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Updates in lupus nephritis.pdf
The document discusses the challenges in treating lupus nephritis, emphasizing the need for early and effective therapy to prevent nephron loss. It introduces a 'sequential therapy paradigm' and highlights recent FDA-approved treatments, such as vaclosporine and benlysta, for managing difficult cases. The document advocates for a combination therapy approach and personalized treatment based on kidney condition and immune responses.
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Updates in lupus nephritis.pdf
- 1. Updates in lupusnephritis
- 2. When lupusnephritis patient come into your clinic, He/she is already lost significant number of nephrons… So we are already lagging behind the race!
- 3.
- 4. What is severelupus nephritis ? Lupus nephritis is always severe….
- 5. What do wehave for LN ? We have “the sequential therapy paradigm” : 1- Initial Induction of remission 2- Subsequent therapy to maintain remission
- 6. EULAR and Europeanrenal association (ERA), current standard of care protocol “Sequential therapy”
- 7.
- 8. What do weachieve with standard of care protocol “sequential therapy” ? -Results are unsatisfactory…! there is unmet need in LN - CRR can be achieved in only in 20 -30 % of cases.! CRR (UPCR ≤ 0.5 gm /24h , S. creatinine ≤ ULN and not increased > 15 % from baseline value & < 10 RBCs per high power field without casts ) - 20 - 25 % relapses 3-5 Y - 5 - 20 % patients ---→CKD----→ ESRD at 10 Y
- 9. To win therace against LN 1-Treat to target approach 2- Switch from “sequential ” to “combination therapy” Correct comorbidities
- 10. Treat to targetapproach Clinical target Pathological target Immunopathological target
- 11.
- 12. Target “ ≤0.7g proteinuria / 24 h achieved at 12 months”
- 14. After one yearof therapy of LN
- 15. ReBioLup at theend of the 1st year
- 17. “Window of opportunity” “The first 6 months of lupus nephritis” we have a true opportunity to achieve complete renal response (CRR). Every effort should be done to achieve 50% decrease in proteinuria during the 1st 3 m and CRR by the end of 6 m. ( ≤ 0.5 p/c ratio) Recent recommendation is to start combination therapy as early as during the1st 3 months specially in proliferative LN (III/IV).
- 18. Combination therapy ? Four new FDA approved medicine in 2020 - 2021 to treat LN on top of the well known “standard of care protocol ”
- 19. Vaclosporine (Lupkynis), newCNI inhibitor, FDA approved in Jan 2021, it is the 1st approved oral treatment in difficult to treat LN. It should be used on top of standard of care regimenwithMMF best during the 1st 6 months of therapy
- 24. Belimumab (Benlysta),1st FDAapproved biological therapy in active LN (Dec. 2020) It is full humanized monoclonal ab that binds to soluble(BLyS/BAFF), a B lymphocyte stimulator protein Benlysta doesn’t bind B cells directly, it binds to BLys-→ inhibiting the survival and differentiation of B cells.
- 27. Obinutuzumab (Gazyva), anti–CD 20 monoclonal ab much more potent B cell depletion than Rituximab Nobility study (n=125) in adults withdifficult to treat LN class III / IV : Obinutuzumab + MMF 2g + CS ≤ 10mg Placebo + MMF 2g + CS ≤ 10 mg → higher rate of CCR at one year in the Obinutuzumab arm vs Placebo The drug acts on both glomerular and tubulointerstitial disease
- 28. Anifrolumab (Saphnelo) :an anti –interferon 1 receptor Monoclonal ab, FDA approved in Aug 2021 TULIP LN phase II study (n=145) adults e proliferative LN III, IV,V: Anifrolumab (IR) (900 mg for 3 doses) + Standard of care MMF 2g + low dose steroids ≤10 mg vs Placebo + 2 gm MMF+ ≤ 10 mg CS ---→ 52 weeks Higher rate CRR (40- 45% )of patients with intensifiedregime Anifrolumab(not the basic regime),compared to placebo
- 29. How to choosetreatment----→ Look at the kidneys Extrarenal disease.. (NPSLE) Look at tubulo-interstitialtissue infiltration by immune cells lymphocytes Scattered or aggregates of lymphoidfollicles. Search for Antibody Secreting Cells (ASC)in tubulointerstitial tissue specially seen in class IV proliferativeLN
- 30. Look atglobal kidney transcriptome by compare lupus vs control fresh kidney biopsy you can find interferon gene signature (best ttt by interferon blockade) Single cell ASC transcriptomeby PCR analysis for gene involvedin proliferation: Plasmablast ----→in fresh kid biopsy in untreated LN Plasmacells ---→ are present in refractory LN cases during flares
- 31. Liquid biopsy! Welook at the ASC in the kidney and in the urine using single cells PCR analysis , the kidney and the urine are matched very well So we might use the urine as a liquid biopsy to evaluate the molecularsignature to choose one treatment overthe other