Donald L Kimpel MD March 28 2015 Sentara Medical Center LFADMV The Many features and flavors of Systemic Lupus 11 ACR criteria ACR SLICC Plaquenil Eye Testing Diabetes and Lupus ID: 808698
Download The PPT/PDF document "SLE Update “What’s New In Lupus”" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
SLE Update“What’s New In Lupus”Donald L Kimpel, MD.
March 28, 2015
Sentara Medical Center
LFA-DMV
Slide2The Many features and
“flavors” of Systemic Lupus
11 ACR criteria
Slide3Slide4ACR ~= SLICC
Slide5Plaquenil Eye Testing.
Slide6Diabetes and LupusPlaquenil may decrease risk of developing DiabetesMetformin and 2-deoxy-glucose inhibit glucose metabolism, and both
reduce T cell activation
decrease autoantibodies
Improve kidney function
…in mice. Ref: Morel et al, Sci Transl Med 2015.
Slide7Immune Dysfunction in SLEB cell hyperactivity T and B cell signaling abnormalities
Defective clearance of Antibody-Antigen immune complexes
Cytokine abnormalities:
“Interferon signature”
Slide8Treatment: New Ways with Old Drugs
Slide9New Treatment for LupusBelimumab (Benlysta)First new drug for lupus in 50 years.
An engineered human protein biologic.
Indications
Active lupus
Autoantibody positiveNo severe active kidney or central nervous system lupus.
Slide10Benlysta: Administration and Mechanism of ActionHuman monoclonal antibody.
Administered intravenously.
Every 2 weeks for the first 3 doses
Then every 4 weeks.
Inhibits BlyS (B lymphcyte Stimulator); also known as BAFF.This limits a stage of B cell maturation, so that memory B cells (which make antibodies) don’t develop.
Slide11Benlysta MOA
Slide12B Cell Subsets
Cancro
MP et al, J
Clin
Invest 2009: 119: 1066-73
.
Slide13Anti-B cell Development Drugs and TargetsBelimumab (Benlysta) : Blys
/ BAFF
Atacicept
: TACIBlisibimod: Blys
/ BAFFTabalumab: Blys / BAFF membrane bound and freeWithdrawn by Eli Lilly
Slide14Anti-B cell Surface molecule Drugs and TargetsRituxmab: CD20
Ocrelizumab
: CD20
Epratuzumab: CD22
Slide15Rituximab in Lupus
Slide16What causes lupus?GenesEnvironmentLack of resistance genes
Slide17Laboratory markers of LupusFc receptor type may indicate susceptibility or severity.
Slide18Type I IFNElevated type I IFN levels in serum of many SLE patients
IFN treatment
can
induce autoantibodies and SLE-like symptomsIFN-
a treatment of NZB/W F(1) mice results in severe SLEGene expression profiles show “interferon signature”
Slide19Targeting InterferonSifalimumab (MedImmune
/
AstraZeneca)
Monoclonal antibodyIIb study completed, met endpoints of percent responders
Slide20TreatmentNSAIDs, COX-2 inhibitorsPrednisone (steroids), preferably low dose, oralAzathioprine
Cellcept
/
mycophenylate mofeteil (MMF);
MyforticCyclophosphamide: IV or orallyBelimumab (Benlysta)Rituximab (
Rituxan)IVIg, plasmapheresis, High dose IV steroids