?S?????T??????

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?S?????T?????? ??T?G????? - T???????

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OS?????T??????
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?p?d?µ??????a

• ? p?? s???? ??s?? p?? d?s?e?a??e? t? ß?d?s? ?a?
  t?? a??ßas? ???µ????.
• ??????e?
• 6 s?µpt?µat??? ?? ????t??
• 3 s?µpt?µat??? ?? ?s????
• ?e???? p??ß??µa d?µ?s?a? ??e?a?

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????G????S ???????? G?? ??
??????? -?a??sa???a -?p???e?µa -?a???
?s??s? -??a?µat?sµ?? t?? ?????s??
S?S????????? -?????a -F??? -F??? -Ge?et???? (p???µ
??f?sµ?? a1-a?t?t???????, a1-??µ?t???????,
????a????? ??) -?etaß?????? d?ata?a??? (??????
a????t?da, ???d?asß?st?s?, ??????s?a) -??d???????
?????? d?ata?a??? (?pe?pa?a???e?e?d?sµ??,
a???µe?a??a)
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????t??? a?ast????µ?? pa?????te? ???d????

• ?a??sa???a
• ?e??s? t?? S.?. ?at? 5kg ? ? ?at? 50 t??
  ???d???? ??a ?? ???at?? (Framingham study)
• G?a ???e 1kg a???s? t?? ß????? ? f??t?s? t??
  ???at?? ?at? t? ß?d?s? a????e? ?at? 4-6kg
• ????pa?d???
• ????? ad??aµ?a tet?a?ef???? µ???
• ?20 ?s???? ? ? ???d???? ?at? 20-30

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?ste?a????t?da ?a? d?s?e?t?????a (Disability)

• ?? ??a??p???t??? s?s??t?s? ßa??t?t?? ????????
  e????a? ?a? d?s?e?t?????a?
• ????s? d?s?e?t?????a? ep?
• ?a??sa???a?
• ?ata????e??
• ?e????? ?????a?
• ?ap??sµat??, a??????sµ??
• ?aµ???? ??????µ???? ?a? µ??f?t???? ep?p?d??

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?S?????T??????
???d???
?st???
???????? ?µ??a?
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??T?G????? ??
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Oste?a????t?da ??ata?a?? t?? ?µ???stat????
?s????p?a? s???es?? ap?d?µ?s?? t?? ?eµe????
??s?a? t?? ???d??? (matrix)
F?s???????? ?????s? ???d????tta?a

• ?s????p?a
• a?aß?????? /?ataß?????? d??s??

• ??tta?????e?
• ????t???? pa?????te?
• F?s??? e?e??sµata

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???d????tta?a
S???es?
?p?d?µ?s?
Teµ???a ??s?a - ???te???????e? - ????a???? - ??
????a???????p??te??e?
???
Se????p??te?se?
- ????a?e??s? - St??µe??s???
matrix

• ?etaß?????
• ?s??????

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?es??aß?t?? t?? f?e?µ???? se ?ste?a????t?da
?p?peda ??tta??????? (?lisa) ap? ?? ?a?
f?s???????? a?????? ???d??
Attur MG et al. Osteoarthritis and Cartilage,
2002 Vol. 10, No. 1
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??T?G????? ?? ?st???

• ?????s? ?st???? d???d??, ?ste?f?ta
• -??s??????e?d?? a???t???? pa?????ta? (IGF)
• -?etat?ept???? a???t???? pa?????ta? ß (TGFß)
• ?p????d??e? ??ste??
• -IL-1
• -TNF-a

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??T?G????? ?????????? ?µ??a?

• F?e?µ???de?? d????se??. ? ?eµf???tta?a, µa???f??a
• ? ?eµf???tta?a e?e???p???µ??a (ep?fa?e?a??
  a?t????a e?e???p???s??, ??tta?????e? TH1)
• ? s??????? s?µß??? t??? st?? pa?????e?a de? e??a?
  epa???? ???st?

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??T?G????? ??S??????S????

• ????eta? ??? µ??? ? ???d??? a??? ?a? t? ?st???
  ?a? ? a??????? ?µ??a?
• ? s?µß??? t??? µp??e? ?a p?????e? ap? as?e?? se
  as?e?? ?a? a?????a µe t? st?d?? t?? ??s??
• S?µa?t???? ? ????? f?e?µ???d?? ??tta???????
  (IL-1, TNFa) ?a? ??

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????????S?

• ?/?
• ?RI
• CT

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T?????I? ?? S?????

• ? a?t?µet?p?s? t?? p????
• ? p?????? t?? f????? t?? a??????? ???d???
• ? d?at???s? t?? ?e?t???????t?ta? t?? ?????s??
• ? d?????s? t?? stat???? d?ata?a???

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?ste?a????t?da ????t?? ?d???e? t?? EULAR (Ann
Rheum D 59 936, 2000)

• 1. ??at?µ??e?s? ?e?ape?a?
• (?????a, ???a ??s?µata, ?pa??? f?e?µ????)
• 2. S??d?asµ?? fa?µa?e?t???? ?a? µ? fa?µa?e?t????
  µ?s??
• 3. ?s??s?, e??µ???s?, ????t??? ???eta ?a? ap??e?a
  ß????? (gt4kg)
• 4. ?s??se?? e?d??aµ?se?? tet?a?ef???? ?a?
  d?at???se?? t?? e????? t?? ????se??

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?ste?a????t?da ????t?? ?d???e? t?? EULAR (2)

• 5. ?? f??µa?? p??t?? e?????? e??a? ? pa?a?etaµ???
• 6. ?S?F (s?st?µat??? ? t?p???) se as?e?e?? p??
  de? a?tap???????ta? st?? pa?a?etaµ???
• ??t??????
• ?s?? ?pe?????? se s?ßa?? ?? ???at??, ?? ?s????
  ?a? se as?e?e?? µe ?d?a???.

Pincus T et al. Arthr. Rheum 2001
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?.S.?.F
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Cox-2 vs µ? e?d??? ?S?F

• ?s? ap?te?esµat???t?ta-µe?a??te?? ??st??
• ? ?ast?e?te????? ep?p?????
• ?aµ?a ep?pt?s? st? ?e?t?????a t?? a?µ?peta????
• ????? s?µa?t???? d?af???? st?? ?ef?????
  pa?e????e?e?

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COX-2 a?ast??e?? ?a? ?a?d?a??e?a?? s?µß?µata

• ?p?????? e?de??e?? p??a??? s?s??t?s??
• ?e??te? µe µe??d??????? p??ß??µata
• ???e? µe??te? de? ep?ßeßa?????? t?? s?s??t?s?
• ?pa?a?t?t? ? s????????s? asp?????? se as?e?e?? µe
  a???µ????? pa?????te? ???d????.
• ?p? s????????s?? ? ?ast??p??stas?a ?

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?ste?a????t?da ????t?? ?d???e? t?? EULAR (3)

• 7. ??d?a?????? ste??e?d? ep? ??e?a?
  ep?de???se?? p????
• (?d??? a? s???p???e? ?d?a?????)
• 8. ?a symptomatic slow acting drugs for
  osteoarthritis-SYSADOA
• (??????aµ???, ???d???t???, d?ase????,
  ?a????????? ???) e?d??eta? ?a t??p?p????? t?
  f?s??? p??e?a t?? ??s??

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??ase???? ?a? ?? ?s????

• ??ast???a? t?? IL-1ß
• ???a??p???µ??? d?p?? t?f?? µe??t?
• 507 as?e?e?? µe ?? ?s????
• ??ase???? (50mgX2, 3 ?t?) vs placebo
• - ep?ß??d??s? µe??s?? µesa?????? d?ast?µat??
  t?? ?s????
• - µ? s?µa?t??? ße?t??s? s?µpt?µ?t??
• (Dougados M. et al,
  Arthritis Rheum 2001)
• E?d?af???? e???µa ????? saf? ??????? s?µas?a
• ep? t?? pa???t??.

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Te???? G?????aµ??? ?a? ?? ???at??

• ?µ???sa??a??t??. ?ata??µ? st?? a????se?? µet? ap?
  per os ??????s?
• ??t?f?e?µ???d?? ?a? a?aß????? d??s?
• ??????s? 1,5 mg t? µ??a ep? 3 ?????a e??e ??
  ap?t??esµa s?µa?t??? µe??s? t?? p????, ße?t??s?
  t?? ?e?t???????t?ta? ?a? a?ast??? t?? e??tt?s??
  t?? µesa?????? d?ast?µat?? t?? ???at?? (Lancet
  2001).

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G?????aµ??? ?a? ??- ?p????s?

• S?µa?t???? pe?????sµ?? t?? ap??? a/a ??
  a?t??e?µe????? µ?s?? e?t?µ?s?? t?? ???d???
• ?a? ????? t??? pe?????sµ??? t?? µe??t?? ?
  ße?t??s? t?? p???? ?a? t?? ?e?t???????t?t??
  (???µa?a WOMAC) de? µp??e? ?a aµf?sß?t??e?

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Decrease in algofunctional index over time (mean
SEM) in the completers (n114). Maziers B et al
Journal Rheumatol 2001
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?ste?a????t?da ????t?? ?d???e? t?? EULAR (4)

• ?? ?a????????? ??? ?a? ta ???a SYSADOA
  e?d??eta? ?a e??a? ap?te?esµat??? a??? e??a?
  a???ß?, t? ?fe??? e??a? s?et??? µ???? ?a? e??a?
  ap??ß?ept? ? a?tap????s? t?? as?e???
• ?????p?ast??? ep? ep?µ???? ??????, a?ap???a?
  ?a? a?t?????????? ep?de???se??

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????? S????? (1)

• ?ste?a????t?da
• - ?? a?ast????µ?, a??? ep?d??eta?
  ße?t??s?/t??p?p???s?
• ?????? d?????s?. ??s????te?? ? p??????
  (pa??sa???a)
• ??at?µ??e?µ??? ?e?ape?a ?at? st?d?a µe f??µa?a
  ?a? ???a µ?sa

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????? S????? (2)

• ??e??e?t?µata-?????????? ???s? Cox-2 e?d???? ?S?F
• F??µa?a t??p?p???t??? t?? ??s?? µe e??a????t???
  a????? ap?te??sµata
• ?etaµ?s?e?s? ???d???, ????d?a?? ?e?ape?a (IL-1Ra)
  ?a? ??s?e? p?? e??d????? t?? a?a?????s? t??
  ???d??? (?.?. BMP) se a?????? ???????? d???µ??