Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
Professor Graham Hughes The London Lupus Centre The London Bridge Hospital
Lupus and the kidney
 
 
History
1970 <ul><li>Introduction of the (Farr)  </li></ul><ul><li>anti-DNA test </li></ul>
 
July 1969 <ul><li>Geigy Scholarship. </li></ul><ul><li>New York </li></ul>
 
Serological Changes 1909 1948 1959 1966-70 1976 1983 WR LE Cell ANA DNA ENA aPL
Antibodies predicting disease Anti-Topo1 …………… Scleroderma…………… 11 yrs Rh factor/ccp ………… RA ……………………… 14 yrs Anti-Ro & La...
Explosion of Lupus
 
 
Lupus Diagnosis Professor Hughes’ “alternative” criteria  ●  Childhood migraine ● Childhood ‘growing pains’ ● Teenage prol...
<ul><li>FAILURE </li></ul><ul><li>SUCCESS </li></ul>
Failure
Failure
Failure
Sticky Blood and Headache
 
LUPUS “- the new diabetes”
Failure
Lupus Nephritis <ul><li>Aspects of treatment </li></ul><ul><li>Failure?..... </li></ul>
What’s still bad in Lupus? <ul><li>Long time to diagnosis </li></ul><ul><li>Worldwide fluctuation in severity </li></ul><u...
Compliance? Plaquenil blood levels Ann Rheum Dis: 66,621, 2007
 
Lupus pregnancy and the kidney
Flares in pregnancy? <ul><li>Only 15% of L.N. flared in pregnancy </li></ul><ul><li>Only 2% suffered progressive fall in G...
Treatment options 2011
Antimalarials
 
Anti-malarial treatment and lupus survival <ul><li>Anti-malarial use was associated with a 38% reduction in the mortality ...
 
Thalidomide analogues?
Steroids
The Case for Conservative Management  <ul><li>Steroids   </li></ul><ul><li>Low-dose steroids in SLE </li></ul><ul><li>Hugh...
Cyclophosphamide
NIH Regime <ul><li>Used worldwide </li></ul><ul><li>Improved renal outlook </li></ul><ul><li>Toxic: infections 25% </li></...
 
The St Thomas’ Hospital Regime   (1985) <ul><li>500mg cyclo I.V. weekly x 3 </li></ul><ul><li>500mg cyclo monthly x 3-6 </...
 
Euro-Lupus Nephritis Trial Conclusion <ul><li>“…  achieves clinical results comparable to those obtained with the high dos...
New therapies for SLE <ul><li>Kaul A, D’Cruz, Hughes GRV 2006  </li></ul><ul><li>Future Rheumatology 1  235-247 </li></ul>
Expenditure for drugs for lupus <ul><li>2008 …………….. …. $1.1 billion </li></ul><ul><li>2015 ………………… $1.6 billion </li></ul>
Mycophenolate-mofetyl (cellcept ®  )
24 hour Proteinuria in Class V Lupus Nephritis Ferro et al. Abstract ACR 2003
MMF and teratogenicity <ul><li>Hypoplastic nails </li></ul><ul><li>Short 5 th  fingers </li></ul><ul><li>Diaphragmatic her...
Could MMF play a protective role in vascular disease in SLE?
Primate cardiac xenografts Inhibition of chronic vascular rejection by MMF O’Hair et al. Ann Thorac Surg, 1994
1988………………..................…..…BLyS 23 years  2011...Benlysta approval in U.K.
Belimumab BLISS 52 & 72 Results <ul><li>Reduced SLE disease activity </li></ul><ul><li>Reduced flare rates </li></ul><ul><...
Rituximab: <ul><li>Approved by FDA in 1997 for NHL </li></ul>
- but RTX in lupus trials has had a bumpy ride………………..
In defence of Rituximab ……………
Off-label use of RTX in lupus <ul><li>(27 studies) </li></ul><ul><li>Reduction in SLEDAI 59% </li></ul><ul><li>Reduction i...
RTX may even allow a “no-steroid” regime ……………..
“ No-Steroid” Regime: <ul><li>Methyl-pred 500mg+RTX 1gm  (Days 1 + 15) </li></ul><ul><li>  </li></ul><ul><li>followed by: ...
“ No-Steroid” Regime: <ul><li>Early Results. </li></ul><ul><li>  </li></ul><ul><li>29 patients </li></ul><ul><li>>2years f...
<ul><li>Words of caution………… </li></ul>
RTX and pregnancy <ul><li>Stop before pregnancy </li></ul><ul><ul><ul><ul><ul><li>Ostensen et al Rheumatology 2008,  3 , 2...
Infections ?
Ocrelizumab <ul><li>Opportunistic infections so far reported: </li></ul><ul><li>  </li></ul><ul><li>Pneumocystis jiroveci ...
JC Virus
<ul><li>FAILURE </li></ul><ul><li>SUCCESS </li></ul>
SUCCESS Eric Liddell: 1923 Olympic Gold Medallist
Success <ul><li>Recognition and Treatment of APS </li></ul>
SUCCESS Lupus and Pregnancy   50 years of progress
Success <ul><li>Fewer lupus patients are being overtreated </li></ul>
And finally …….
Don’t Believe the Textbooks!
 
Don’t Believe the Textbooks!
… eventually it usually kills  the patient...
40 years later...
 
Lupus street, London
Perseverance!
 
Upcoming SlideShare
Loading in …5
×

Nefritis Lúpica

1,226 views

Published on

Por: Dr. Graham Hughes
XIII Congreso Colombiano de Reumatologia 2011 Barranquilla

Published in: Health & Medicine
  • Be the first to comment

  • Be the first to like this

Nefritis Lúpica

  1. 1. Professor Graham Hughes The London Lupus Centre The London Bridge Hospital
  2. 2. Lupus and the kidney
  3. 5. History
  4. 6. 1970 <ul><li>Introduction of the (Farr) </li></ul><ul><li>anti-DNA test </li></ul>
  5. 8. July 1969 <ul><li>Geigy Scholarship. </li></ul><ul><li>New York </li></ul>
  6. 10. Serological Changes 1909 1948 1959 1966-70 1976 1983 WR LE Cell ANA DNA ENA aPL
  7. 11. Antibodies predicting disease Anti-Topo1 …………… Scleroderma…………… 11 yrs Rh factor/ccp ………… RA ……………………… 14 yrs Anti-Ro & La ………… Sjogrens ………………. 5 yrs Anti-DNA …………….. SLE ……………………. 11 yrs Anti-cardiolipin ………. Hughes Syndrome ….… 32 yrs ---------------------- Anti-thyroid ………….. Thyroid ………………… 10 yrs Anti-mitochondrial ….. PBC ……………………. 25 yrs
  8. 12. Explosion of Lupus
  9. 15. Lupus Diagnosis Professor Hughes’ “alternative” criteria ● Childhood migraine ● Childhood ‘growing pains’ ● Teenage prolonged ‘glandular fever’ ● Agoraphobia ● Septrin allergy ● Chronic fatigue ( ‘fibromyalgia’) ● Intermittent alopecia ● Lupus patients don’t catch colds
  10. 16. <ul><li>FAILURE </li></ul><ul><li>SUCCESS </li></ul>
  11. 17. Failure
  12. 18. Failure
  13. 19. Failure
  14. 20. Sticky Blood and Headache
  15. 22. LUPUS “- the new diabetes”
  16. 23. Failure
  17. 24. Lupus Nephritis <ul><li>Aspects of treatment </li></ul><ul><li>Failure?..... </li></ul>
  18. 25. What’s still bad in Lupus? <ul><li>Long time to diagnosis </li></ul><ul><li>Worldwide fluctuation in severity </li></ul><ul><li>No drugs licensed for Lupus </li></ul><ul><li>Poor recognition of “sticky blood” </li></ul><ul><li>Lupus awareness still poor </li></ul><ul><li>COMPLIANCE? </li></ul>
  19. 26. Compliance? Plaquenil blood levels Ann Rheum Dis: 66,621, 2007
  20. 28. Lupus pregnancy and the kidney
  21. 29. Flares in pregnancy? <ul><li>Only 15% of L.N. flared in pregnancy </li></ul><ul><li>Only 2% suffered progressive fall in GFR </li></ul>
  22. 30. Treatment options 2011
  23. 31. Antimalarials
  24. 33. Anti-malarial treatment and lupus survival <ul><li>Anti-malarial use was associated with a 38% reduction in the mortality rate. </li></ul><ul><li>Shirijo SK et al </li></ul><ul><li>A & R 2010 62 855 </li></ul>
  25. 35. Thalidomide analogues?
  26. 36. Steroids
  27. 37. The Case for Conservative Management <ul><li>Steroids </li></ul><ul><li>Low-dose steroids in SLE </li></ul><ul><li>Hughes GRV. Clin Rheum Dis 1972 </li></ul><ul><li>Low-dose methylprednisolone: equally effective, less infection </li></ul><ul><li>Badsha H et al. Semin Arthritis Rheum 2003 </li></ul>
  28. 38. Cyclophosphamide
  29. 39. NIH Regime <ul><li>Used worldwide </li></ul><ul><li>Improved renal outlook </li></ul><ul><li>Toxic: infections 25% </li></ul><ul><li> up to 30% infertility </li></ul>
  30. 41. The St Thomas’ Hospital Regime (1985) <ul><li>500mg cyclo I.V. weekly x 3 </li></ul><ul><li>500mg cyclo monthly x 3-6 </li></ul><ul><li>AZA (or MMF) </li></ul>
  31. 43. Euro-Lupus Nephritis Trial Conclusion <ul><li>“… achieves clinical results comparable to those obtained with the high dose regimen” </li></ul>Houssiau et al. A&R 2011
  32. 44. New therapies for SLE <ul><li>Kaul A, D’Cruz, Hughes GRV 2006 </li></ul><ul><li>Future Rheumatology 1 235-247 </li></ul>
  33. 45. Expenditure for drugs for lupus <ul><li>2008 …………….. …. $1.1 billion </li></ul><ul><li>2015 ………………… $1.6 billion </li></ul>
  34. 46. Mycophenolate-mofetyl (cellcept ® )
  35. 47. 24 hour Proteinuria in Class V Lupus Nephritis Ferro et al. Abstract ACR 2003
  36. 48. MMF and teratogenicity <ul><li>Hypoplastic nails </li></ul><ul><li>Short 5 th fingers </li></ul><ul><li>Diaphragmatic hernia </li></ul><ul><li>Ear deformity </li></ul><ul><li>Small jaw </li></ul><ul><li>Cleft lip and palate </li></ul><ul><li>Congenital heart defects </li></ul>
  37. 49. Could MMF play a protective role in vascular disease in SLE?
  38. 50. Primate cardiac xenografts Inhibition of chronic vascular rejection by MMF O’Hair et al. Ann Thorac Surg, 1994
  39. 51. 1988………………..................…..…BLyS 23 years 2011...Benlysta approval in U.K.
  40. 52. Belimumab BLISS 52 & 72 Results <ul><li>Reduced SLE disease activity </li></ul><ul><li>Reduced flare rates </li></ul><ul><li>Reduced prenisolone use </li></ul><ul><li>Petri et al. </li></ul><ul><li>A & R S190 2010 </li></ul>
  41. 53. Rituximab: <ul><li>Approved by FDA in 1997 for NHL </li></ul>
  42. 54. - but RTX in lupus trials has had a bumpy ride………………..
  43. 55. In defence of Rituximab ……………
  44. 56. Off-label use of RTX in lupus <ul><li>(27 studies) </li></ul><ul><li>Reduction in SLEDAI 59% </li></ul><ul><li>Reduction in BILAG 61% </li></ul><ul><li>Murray & Perry </li></ul><ul><li>Clin.Rheum 2010 </li></ul>
  45. 57. RTX may even allow a “no-steroid” regime ……………..
  46. 58. “ No-Steroid” Regime: <ul><li>Methyl-pred 500mg+RTX 1gm (Days 1 + 15) </li></ul><ul><li>  </li></ul><ul><li>followed by: MMF (2 – 3 daily) </li></ul><ul><li>No oral steroids </li></ul><ul><li>Lightstone et al 2010 </li></ul>
  47. 59. “ No-Steroid” Regime: <ul><li>Early Results. </li></ul><ul><li>  </li></ul><ul><li>29 patients </li></ul><ul><li>>2years follow-up </li></ul><ul><li>47% of patients complete remission at 1 year </li></ul><ul><li>88% of patients complete remission at 3 years </li></ul><ul><li>(No weight gain. Only 3 infections) </li></ul><ul><li>Lightstone et al 2011. </li></ul>
  48. 60. <ul><li>Words of caution………… </li></ul>
  49. 61. RTX and pregnancy <ul><li>Stop before pregnancy </li></ul><ul><ul><ul><ul><ul><li>Ostensen et al Rheumatology 2008, 3 , 28-31 </li></ul></ul></ul></ul></ul><ul><li>Crosses placenta and inhibits neonatal </li></ul><ul><li>B-lymphocyte development </li></ul><ul><ul><ul><ul><ul><li> Klink et al Clin Dev Immuno 2008 </li></ul></ul></ul></ul></ul>
  50. 62. Infections ?
  51. 63. Ocrelizumab <ul><li>Opportunistic infections so far reported: </li></ul><ul><li>  </li></ul><ul><li>Pneumocystis jiroveci pneumonia </li></ul><ul><li>Disseminated herpes zoster </li></ul><ul><li>Myco. TB and other species </li></ul><ul><li>Reactivation of hep. B. </li></ul><ul><li>Systemic candidiasis </li></ul><ul><li>CMV pneumonia and CMV retinitis </li></ul><ul><li>Histoplasmosis </li></ul>
  52. 64. JC Virus
  53. 65. <ul><li>FAILURE </li></ul><ul><li>SUCCESS </li></ul>
  54. 66. SUCCESS Eric Liddell: 1923 Olympic Gold Medallist
  55. 67. Success <ul><li>Recognition and Treatment of APS </li></ul>
  56. 68. SUCCESS Lupus and Pregnancy 50 years of progress
  57. 69. Success <ul><li>Fewer lupus patients are being overtreated </li></ul>
  58. 70. And finally …….
  59. 71. Don’t Believe the Textbooks!
  60. 73. Don’t Believe the Textbooks!
  61. 74. … eventually it usually kills the patient...
  62. 75. 40 years later...
  63. 77. Lupus street, London
  64. 78. Perseverance!

×