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ACR 2022

#Clinical Science Year in Review (Carol Langford)

#JAKi : Review article LUi C, A and R 2021
Tofacitinib: all Jak 1,2,3 (T for Three)
Baricitinib: Both 1,2 (B for both)
Upadacitinib: 1 (U for Uno or 1)
Deucravacitinib: TYK2 i

#5 new approval for JAKi
Tofacitibinb: AS
Upa: PsA, AS, nr-axSpA
Deucravacitinib: Psoriasis, PsA, SLE (not FDA approved, but in publication)

#IL-6 : JAK1 and 2

#Type 1 IFN: Jak1 and Tyk 2

#FDA Approval 
JAKi - 5 new approval as noted above
IL-23i - Risankizumab  for PsA (previously approved was Guselkumab)

#Bimekisumab: IL17Aand IL17F inhibitor 
 (nrAxSpA, AS, PsA, PsO) 

NEJM 2022, IVIG 

2gm / kg every  4weeks  for 16 week 

TIS (composite of 6 factors)

79% vs 44 % 
-6 VTE 

# Anti-CD19 Car T cell therapy in refractory SLE 
Mackensen, A 
Nat Med 2022 

Essentially, leads to CD19 depleted B cells. 
5 patients of were studied. 
All immunomodulatory studies stopped in 2 months
1 patient requires: Tocilizumab

3 phase 2 study for SLE 

#Phase 2 
-targets Blood Dendritic cells Antigen 2 (BDCA2)
NEJM: Cutaneous SLE, Other SLE 
-met the primary endpoint

#Phase 2 Obinutuzumab
B cell target (against CD20)
-met primary endpoints

#Phase 2 
Iberomide (decreases B cell activity y and type 1 IFN)

# Pegloticase (MIRROR trial, A and R, 2022) + MTX 
-will this decrease antibody 
-MTX used for 4 weeks before Pegloticase was added 

71 vs 39 % Treatment vs Placebo

FDA: expanded the label to include co-administration with MTX 

# Basic science rear in Review  by Dr. John Varga (Uni of Michigan)
Basic science review 

# TLR7 gene gain in function mutation leads to severe SLE 
Endosomal member of the pattern recognition 
It makes TLR 7 receptors more sensitive to recognize nuclear acid 

Very strong IFN signature 

TLR 7 is targeted by Hydroxychloroquin ??  or new 

#elelvated CD38 CD8 T cell leads to increased infection due to depletion of NAD leads to impaired Cytotoxic T cell , thus severe infection
- reducing CD38 affects mitochondrial fitness and cytotoxic T-cell response against viral infection , infection much better controlled 
-subset of patient has increased CD38

#Assessing lesions and normal skin areas in SLE shows 
-the different pattern was seen 
-but the IFN pathway was upregulated in both lesional and non-lesional skin, mostly in the stromal cells (keratinocytes and fibroblasts were expressing a high levels of IFN signature)

#Is Fibrosis reversible by immunotherapy using cytotoxic T cells 
-antigen expressed during embryogenesis but suppressed and then reappeared during the period of fibrogenesis 
-identify and target these antigens 
-ADAM12 and Gli 1 (Markers of Fibrogenic cells)
-developed a series of vaccines selective for these targets  
-showed prevention of liver fibrosis, lung fibrosis mouse model 
-were even able to reverse fibrosis 

# RA patients are TNF super producer
What is the mechanism of TNF super production in RA 
-showed it was synovial T cells than the circulating T cells