#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) #IVIG IN DM : 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 Liftiflimab -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) Gout # 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 -benefit: 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 |
Rheumatology >