duration (24 vs 53 mos);there was signif CDASI improvement. #ACR22 https://t.co/HrC1GLZQRR https://t.co/yiHsxhpiWe
Do oral JAKs in atopic dermatitis cause VTE? Meta-analysis (15 RCTs, 466 993 pts) does NOT show increased risk of VTE associated with AD & JAK inhibitors (HR 0.95) w/ low VTE incidence (0.05%) w/ JAKi and (0.03%) placebo. https://t.co/vcvW8N11cm https://t.co/N5zx0I0lrn
JAKi Regulatory Decisions - FDA, EMA, Canada New download available! https://t.co/92qbWQbMm3 https://t.co/lEjyjwxYMo
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ACR 2022 Appraisal, Praise & Critique (11.18.2022)

Nov 18, 2022

It was great to be back at an ACR annual meeting, this one in Philadelphia - Philly was great. A walking town, rich in culture, history and good places to meet and mingle. 



I loved the city, but not the convention center (not easy to navigate). 



The meeting itself was very

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Maya Buch on major adverse CV events in tofa vs TNFi. Post-hoc analysis of phase 3b/4 data looking at cohort enriched for CV events. @RheumNow #ACR22 #LateBreaking
L06 #ACR22 ORAL Surveillance Updates! Composite of all ischemic CV events and HF did NOT show difference b/w TOFA vs TNFi But, MACE numerically higher with Tofa w/ h/o ASCVD Highest CV risk in TOFA 10 mg BID, 2/2 VTE risk Most important risk is pt's individual risks @RheumNow https://t.co/jPPX7f5GRE
Does tofacitinib work better in patients with PsA and AS who smoke? Abstract #1036 #ACR22 @RheumNow 🚬519 ever smokers 🚭767 never smokers 💉In PsA only, TOF efficacy was greater in ever smokers vs. PBO ✋Overall, efficacy was generally comparable in ever v. never 🚬
Post-hoc analysis of SELECT-COMPARE showing decreased residual pain at week 12 but not week 26 cf. ADA, regardless of residual inflammation. Does this just reflect differing onset of action? @RheumNow ABST0297 #ACR22https://t.co/9WyZAN3B16 https://t.co/fAC1bLw9EB
Fleischmann et al. Safety of TYK2i Deucravacitinib in PsA/PsO in terms of labs. Really no effect on lab values other than increase in trigs. Guess this is why they don't have lab monitoring on label? @RheumNow #ACR22 Abstr#2132 https://t.co/ueIVKQc6jr https://t.co/u99QE71VQ5
Warren et al. TYK2i deucravacitinib in plaque psoriasis at 2 years. Sustained efficacy. No new safety signals seen. @RheumNow #ACR22 Abstr#2134 https://t.co/5SGKKrvwbc https://t.co/ynvfZiOrsp
New SLE Rx. Deucravitinib a TYK2i phase 2 RCT showed SRI4 endpoint. Subset of 3 mg bid was best vs 6 mg bid and 12 mg OD. Skin via CLASI-50 & other endpoints also positive. Awaiting phase III. Abst1117 #ACR22 @RheumNow https://t.co/fZI3AV5pML
Is #Tofacitinib an option in #PMR poly myalgia rheumatica? RCT of Tofa 5 mg bid vs prednisone 15 mg/d and tapering. Equal results. Needs a phase 3 trial but could be an option if needing to avoid prednisone ex osteoporosis, DM, etc. abst#1107 #ACR22 @RheumNow https://t.co/OgcgslwaB5
Kavanaugh et al. TYK2i deucravacitinib in PsA. Nice breakdown of MDA and its components over 16 weeks. MDA achieved 23-24% with deucravacitinib at 16 weeks vs 8% with placebo @RheumNow #ACR22 Abstr#2136 https://t.co/9IG8CeZzMh https://t.co/Vg8E20y7Z8
Mease et al. TYK2i Deucravacitinib in PsA. Phase 2 RCT 52 week results. PASDAS, DAPSA efficacy maintained through week 52. No new safety concerns. @RheumNow #ACR22 Abstr#1598 https://t.co/sRKkgkYtQJ https://t.co/YMXMEH3wsq
In RA pts initiating their first b/tsDMARD, Abs 1420 did not observe differences in 6- and 12-month effectiveness outcomes between ETN, ADA, and JAKi monotherapy. #ACR22 @RheumNow https://t.co/e8GA45Rrmd https://t.co/zooGxlTftO
Pike et al. Deucravactinib (TYK2i) in SLE. + on SRI(4) week 32. + SRI(4),BICLA, LLDAS, CLASI-50, swollen and tender joint counts week 48. Strange, the lowest dose (3mg bd) seems best. @RheumNow #ACR22 Abstr#1117 #ACRbest https://t.co/o4902tvZs8 https://t.co/t8oeMRGUS7
TOFA and MTX: which one to withdraw first? RCT in 100+ RA pts in remission after 1 yr, 1 yr follow-up Withdraw MTX grp: Remission 30% LDA 40% Withdraw TOFA grp: Remission 50% LDA 65% diff NS small sample 8 SAEs, 72% recoveryhttps://t.co/tMnet32TWFAbs#1586 #ACR22 @Rheumnow https://t.co/PWnkWYdlGk
#abst2132 #acr22 @rheumnow safety of Deucravacitinib Ph2PsA&ph3PSO trial: no Δ from BL in hematology, chemistry, or lipid labs. JAK 1/2/3 Effects on hem, hepatic, CPK, and cholesterol lab parameters not observed over 16 wks of DEUC at doses up to 12 mg QD & in combo w/csDMARDs. https://t.co/bjGEYp4GcJ
Plenary: Tyrosine kinase 2 (TYK2) ◦ Mediates signaling of Type I IFNs, IL-23, and IL-12 ◦ Key cytokines involved in lupus pathogenesis ◦ Deucravacitinib oral TYK2 inhibitor ◦ Phase 2 RCT in SLE showed efficacy Pike M Abs1117 https://t.co/eJhNsM02Vl #ACR22 @RheumNow https://t.co/C6JQqR1DLj
Phase 2 efficacy and safety of deucravaticinib (TYK2i) in mod-severe SLE. Met primary endpoint (SRI4) for 3mg and 6mg doses (but not 12mg). No signal for HZ but increased oral herpes. Bigger numbers will be helpful. @RheumNow #ACR22 #plenary #ACRBest https://t.co/SjW1OSQzdM
Fascinating Abs 0653 #ACR22 In vitro models show JAKis counteract celluar cytotoxicity of HCQ in a human retinal pigment epithelial cell line and podocytes. Possible new way to dec. retinopathy/nephropathy? @RheumNow https://t.co/5NtLoDzjKG https://t.co/GG2R03xAes
Ab1117 #ACR22 Deucravacitinib: TYK2 inhibitor in active SLE? 363 pt P2, double-blind PBO-controlled 48 wk study DEUC 3 mg BID, 6 BID, 12 QB vs PBO: At 32wk: DEUC 3BID & 6BID > PBO, sustained across all groups at 48wk. AEs: similar bw PBO and DEUC. No VTE @RheumNow #ACRBest https://t.co/uamJe05odq
Tofa 5 mg BID successful in treating refractory uveitis in reducing inflammation and reducing steroid dosage. Abs 1041 #ACR22 @RheumNow https://t.co/dtAEhW7dEG https://t.co/Xbw2iEsYHh
Kahlenberg @Kahlenberglab et al. TYK2i deucravacitinib in SLE. Clinical efficacy (figure). Deucravacitinib suppressed IFN production, IFN-responsive gene expression, IFN-inducible proteins, B cell markers,serological biomarkers. @RheumNow #ACR22 Abstr#1000 https://t.co/zzkoPLOlSR https://t.co/znyG8N5pJ2
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