Tumor Necrosis Factor-· ·ÓÙ·ÁˆÓÈÛÙ¤˜:
H NEA E¶OXH ™THN £EPA¶EIA
TøN Oº£A§MIKøN º§E°MONøN
EÈÛËÁËÙ‹˜
¡. ª·ÚÎÔÌȯÂÏ¿Î˘
40Ô ¶ANE§§HNIO Oº£A§MO§O°IKO ™YNE¢PIO
Tumor Necrosis Factor-· ·ÓÙ·ÁˆÓÈÛÙ¤˜:
H NEA E¶OXH ™THN £EPA¶EIA
TøN Oº£A§MIKøN º§E°MONøN
¡. ª·ÚÎÔÌȯÂÏ¿Î˘ 1, π. ¶··Â˘ı˘Ì›Ô˘ 1, Ã. £ÂÔ‰ÔÛ›Ô˘ 1,
¶. ª·Ï¿ÌÔ˜ 1, ¶. £ÂÔ‰ÔÛÈ¿‰Ë˜ 2, ∆. ∫Ô˘Ú‹˜ 1
1. ∆Ì‹Ì· ºÏÂÁÌÔÓÒÓ Î·È ∞ÓÔÛÔÏÔÁ›·˜ OÊı·ÏÌÒÓ. OÊı·ÏÌÔÏÔÁÈ΋ ∫ÏÈÓÈ΋
°.¡.∞ıËÓÒÓ «°.°ÂÓÓËÌ·Ù¿˜»
2. µ’ OÊı·ÏÌÔÏÔÁÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ
¤ÎÊÚ·ÛË ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘ (ICAM-1) ÛÙ· ÂÓ‰ÔıËÏȷο ·ÌÊÈ‚ÏËÛÙÚÔÂȉÈο ·ÙÙ·Ú· Î·È ·›˙ÂÈ ÂӉ¯Ô̤ӈ˜ ·ÚÈÔ ÚfiÏÔ ÛÙË
‰È·Ù·Ú·¯‹ ÙˆÓ ·ÈÌ·ÙÔ·ÌÊÈ‚ÏËÛÙÚÔÂȉÈÎÒÓ ÊÚ·ÁÌÒÓ Ô˘ ·Ú·ÙËÚÂ›Ù·È ÛÙȘ Ú·ÁÔÂȉ›Ùȉ˜.
∂ÍÔ˘‰ÂÙ¤ÚˆÛË Ù˘ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ ÙÔ˘ ∆¡F ÎÏÈÓÈο ÚÔηÏ›
·ÔÂÓÂÚÁÔÔ›ËÛË Ù˘ ¤ÎÊÚ·Û˘ ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ, Ì›ˆÛË Ù˘
ÛÙÚ·ÙÔÏÔÁ›·˜ ÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ¿ÚˆÓ ·Ô ÙÔ ·›Ì· ÛÙË ı¤ÛË Ù˘
ÊÏÂÁÌÔÓ‹˜, ÌÂȈ̤ÓË ·ÁÁÂÈÔÁ¤ÓÂÛË Ì¤Ûˆ ÙÔ˘ ·˘ÍËÙÈÎÔ‡ ·ÁÁÂÈ·ÎÔ‡ ÂÓ‰ÔıËÏÈ·ÎÔ‡ ·Ú¿ÁÔÓÙ· (VEGF) ηıÒ˜ Î·È ÌÂÙ·‚ÔϤ˜ ÙˆÓ
¯ËÌÂÈÔÎÈÓÒÓ, ÙˆÓ ÚˆÙÂÈÓÒÓ ÔÍ›·˜ Ê¿Û˘ Î·È Ù˘ ‰È·ÂÚ·ÙfiÙËÙ·˜
ÙˆÓ ·ÁÁ›ˆÓ. ∏ ‰È·›ÛÙˆÛË ˘„ËÏÒÓ Û˘ÁÎÂÓÙÚÒÛÂˆÓ TNF ÛÙÔÓ ÔÚfi
‹/Î·È ÛÙÔ ˘‰·ÙÔÂȉ¤˜ ˘ÁÚfi ·ÛıÂÓÒÓ Ì ڷÁÔÂȉ›Ùȉ·, ·ÌÊÈ‚ÏËÛÙÚÔÂȉÈ΋ ·ÁÁÂÈ›Ùȉ· Î·È Û˘Ì·ıËÙÈ΋ ÔÊı·ÏÌ›· ˘Ô‰ËÏÒÓÂÈ ÙÔÓ
ÂȉÈÎfi ÚfiÏÔ Ô˘ ·›˙ÂÈ Ô TNF ÛÙȘ ÂÓ‰ÔÊı¿ÏÌȘ ÊÏÂÁÌÔÓ¤˜ ηÈ
‰ÈηÈÔÏÔÁ› ‚¿ÛÈÌ· ÙËÓ ¯Ú‹ÛË Ê·ÚÌ¿ÎˆÓ Ô˘ ÛÙÔ¯Â‡Ô˘Ó ÂÍÂȉÈÎÂ˘Ì¤Ó· ÛÙÔÓ TNF ÛÙËÓ ıÂÚ·›· ÙˆÓ Ú·ÁÔÂȉÈÙ›‰ˆÓ.
∂‰Ò Î·È 10 ¯ÚfiÓÈ·, ÔÈ ·ÓÙ·ÁˆÓÈÛÙ¤˜ ÙÔ˘ Tumor Necrosis Factor-·
(TNF-·) ¤Î·Ó·Ó ÙËÓ ÂÌÊ¿ÓÈÛË ÙÔ˘˜ ˆ˜ ÌÈ· Ó¤· ÔÌ¿‰· ıÂÚ·¢ÙÈÎÒÓ
·Ú·ÁfiÓÙˆÓ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ·˘ÙÔ¿ÓÔÛˆÓ Û˘ÛÙËÌ·ÙÈÎÒÓ
ÓÔÛËÌ¿ÙˆÓ. ¶Ôχ ÁÚ‹ÁÔÚ· ·ԉ›¯ÙËÎÂ Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·
ÙÔ˘˜ ÛÙËÓ ÚÂ˘Ì·ÙÔÂȉ‹ ·ÚıÚ›Ùȉ·, ÙËÓ Ó·ÓÈ΋ ȉÈÔ·ı‹ ·ÚıÚ›Ùȉ·, ÙËÓ ÓfiÛÔ Crohn, ÙËÓ ·ÁÎ˘ÏˆÙÈ΋ ÛÔÓ‰˘Ï›Ùȉ·, ÙËÓ „ˆÚÈ·ÛÈ΋ ·ÚıÚ›Ùȉ· Î·È ÙËÓ „ˆÚ›·ÛË Î·È ¤Ï·‚·Ó ¤ÁÎÚÈÛË ÁÈ· ¯ÔÚ‹ÁËÛË
·fi ÙÔÓ ∂ıÓÈÎfi OÚÁ·ÓÈÛÌfi ¢È·¯Â›ÚÈÛ˘ ∆ÚÔÊ›ÌˆÓ Î·È º·Ú̿ΈÓ
(FDA) ÙˆÓ ∏¶∞ . Ÿˆ˜ ·Ó·ÌÂÓfiÙ·Ó Ë ¯Ú‹ÛË ·˘ÙÒÓ ÙˆÓ ÂÎÏÂÎÙÈÎÒÓ
Î·È ‰˘Ó·ÌÈÎÒÓ ·Ó·ÛÙÔϤˆÓ Ù˘ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ÂÍÂÚÁ·Û›·˜ ÂÂÎÙ¿ıËΠ·Ì¤Ûˆ˜ Î·È ÛÙËÓ ıÂÚ·›· ÙˆÓ ÛÔ‚·ÚÒÓ ÔÊı·ÏÌÈÎÒÓ
ÊÏÂÁÌÔÓÒÓ, Ô˘ Û¯ÂÙ›˙ÔÓÙ·È fi¯È ÌfiÓÔ Ì ٷ ·Ú·¿Óˆ Û˘ÛÙËÌ·ÙÈο ÓÔÛ‹Ì·Ù·, ·ÏÏ¿ Î·È ÙËÓ ÓfiÛÔ ∞‰·Ì·ÓÙÈ¿‰Ë-Behçet, ÙËÓ Û·ÚÎÔ›‰ˆÛË, ÙËÓ ÓfiÛÔ Vogt-Koyanagi-Harada, ÙËÓ ÓfiÛÔ Graves,
fiˆ˜ Â›Û˘ ÙËÓ «‰›ÎËÓ Î˘ÓËÁÂÙÈÎÒÓ ¯fiÓ‰ÚˆÓ» ¯ÔÚÈÔ·ÌÊÈ‚ÏËÛÙÚÔÂȉÔ¿ıÂÈ·, ÙËÓ ÔÏ˘ÂÛÙȷ΋ ¯ÔÚÈÔÂȉ›Ùȉ· Î·È ·ÓÚ·ÁÔÂȉ›Ùȉ·, ÙÔ Û‡Ó‰ÚÔÌÔ ‰È¿¯˘Ù˘ ˘Ô·ÌÊÈ‚ÏËÛÙÚÔÂȉÈ΋˜ ›ÓˆÛ˘,
ÙËÓ pars planitis Î·È ÙȘ ·ÓıÂÎÙÈΤ˜ ȉÈÔ·ı›˜ Ú·ÁÔÂȉ›Ùȉ˜ ‹
ÛÎÏËÚ›Ùȉ˜.
OÈ ·ÓÙ›-∆¡F ·Ú¿ÁÔÓÙ˜
¶ÚÔ˜ ÙÔ ·ÚfiÓ ÙÚ›˜ ·ÓÙ›-TNF ·Ú¿ÁÔÓÙ˜ Â›Ó·È ÂÌÔÚÈο ‰È·ı¤ÛÈÌÔÈ.
∆Ô etanercept (Enbrel®), ÌÈ· ·Ó·Û˘Ó‰˘·Ṳ̂ÓË ÚˆÙ½ÓË Û˘Á¯ÒÓ¢Û˘, ·ÔÙÂÏÔ‡ÌÂÓË ·fi ‰‡Ô ÂÍˆÎ˘ÙÙ¿ÚÈÔ˘˜ ·ÓıÚÒÈÓÔ˘˜ ˘ԉԯ›˜ p 75 Ô˘ ÂÓÒÓÔÓÙ·È Ì ÙÔ ÙÌ‹Ì· Fc Ù˘ IgG. ∏ ÚˆÙ½ÓË
Û˘ÏÏ·Ì‚¿ÓÂÈ ÌfiÓÔ ÙÔ ‰È·Ï˘Ùfi, ¯ˆÚ›˜ Ó· ÂËÚ¿˙ÂÈ ÙÔ ÌÂÌ‚Ú·Ó҉˜ ∆¡F .∏ ËÌ›ÛÂÈ· ˙ˆ‹ ÙÔ˘ etanercept Â›Ó·È 3 Ì 5 Ë̤Ú˜ ηÈ
ÂÓ›ÂÙ·È ˘Ô‰fiÚÈ· ÛÙË ‰fiÛË ÙˆÓ 25 mg ‰‡Ô ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·.
∆Ô infliximab (Remicade®), ¤Ó· ¯ÂÈÌÂÚÈÎfi ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷
Ô˘ Û˘Ó‰¤ÂÈ ¤Ó· ÌÂÙ·‚ÏËÙfi ÙÌ‹Ì· ÔÓÙÈÎÔ‡ ÂȉÈÎfi ÁÈ· ÙÔ ∆¡F-· ÌÂ
¤Ó· ÙÌ‹Ì· Fc Ù˘ ·ÓıÚÒÈÓ˘ IgG. ∆Ô ·Óٛۈ̷ ·‰Ú·ÓÔÔÈ›
ÙfiÛÔ ÙËÓ ‰È·Ï˘Ù‹ fiÛÔ Î·È ÙËÓ ÌÂÌ‚Ú·ÓÒ‰Ë ÌÔÚÊ‹ ÙÔ˘ TNF. ∏
ËÌ›ÛÂÈ· ˙ˆ‹ ÙÔ˘ infliximab Â›Ó·È 10 Ë̤Ú˜. ∏ ıÂÚ·›· ¯ÔÚËÁ›ٷÈ
ÂÓ‰ÔÊϤ‚È· ÁÈ· ‰‡Ô ÂÚ›Ô˘ ÒÚ˜ ÛÙË ‰fiÛË ÙˆÓ 5 mg/kg ÙË ÚÒÙË
‚‰ÔÌ¿‰· Ô˘ Â·Ó·Ï·Ì‚¿ÓÂÙ·È ‰‡Ô Î·È ¤ÍÈ Â‚‰ÔÌ¿‰Â˜ ·ÚÁfiÙÂÚ·
Î·È ÌÂÙ¿ οı ¤ÍÈ ‹ ÔÎÙÒ Â‚‰ÔÌ¿‰Â˜.
∆Ô adalimumab (Humira®) ¤Ó· Û˘ÓıÂÙÈÎfi ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷
ηı·Ú¿ ·ÓıÚÒÈÓÔ. ∂ȉڿ Â›Û˘ Î·È ÛÙȘ ‰‡Ô ÌÔÚʤ˜ ÙÔ˘ TNF.
∏ ËÌ›ÛÂÈ· ˙ˆ‹ ÙÔ˘ adalimumab Â›Ó·È 15-19 Ë̤Ú˜ Î·È ¯ÔÚËÁ›ٷÈ
˘Ô‰fiÚÈ· 40mg οı ÌÈ· ‹ ‰‡Ô ‚‰ÔÌ¿‰Â˜.
O ÚfiÏÔ˜ ÙÔ˘ ∆¡F ÛÙȘ ÔÊı·ÏÌÈΤ˜ ÊÏÂÁÌÔÓ¤˜
O ∆¡F Â›Ó·È Ì›· ÏÂÈÔÙÚfiÔ˜ ΢ÙÙ·ÚÔΛÓË Ô˘ ·Ú¿ÁÂÙ·È Î˘Ú›ˆ˜
·fi ÌÔÓÔ·ÙÙ·Ú·/Ì·ÎÚÔÊ¿Á· Î·È ∆-ÏÂÌÊÔ·ÙÙ·Ú· Î·È Û ÌÈÎÚfiÙÂÚÔ ‚·ıÌfi ·Ô Ô˘‰ÂÙÂÚfiÊÈÏ· Î·È ÛÈÙ¢ÙÈο ·ÙÙ·Ú· (mast cells)
ˆ˜ ·¿ÓÙËÛË Ïԛ̈͢ ‹ ·ÓÔÛÔÏÔÁÈ΋˜ ‚Ï¿‚˘. ∫·È ÔÈ ‰‡Ô ÌÔÚʤ˜
ÙÔ˘ TNF, Ë ‰È·Ï˘Ù‹ Î·È Ë ÌÂÌ‚Ú·Ó҉˘, ÚÔ¿ÁÔ˘Ó ÙËÓ ÊÏÂÁÌÔÓ‹
›Ù ¿ÌÂÛ· ̤ۈ ΢ÙÙ·ÚÔÙÔÍÈÎfiÙËÙ·˜, ›Ù ¤ÌÌÂÛ· ̤ۈ Ú‡ıÌÈÛ˘
Ù˘ ·Ú·ÁˆÁ‹˜ ¿ÏÏˆÓ ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ, Ù˘ ·ÂÏ¢ı¤ÚˆÛ˘ ÂÓÂÚÁÔ‡ Ô͢ÁfiÓÔ˘ Î·È ÓÈÙÚˆ‰ÒÓ, ÙˆÓ ÌÂÙ·ÏÏÔÚˆÙÂ˚Ó·ÛÒÓ, ÙˆÓ ¯˘ÌÔÎÈÓÒÓ, ÙˆÓ ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘ Î·È ÙˆÓ ·ÁÁÂÈÔÁÂÓÂÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ.
¶Ï‹ıÔ˜ ÂÈÚ·Ì·ÙÈÎÒÓ ‰Â‰ÔÌ¤ÓˆÓ ·Ô‰ÂÈÎÓ‡Ô˘Ó fiÙÈ Ô TNF ·›˙ÂÈ
ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Ù˘ ÂÓ‰ÔÊı¿ÏÌÈ·˜ ÊÏÂÁÌÔÓ‹˜,
Ô˘ ıˆÚÂ›Ù·È ·˘ÙÔ¿ÓÔÛÔ ÓfiÛËÌ· ‰È·ÌÂÛÔÏ·‚Ô‡ÌÂÓÔ Ì¤Ûˆ ÂȉÈÎÒÓ ¤Ó·ÓÙÈ ÙˆÓ ·ÓÙÈÁfiÓˆÓ T-‚ÔËıËÙÈÎÒÓ (Th1) ΢ÙÙ¿ÚˆÓ Î·È ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ‚Ï¿‚Ë ÙˆÓ ÔÊı·ÏÌÈÎÒÓ ÈÛÙÒÓ Ì¤Ûˆ Ì·ÎÚÔÊ¿ÁˆÓ Î·È ∆-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ™ÙȘ ÂÈÚ·Ì·ÙÈΤ˜ Ú·ÁÔÂȉ›Ùȉ˜ ‰È·ÈÛÙÒÓÂÙ·È ·˘ÍË̤ÓË ÂÓ‰ÔÊı¿ÏÌÈ· Û˘ÁΤÓÙÚˆÛË ÙÔ˘ ∆¡F, ÂÓÒ
¤ÓÂÛË TNF ÛÙÔ ˘·ÏÔÂȉ¤˜ ÂÈÚ·Ì·Ùfi˙ˆˆÓ ÚÔηÏ› ·˘ÙÔ¿ÓÔÛË
Ú·ÁÔÂȉ›Ùȉ·. ∞ÓÙÈı¤Ùˆ˜ Ë ÂÍÔ˘‰ÂÙ¤ÚˆÛË ÙÔ˘ TNF Ì ÙË ¯Ú‹ÛË
ÂÓfi˜ ‰È·Ï˘ÙÔ‡ TNF ˘Ô‰Ô¯¤·, ÚÔηÏ› ·Ó·ÛÙÔÏ‹ Ù˘ ‰Ú·ÛÙËÚÈfiÙËÙ·˜ ÙˆÓ Ì·ÎÚÔÊ¿ÁˆÓ, Û˘ÓÂÈÛʤÚÔÓÙ·˜ ÛÙËÓ Ì›ˆÛË Ù˘ ηٷÛÙÚÔÊ‹˜ ÙˆÓ ÊˆÙÔ¸Ô‰Ô¯¤ˆÓ. ∂›Û˘ Ô ∆¡F Úԉȷı¤ÙÂÈ ÛÙËÓ
OÈ ·ÓÙ›-∆¡F ·Ú¿ÁÔÓÙ˜ ÛÙȘ ÔÊı·ÏÌÈΤ˜ ·ı‹ÛÂȘ
ª¤¯ÚÈ ÙÔÓ ∞Ú›ÏÈÔ ÙÔ˘ 2007, 203 ‰ËÌÔÛȇÛÂȘ ÛÙËÓ ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›· ·Ó·Ê¤ÚÔÓÙ·È ÛÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙˆÓ ·ÓÙ›-∆¡F
168
E§§HNIKH Oº£A§MO§O°IKH ETAIPEIA
·Ú·ÁfiÓÙˆÓ ÛÙȘ ÔÊı·ÏÌÈΤ˜ ÊÏÂÁÌÔÓ¤˜. ∆· Ê¿Ú̷η ·˘Ù¿ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û ÂÚÈÙÒÛÂȘ ÊÏÂÁÌÔÓ‹˜ Ô˘ ·ÂÈÏÂ›Ù·È Ë fiÚ·ÛË,
ÏfiÁˆ Ù˘ ¤ÓÙ·Û˘, Ù˘ ¯ÚÔÓÈfiÙËÙ·˜ ‹ ÙÔ˘ ˘ÔÙÚÔÈ¿˙ÔÓÙÔ˜ ¯·Ú·ÎÙ‹Ú· ÙÔ˘˜, Î·È Â›Ó·È ·ÓıÂÎÙÈΤ˜ ÛÙȘ ÎÏ·ÛÛÈΤ˜ ıÂÚ·›˜ (ÎÔÚÙÈ˙fiÓË ‹/Î·È ·ÓÔÛÔηٷÛÙ·ÏÙÈο). ¶·ÚfiÏÔ Ô˘ ‰ÂÓ ˘¿Ú¯Ô˘Ó ·ÎfiÌ·
ÚÔÔÙÈΤ˜, Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜, Ë ÂÎÙ›ÌËÛË Û‹ÌÂÚ· Â›Ó·È fiÙÈ
Ë ¯Ú‹ÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ ·˘ÙÒÓ ÌÔÚ› Ó· ÂÈÙ‡¯ÂÈ fiÏÔ˘˜ ÙÔ˘˜
ÛÙfi¯Ô˘˜ ÌÈ·˜ ÂÈÙ˘¯Ô‡˜ ıÂÚ·›·˜: Ó· ·ÓÙÈÌÂÙˆ›ÛÂÈ fiÛÔ Á›ÓÂÙ·È
ÈÔ ÁÚ‹ÁÔÚ· ÙËÓ ÔÍ›· Ê¿ÛË Ù˘ ÊÏÂÁÌÔÓ‹˜, Ó· ÂÌÔ‰›ÛÂÈ ‹ ÙÔ˘Ï¿¯ÈÛÙÔÓ Ó· ÌÂÈÒÛÂÈ ÛËÌ·ÓÙÈο ÙÔÓ ·ÚÈıÌfi ÙˆÓ ˘ÔÙÚÔÒÓ Î·È
Ù¤ÏÔ˜ Ó· ÂÌÔ‰›ÛÂÈ ÙËÓ ÂÌÊ¿ÓÈÛË ÌË ·Ó·ÛÙÚ¤„ÈÌˆÓ ‚Ï·‚ÒÓ ÛÙÔ˘˜
ÔÊı·ÏÌÈÎÔ‡˜ ÈÛÙÔ‡˜.
‰Â˜, ¯ÔÚ‹ÁËÛË infliximab Û ·ÛıÂÓ›˜ Ì ڷÁÔÂȉ›Ùȉ·, ·ÓıÂÎÙÈ΋ ·ÎfiÌ· Î·È ÛÂ Û˘Ó‰˘·ÛÌfi ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ, ·˙·ıÂÈÔÚ›Ó˘
Î·È Î˘ÎÏÔÛÔÚ›Ó˘, ÌÂÈÒÓÂÈ ÙÔÓ ·ÚÈıÌfi ÙˆÓ ˘ÔÙÚÔÒÓ ÛÂ
‚·ıÌfi ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈÎfi, ·˘Í¿ÓÂÈ ÙËÓ ÙÂÏÈ΋ ÔÙÈ΋ Ô͇ÙËÙ·
Î·È ÂÏ·ÙÙÒÓÂÈ ÙËÓ ·Ó¿ÁÎË ¯ÔÚ‹ÁËÛ˘ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ.
¶Ôχ ÚfiÛÊ·Ù· ÔÌ¿‰· ÂȉÈÎÒÓ ·fi fiÏÔ ÙÔÓ ÎfiÛÌÔ Î·Ù·Ï‹Í·ÌÂ
ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ ÙÔ infliximab (2-3ÂÓ‰ÔÊϤ‚Ș ÂÁ¯‡ÛÂȘ)
Ú¤ÂÈ Ó· ¯ÔÚËÁÂ›Ù·È ˆ˜ ıÂÚ·›· ‰È¿ÛˆÛ˘ Û ÛÔ‚·Ú¤˜ ÔÍ›˜
Ô›ÛıȘ Ú·ÁÔÂȉ›Ùȉ˜ Ô˘ ·ÂÈÏÂ›Ù·È Ë fiÚ·ÛË. ∂ÓÒ ÌÔÚ› Ó·
¯ÚËÛÈÌÔÔÈËı› ÛÂ Û˘Ó¯‹ ¯ÔÚ‹ÁËÛË (ÁÈ· ‰‡Ô ¤ÙË) ˆ˜ ıÂÚ·›·
Û˘ÓÙ‹ÚËÛ˘ Û Ô›ÛıȘ Ú·ÁÔÂȉ›Ùȉ˜ ·ÓıÂÎÙÈΤ˜ Û ·ÓÔÛÔηٷÛÙ·ÏÙÈο.
ŸÏ· Ù· ‰Â‰Ô̤ӷ ̤¯ÚÈ Û‹ÌÂÚ· Û˘ÓËÁÔÚÔ‡Ó fiÙÈ ÙÔ infliximab
˘ÂÚÙÂÚ› ÛËÌ·ÓÙÈο Û ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ¤Ó·ÓÙÈ ÙÔ˘
etanercept, ·ÎfiÌ· Î·È ÛÙȘ ÂÚÈÙÒÛÂȘ Û˘ÛÙËÌ·ÙÈÎÒÓ ÓÔÛËÌ¿ÙˆÓ,
Ô˘ ÌfiÓÔ ÙÔ ‰Â‡ÙÂÚÔ Â›Ó·È ÂÁÎÂÎÚÈ̤ÓÔ (.¯. ¡Â·ÓÈ΋ π‰ÈÔ·ı‹˜
∞ÚıÚ›Ùȉ·). ∞Ó Î·È Ô ·ÚÈıÌfi˜ ÙˆÓ ÌÂÏÂÙÒÓ ÁÈ· ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ adalimumab Â›Ó·È ÚÔ˜ ÙÔ ·ÚfiÓ ÌÈÎÚfi˜, Ê·›ÓÂÙ·È fiÙÈ
Î·È ÙÔ ÌÔÓÔÎψÓÈÎfi ·˘Ùfi ·Óٛۈ̷ Â›Ó·È Â›Û˘ ‰Ú·ÛÙÈÎfi ÛÙÔÓ
¤ÏÂÁ¯Ô ÙˆÓ ÂÓ‰ÔÊı¿ÏÌÈˆÓ ÊÏÂÁÌÔÓÒÓ.
∆ÔÓ π·ÓÔ˘¿ÚÈÔ ÙÔ˘ 2007 ÛÙËÓ π·ˆÓ›· ‰fiıËΠ¤ÁÎÚÈÛË ÁÈ· ÙËÓ
¯ÔÚ‹ÁËÛË Infliximab Û ·ÛıÂÓ›˜ Ì ÓfiÛÔ ∞‰·Ì·ÓÙÈ¿‰Ë-µehçet ηÈ
Ô›ÛıÈ· Ú·ÁÔÂȉ›Ùȉ·, Ô˘ ‰ÂÓ ·ÓÙ·ÔÎÚ›ÓÂÙ·È ÛÙËÓ Û˘Ì‚·ÙÈ΋
ıÂÚ·›·.
¡Â·ÓÈ΋ π‰ÈÔ·ı‹˜ ∞ÚıÚ›Ùȉ·
∞fi ÙËÓ ÂÔ¯‹, Ô˘ Ô Reif A Î·È Û˘ÓÂÚÁ¿Ù˜ Î·È Ë Smith JR ηÈ
Û˘ÓÂÚÁ¿Ù˜, ÁÈ· ÚÒÙË ÊÔÚ¿ ‰ËÌÔÛ›Â˘Û·Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÙÔ˘˜
ÁÈ· ÙËÓ ‰Ú·ÛÙÈÎfiÙËÙ· ÙˆÓ ·ÓÙ›-TNF ÛÙËÓ Ú·ÁÔÂȉ›Ùȉ· ÙËÓ Û¯ÂÙÈ˙fiÌÂÓË Ì ¡Â·ÓÈ΋ π‰ÈÔ·ı‹ ∞ÚıÚ›Ùȉ·, Ï‹ıÔ˜ ÌÂÏÂÙÒÓ ¤‰ÂÈÍ·Ó fiÙÈ
Ë Ì·ÎÚÔ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛË infliximab ‹ adalimumab ÌÔÚ› Ó·
ÂϤÁÍÂÈ Û fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Ï‹Úˆ˜ ‹ ¤ÛÙˆ ÌÂÚÈÎÒ˜ ÙËÓ
ÔÊı·ÏÌÈ΋ ÓfiÛÔ Û ·ÓÙ›ıÂÛË Ì ÙÔ etanercept Ô˘ Ë ·ÔÙ˘¯›· ÙÔ˘
ÊÙ¿ÓÂÈ Û ÔÛÔÛÙfi 70%. ∏ ¯ÔÚ‹ÁËÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ ·˘ÙÒÓ ÌÂÈÒÓÂÈ Â›Û˘ ÛËÌ·ÓÙÈο ÙȘ ÂÈÏÔΤ˜ fiˆ˜ ÙÔ ÁÏ·‡ÎˆÌ· ηÈ
‚ÂÏÙÈÒÓÂÈ ÙËÓ ·ÛÊ¿ÏÂÈ· ÙˆÓ ¯ÂÈÚÔ˘ÚÁÈÎÒÓ ÂÂÌ‚¿ÛˆÓ. ∂Ó ÙÔ‡ÙÔȘ ‰ÂÓ Ê·›ÓÂÙ·È Ó· ÌÂÈÒÓÂÙ·È Ô Î›Ó‰˘ÓÔ˜ ÂΉ‹ÏˆÛ˘ ÁÈ· ÚÒÙË
ÊÔÚ¿ Ú·ÁÔÂȉ›Ùȉ·˜ Û ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ·ÓÙ›-TNF ÁÈ· ÙËÓ
·ÚıÚ›Ùȉ· ÙÔ˘˜.
™ÙÔ ∆Ì‹Ì· ºÏÂÁÌÔÓÒÓ Î·È ∞ÓÔÛÔÏÔÁ›·˜ OÊı·ÏÌÒÓ Ù˘ OÊı·ÏÌÔÏÔÁÈ΋˜ ∫ÏÈÓÈ΋˜ ÙÔ˘ °.¡. ∞ıËÓÒÓ «°. °ÂÓÓËÌ·Ù¿˜» ¤¯Ô˘Ì ¯ÔÚËÁ‹ÛÂÈ Ì¤¯ÚÈ Û‹ÌÂÚ· ·ÓÙ›-TNF ·Ú¿ÁÔÓÙ˜ Û 84 ·ÛıÂÓ›˜ Ì ÛÔ‚·Ú‹ ÔÊı·ÏÌÈ΋ ÊÏÂÁÌÔÓ‹. OÈ 42 ·ÛıÂÓ›˜ ¤·Û¯·Ó ·fi ÓfiÛÔ ∞‰·Ì·ÓÙÈ¿‰Ë-Behçet, ÔÈ 17 ·fi ȉÈÔ·ı‹ Ú·ÁÔÂȉ›Ùȉ·, ÔÈ 14 ·fi HLAB27+ ÛÔÓ‰˘Ï·ÚıÚÔ¿ıÂÈ·, ÔÈ 7 ·fi ¡Â·ÓÈ΋ π‰ÈÔ·ı‹ ∞ÚıÚ›Ùȉ·
Î·È ÔÈ 4 ·fi ȉÈÔ·ı‹ ÛÎÏËÚ›Ùȉ·. ™Â 10 ·ÛıÂÓ›˜ ¯ÔÚËÁ‹ıËΠ·Ú¯Èο etanercept, ·ÏÏ¿ Û 7, ÏfiÁˆ ·‰˘Ó·Ì›·˜ Ó· ÂÏÂÁ¯ı› Ë ÔÊı·ÏÌÈ΋ ÊÏÂÁÌÔÓ‹, ·Ó·ÁηÛًηÌ ӷ ·ÏÏ¿ÍÔ˘Ì ıÂÚ·›· Î·È Ó· ¯ÔÚËÁ‹ÛÔ˘Ì infliximab (4 ·ÛıÂÓ›˜) ‹ adalimumab (3 ·ÛıÂÓ›˜). ™Â ¤Ó·
·ÛıÂÓ‹ ·fi ÙÔ˘˜ 74 Ô˘ ¤Ï·‚·Ó ÂÍ ·Ú¯‹˜ infliximab ‰ÂÓ ˘‹ÚÍÂ
·ÓÙ·fiÎÚÈÛË Î·È ¯ÔÚËÁ‹ıËΠadalimumab. ™Â 21 ·ÛıÂÓ›˜ Ô ÛÙfi¯Ô˜ Ù˘ ıÂÚ·›·˜ ‹Ù·Ó Ë ÁÚ‹ÁÔÚË ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÊÏÂÁÌÔÓ‹˜
Î·È Û 63 Ô Ì·ÎÚÔ¯ÚfiÓÈÔ˜ ¤ÏÂÁ¯Ô˜ ÙˆÓ ˘ÔÙÚÔÒÓ. ∆ÂÏÈο ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ ıÂÚ·›·˜ ÎÚ›ıËΠˆ˜ ·ÓÂÈÙ˘¯¤˜ Û ¤Ó· ÌfiÓÔ ·ÛıÂÓ‹.
¶ÚfiÛıÈ· Ú·ÁÔÂȉ›Ùȉ· Û¯ÂÙÈ˙fiÌÂÓË Ì ÔÚÔ·ÚÓËÙÈΤ˜ ÛÔÓ‰˘Ï·ÚıÚÔ¿ıÂȘ Î·È ÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù· ÙÔ˘ ÂÓÙ¤ÚÔ˘
™‹ÌÂÚ· fiÏÔÈ ÔÈ ·Ó·ÛÙÔÏ›˜ TNF ıˆÚÔ‡ÓÙ·È ÚÒÙ˘ ÁÚ·ÌÌ‹˜ Ê¿Ú̷η Û ÂÚÈÙÒÛÂȘ ·ÁÎ˘ÏˆÙÈ΋˜ ÛÔÓ‰˘Ï›Ùȉ·˜ ‹ „ˆÚÈ·ÛÈ΋˜
·ÚıÚ›Ùȉ·˜, Ô˘ ‰ÂÓ ·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È Ì ÌË ÛÙÂÚÔÂȉ‹ ·ÓÙÈÊÏÂÁÌÔÓÒ‰Ë. ∂Ó ÙÔ‡ÙÔȘ ÌfiÓÔ ÙÔ infliximab Û ̷ÎÚÔ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛË
Ê·›ÓÂÙ·È Ó· ÌÂÈÒÓÂÈ ÙËÓ Â›ÙˆÛË ÂΉ‹ÏˆÛ˘ ÚfiÛıÈ·˜ Ú·ÁÔÂȉ›Ùȉ·˜. ∞Ó Î·È Ë ¯ÔÚ‹ÁËÛË ÌÈ·˜ ÌfiÓÔ ‰fiÛ˘ infliximab Û ‚·ÚȤ˜
ÈÚȉÔ΢ÎÏ›Ùȉ˜ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ¿ÌÂÛË ‚ÂÏÙ›ˆÛË ÙˆÓ ÎÏÈÓÈÎÒÓ Û˘ÌÙˆÌ¿ÙˆÓ Ì ÁÚ‹ÁÔÚË Ì›ˆÛË Ù˘ ·ÓÙ›‰Ú·Û˘ ·Ô ÙÔ
ÚfiÛıÈÔ ı¿Ï·ÌÔ, ÌÈ· Ù¤ÙÔÈ· ·ÓÙÈÌÂÙÒÈÛË ‰ÂÓ ıˆÚÂ›Ù·È ··Ú·›ÙËÙË, ·ÊÔ‡ Û˘ÓÙËÚËÙÈÎfiÙÂÚ˜ ıÂÚ·›˜ Â›Ó·È Â›Û˘ ·ÔÙÂÏÂÛÌ·ÙÈΤ˜. ∆Ô ›‰ÈÔ ÈÛ¯‡ÂÈ Î·È Û ÚfiÛıȘ Ú·ÁÔÂȉ›Ùȉ˜ Û¯ÂÙÈ˙fiÌÂÓ˜ Ì HLA-B27¯ˆÚ›˜ Û˘ÛÙËÌ·ÙÈΤ˜ ÂΉËÏÒÛÂȘ.
¡fiÛÔ˜ ∞‰·Ì·ÓÙÈ¿‰Ë-µehçet
∏ ÓfiÛÔ˜ ∞‰·Ì·ÓÙÈ¿‰Ë-µehçet ·ÔÙÂÏ› ›Ûˆ˜ ÙËÓ ÓfiÛÔ fiÔ˘ ÙÔ
infliximab ¤¯ÂÈ ÙËÓ ÌÂÁ·Ï‡ÙÂÚË ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·.
∆Ô 2001 Ë ÔÌ¿‰· Ì·˜ ‰ËÌÔÛ›Â˘Û ÁÈ· ÚÒÙË ÊÔÚ¿ ÙËÓ Ù·¯Â›· ηÈ
·ÔÙÂÏÂÛÌ·ÙÈ΋ ‰Ú¿ÛË ÙÔ˘ infliximab ÛÙËÓ ÔÍ›· Ê¿ÛË ÛÔ‚·Ú‹˜
Ô›ÛıÈ·˜ Ú·ÁÔÂȉ›Ùȉ·˜. ∏ ¿ÌÂÛË Î·Ù·ÛÙ·ÏÙÈ΋ ‰Ú¿ÛË ‹Ù·Ó fiÓÙˆ˜
ÂÓÙ˘ˆÛȷ΋ Î·È ‰È·ÈÛÙÒıËΠ·fi ÙÔ ÚÒÙÔ 24ˆÚÔ. ŒÎÙÔÙ ¿Óˆ
·fi 60 ‰ËÌÔÛȇÛÂȘ ¤¯Ô˘Ó ÂȂ‚·ÈÒÛÂÈ ÂΛӷ Ù· ÚÒÙ· ·ÔÙÂϤÛÌ·Ù·. ªÂÙ¿ ·fi ÌÈ· ÌfiÓÔ ‰fiÛË Ê·ÚÌ¿ÎÔ˘ Ë ÊÏÂÁÌÔÓ‹ ÛÙÔÓ
ÚfiÛıÈÔ ı¿Ï·ÌÔ ˘Ô¯ˆÚ› ÂÓÙÂÏÒ˜ ̤۷ Û ϛÁ˜ Ë̤Ú˜, Ë
˘·Ï›Ùȉ· ÌÂÙ¿ ÙËÓ ÚÒÙË Â‚‰ÔÌ¿‰·, Ë ·ÌÊÈ‚ÏËÛÙÚÔÂȉ›Ùȉ· ÌÂÙ¿
2 ‚‰ÔÌ¿‰Â˜, ÂÓÒ ·ÁÁÂÈ›Ùȉ· Î·È Î˘ÛÙÂÔÂȉ¤˜ Ô›‰ËÌ· Ù˘ ˆ¯Ú¿˜
ÌÂÙ¿ ·fi 3 ‚‰ÔÌ¿‰Â˜. ªÂ ‚¿ÛË ÙËÓ ÂÌÂÈÚ›· Ì·˜ ÙÔ infliximab
‰Ú· ÈÔ ÁÚ‹ÁÔÚ· Û ۇÁÎÚÈÛË Ì οı ¿ÏÏË ÌÔÚÊ‹ ıÂÚ·›·˜
ÛÙËÓ ÔÍ›· Ê¿ÛË Ù˘ ÔÊı·ÏÌÈ΋˜ ÓfiÛÔ˘ ∞‰·Ì·ÓÙ›¿‰Ë-µehçet,
·ÎfiÌ· Î·È ÙȘ ÈÔ ÂÓÙ·ÙÈΤ˜, fiˆ˜ Â›Ó·È Ë ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË
˘„ËÏÒÓ ‰fiÛÂˆÓ ÎÔÚÙÈÎÔÂȉÒÓ (1.000mg SoluMedrol®) ‹ Ë ÂÓ‰Ô¸·ÏÔÂȉÈ΋ ¤Á¯˘ÛË ÙÚÈ·ÌÎÈÓÔÏfiÓ˘ (4mg Kenacort®).
™Â ÂÚÈÙÒÛÂȘ ÓfiÛÔ˘ Crohn Ì Â͈ÂÓÙÂÚÈΤ˜ ÂΉËÏÒÛÂȘ ÌfiÓÔ ÙÔ
infliximab ıˆÚÂ›Ù·È ˆ˜ ÚÒÙ˘ ÁÚ·ÌÌ‹˜ Ê¿ÚÌ·ÎÔ Î·È ÌÔÚ› Ó·
ÂϤÁÍÂÈ ÁÚ‹ÁÔÚ· ÌÈ· ÔÍ›· Ú·ÁÔÂȉ›Ùȉ·.
™·ÚÎÔ›‰ˆÛË
™Ù· ÎÔÎÎȈ̷ÙÒ‰Ë Û˘ÛÙËÌ·ÙÈο ÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù·, fiˆ˜ Ë
Û·ÚÎÔ›‰ˆÛË, ÌfiÓÔ Ù· ÌÔÓÔÎψÓÈο ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙ› ÙÔ˘ TNF
Ê·›ÓÂÙ·È Ó· Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈο. ∂Ô̤ӈ˜ Ë ¯Ú‹ÛË infliximab,
Û ÂÚÈÙÒÛÂȘ ÔÊı·ÏÌÈ΋˜ Û·ÚÎÔ›‰ˆÛ˘ ·ÓıÂÎÙÈΤ˜ ÛÙȘ
ηıÈÂڈ̤Ó˜ ıÂÚ·›˜ Ì ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ Î·È ·ÓÔÛÔηٷÛÙ·ÏÙÈο, ÌÔÚ› Ó· ÂϤÁÍÂÈ ÙËÓ ÊÏÂÁÌÔÓ‹ Î·È Ó· ·ÔÙÂϤÛÂÈ
∂ÈÚÔÛı¤Ùˆ˜ Ë Ì·ÎÚÔ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛË infliximab ¤¯ÂÈ ıÂÙÈ΋ Â›‰Ú·ÛË ÛÙËÓ ‡ÊÂÛË Ù˘ ÓfiÛÔ˘. Ÿˆ˜ ¤‰ÂÈÍÂ Ë ÔÌ¿‰· Ì·˜ -Î·È ÛÙË
Û˘Ó¤¯ÂÈ· ÔÏϤ˜ ÔÌ¿‰Â˜ Û˘ÁÁڷʤˆÓ- Ë Û˘Ó¯‹˜, ·Ó¿ 8 ‚‰ÔÌ¿-
169
40Ô ¶ANE§§HNIO Oº£A§MO§O°IKO ™YNE¢PIO
ÙÔ˜ (Ï¢¯·ÈÌ›·, ·Ó΢ÙÙ·ÚÔÂÓ›·), Â¤ÎÙ·ÛË ÙˆÓ ÂÛÙÈÒÓ Û ·ÛıÂÓ›˜ Ì ÛÎÏ‹Ú˘ÓÛË Î·Ù¿ Ͽη˜, Âȉ›ӈÛË Ù˘ ηډȷ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ¤ˆ˜ ı·Ó¿ÙÔ˘ Â› ηډȷ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ Î·È Ó¢ÌÔÓÈ΋
ÂÌ‚ÔÏ‹. ¶ÂÚ›Ô˘ ÔÈ ÌÈÛÔ› ·Ô ÙÔ˘˜ ·ÚÚÒÛÙÔ˘˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó
ıÂÚ·›· Ì infliximab Î·È ÙÔ 10% ·˘ÙÒÓ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ıÂÚ·›·
Ì etanercept ·Ó·Ù‡ÛÛÔ˘Ó ·ÓÙÈ˘ÚËÓÈο ·ÓÙÈÛÒÌ·Ù· ÛÙË ‰È¿ÚÎÂÈ·
Ù˘ ıÂÚ·›·˜. ∏ ÂÌÊ¿ÓÈÛË fï˜ Û˘ÛÙËÌ·ÙÈÎÔ‡ ÂÚ˘ıËÌ·ÙÒ‰Ô˘˜
χÎÔ˘ Â›Ó·È Û¿ÓÈ·. ∏ ÈÔ Û˘¯Ó‹ ·ÓÂÈı‡ÌËÙË ÂÓ¤ÚÁÂÈ· ·fi ÙËÓ
¯ÔÚ‹ÁËÛË ÙÔ˘ infliximab Â›Ó·È Ë ÂΉ‹ÏˆÛË ÛÔ‚·Ú‹˜ ·ÏÏÂÚÁÈ΋˜
·ÓÙ›‰Ú·Û˘. ∏ ·ÚÁ‹ ¤Á¯˘ÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ (Û 3 ÒÚ˜) ÂÏ·¯ÈÛÙÔÔÈ› ÙÔÓ Î›Ó‰˘ÓÔ ·ÏÏÂÚÁ›·˜. ™Â ·Ú·ÙÂٷ̤Ó˜ ıÂÚ·›˜ ÌÂ
infliximab, ÏfiÁˆ Ù˘ ‡·Ú͢ ÌË ·ÓıÚÒÈÓÔ˘ ÙÌ‹Ì·ÙÔ˜ ÛÙÔ ÌfiÚÈÔ
ÙÔ˘ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÂÌÊ·ÓÈÛÙÔ‡Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÂÚÈÔÚ›˙ÂÙ·È Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ ÌÂ
ÙËÓ ¿ÚÔ‰Ô ÙÔ˘ ¯ÚfiÓÔ˘ Û ÔÛÔÛÙfi Ô˘ ÊÙ¿ÓÂÈ ÙÔ 50% ÙˆÓ ·ÛıÂÓÒÓ. ∏ Ù·˘Ùfi¯ÚÔÓË ¯Ú‹ÛË ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÔ‡, ÌÔÚ› Ó· ¢ÓÔ‹ÛÂÈ ÙËÓ ·ÓÔ¯‹ ÙÔ˘ ÚÔ˚fiÓÙÔ˜ ÂÚÈÔÚ›˙ÔÓÙ·˜ ÙËÓ ·Ú·ÁˆÁ‹ ·˘ÙÒÓ
ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Î·È Ó· ‚ÂÏÙÈÒÛÂÈ ÙÔ ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ·.
ÂÓ·ÏÏ·ÎÙÈ΋ ıÂÚ·¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË.
π‰ÈÔ·ı‹˜ ‰È¿ÌÂÛË Î·È Ô›ÛıÈ· Ú·ÁÔÂȉ›Ùȉ·
™ÙËÓ ‚È‚ÏÈÔÁÚ·Ê›· ˘¿Ú¯Ô˘Ó ϤÔÓ ÔÏϤ˜ ‰ËÌÔÛȇÛÂȘ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙËÓ ‰Ú·ÛÙÈÎfiÙËÙ· ÙˆÓ ·Ó·ÛÙÔϤˆÓ TNF Û ȉÈÔ·ı›˜
ÔÊı·ÏÌÈΤ˜ ÊÏÂÁÌÔÓ¤˜ ‹ Û ÎÏÈÓÈΤ˜ ÔÓÙfiÙËÙ˜ ¿ÁÓˆÛÙ˘ ·ÈÙÈÔÏÔÁ›·˜, ÂÓ ÙÔ‡ÙÔȘ fiϘ ·ÊÔÚÔ‡Ó Û ÌÈÎÚ¤˜ ÛÂÈÚ¤˜ ·ÛıÂÓÒÓ ‹ Û ÛÔÚ·‰ÈΤ˜ ÂÚÈÙÒÛÂȘ. ¶·Ú¿ ÙËÓ ‰˘ÛÎÔÏ›· Ó· ÂÎÙÈÌËı› Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙˆÓ ·ÓÙ›-∆¡F ÛÙË ıÂÚ·›· ÙˆÓ ‰È¿ÌÂÛˆÓ Î·È Ô›ÛıÈˆÓ Ú·ÁÔÂȉ›ÙȉˆÓ, ˘¿Ú¯ÂÈ ÈÛ¯˘Ú‹ ÂÔ›ıËÛË fiÙÈ Û ÛÔ‚·Ú¤˜,
·ÂÈÏÔ‡Û˜ ÙËÓ fiÚ·ÛË ‹ ·ÓıÂÎÙÈΤ˜ Û ¿ÏϘ ıÂÚ·›˜ ÂÚÈÙÒÛÂȘ, Ù· Ê¿Ú̷η ·˘Ù¿ ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ˆ˜
ıÂÚ·›· ‰È¿ÛˆÛ˘ ‹ ˆ˜ ıÂÚ·›· Û˘ÓÙ‹ÚËÛ˘. ∏ «‰›ÎËÓ Î˘ÓËÁÂÙÈÎÒÓ ¯fiÓ‰ÚˆÓ» ¯ÔÚÈÔ·ÌÊÈ‚ÏËÛÙÚÔÂȉÔ¿ıÂÈ· (Birdshot
chorioretinopathy), ÙÔ Û‡Ó‰ÚÔÌÔ ‰È¿¯˘Ù˘ ˘·ÌÊÈÌ‚ËÛÙÚÔÂȉÈ΋˜
›ÓˆÛ˘, ÙÔ Û‡Ó‰ÚÔÌÔ ÔÏ˘ÂÛÙȷ΋˜ ¯ÔÚÈÔÂȉ›Ùȉ·˜ Î·È ·ÓÚ·ÁÔÂȉ›Ùȉ·˜ Î·È Ë pars planitis Â›Ó·È Î¿ÔÈ· ·fi Ù· ÔÊı·ÏÌÈο ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù· Ô˘ ÙÔ infliximab ı· ÌÔÚÔ‡Û ӷ ¯ÔÚËÁËı› ÂÈÙ˘¯Ò˜ ·Ó ¿ÏϘ ıÂÚ·›˜ ¤¯Ô˘Ó ·ÔÙ‡¯ÂÈ.
°ÂÓÈÎÒ˜ Ë ¯ÔÚ‹ÁËÛË ·ÓÙ›-∆¡F ÔÊ›ÏÂÈ Ó· Á›ÓÂÙ·È Ì ÌÂÁ¿ÏË ÚÔÛÔ¯‹ Û ·ÛıÂÓ›˜ Ì ıÚÔÌ‚ˆÙÈ΋ ‰È¿ıÂÛË Î·È ·ÓÙÂӉ›ÎÓ˘Ù·È ÛÂ
·ÛıÂÓ›˜ Ì ·ÔÌ˘ÂÏÈÓˆÙÈ΋ ÓfiÛÔ, ηډȷ΋ ·ÓÂ¿ÚÎÂÈ· ηÈ
ÚfiÛÊ·ÙË Ïԛ̈ÍË. ™Â ·ÛıÂÓ›˜ Ì ÈÛÙÔÚÈÎfi Ê˘Ì·Ù›ˆÛ˘ ‹ ıÂÙÈ΋ Mantoux ÙÔ infliximab ÌÔÚ› Ó· ¯ÔÚËÁËı› ÌfiÓÔ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ·ÓÙ›Ê˘Ì·ÙÈ΋ ·ÁˆÁ‹.
™ÎÏËÚ›Ùȉ·
Ÿˆ˜ Û˘Ì‚·›ÓÂÈ Î·È Ì ÙȘ Ú·ÁÔÂȉ›Ùȉ˜, ¤ÙÛÈ Î·È Ì ÙȘ ÛÎÏËÚ›Ùȉ˜ ÙÔ etanercept ·ÚÔ˘ÛÈ¿˙ÂÈ ÌÂȈ̤ÓË ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÛÙËÓ
ÔÊı·ÏÌÈ΋ ÊÏÂÁÌÔÓ‹ ·ÎfiÌ· Î·È ·Ó ¤¯ÂÈ ıÂÙÈο ·ÔÙÂϤÛÌ·Ù· ÁÈ·
ÙË Û˘ÛÙËÌ·ÙÈ΋ ¿ıËÛË, ·ÓÙ›ıÂÙ· ÙÔ infliximab ‰Ú· ¢ÂÚÁÂÙÈο ÛÂ
ÛÎÏËÚ›Ùȉ· Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ƒÂ˘Ì·ÙÔÂȉ‹ ∞ÚıÚ›Ùȉ·, Ì ÓfiÛÔ
Wegener, Ì ¡Â·ÓÈ΋ π‰ÈÔ·ı‹ ∞ÚıÚ›Ùȉ·, ηıÒ˜ Î·È ÌÂ Û˘ÛÙËÌ·ÙÈ΋ ·ÁÁÂÈ›Ùȉ·.
∆Ô ˘„ËÏfi ÎfiÛÙÔ˜ Ù˘ ıÂÚ·›·˜ (ÂÚ› Ù· 1.000 ¢ÚÒ ÙÔ Ì‹Ó·) ·ÔÙÂÏ› ¤Ó· ·ÎfiÌ· ·Ú¿ÁÔÓÙ· Ô˘ ÔÊ›ÏÔ˘Ì ӷ Ï¿‚Ô˘Ì ÛÔ‚·Ú¿
˘’ fi„Ë Ì·˜ ÚÈÓ ·ÔÊ·Û›ÛÔ˘Ì ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛË.
∫˘ÛÙÂÔÂȉ¤˜ Ô›‰ËÌ· Ù˘ ˆ¯Ú¿˜ ÛÙȘ Ú·ÁÔÂȉ›Ùȉ˜
™˘ÌÂÚ¿ÛÌ·Ù·
∆Ô ¯ÚfiÓÈÔ, ·ÓıÂÎÙÈÎfi ΢ÛÙÂÔÂȉ¤˜ Ô›‰ËÌ· Ù˘ ˆ¯Ú¿˜, Ô˘ ·ÔÙÂÏ›
ÙËÓ Û˘¯ÓfiÙÂÚË ·ÈÙ›· ÛÔ‚·Ú‹˜ Ì›ˆÛ˘ Ù˘ ÔÙÈ΋˜ Ô͇ÙËÙ·˜ ÛÙȘ
¯ÚfiÓȘ Ú·ÁÔÂȉ›Ùȉ˜, ÌÔÚ› Ó· ‚ÂÏÙȈı› ·Ó·ÙÔÌÈο Î·È ÛÙÔ 60%
Ó· ˘ÔÛÙÚ¤„ÂÈ Ï‹Úˆ˜ ÌÂÙ¿ ·fi ÙËÓ ¯ÔÚ‹ÁËÛË 2 ‹ 3 ‰fiÛˆÓ
infliximab. ªÂ ‚¿ÛË ÙËÓ ÂÌÂÈÚ›· Ì·˜ Ë ‚ÂÏÙ›ˆÛË Ù˘ ÔÙÈ΋˜ Ô͇ÙËÙ·˜ ÂÌÊ·Ó›˙ÂÙ·È ·ÚÁfiÙÂÚ· ·ÏÏ¿ ‰È·ÚΛ ÂÚÈÛÛfiÙÂÚÔ ÛÂ
Û‡ÁÎÚÈÛË Ì ÙËÓ ÂÓ‰Ô¸·ÏÔÂȉÈ΋ ¤Á¯˘ÛË ÙÚÈ·ÌÎÈÓÔÏfiÓ˘.
∞Ó Î·È ·Ô˘ÛÈ¿˙Ô˘Ó ÔÈ ÌÂÁ¿Ï˜, Ù˘¯·ÈÔÔÈË̤Ó˜, ÂÏÂÁ¯fiÌÂÓ˜,
ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Ë ‰˘Ó·ÌÈ΋ ÙˆÓ ·ÓÙ›-TNF ·Ú·ÁfiÓÙˆÓ ÛÙË ıÂÚ·›· ÙˆÓ ÛÔ‚·ÚÒÓ ÔÊı·ÏÌÈÎÒÓ ÊÏÂÁÌÔÓÒÓ Â›Ó·È ÚÔÊ·Ó‹˜ ηÈ
ÔÊ›ÏÔ˘Ì ӷ ‰ÈÂÚ¢ӋÛÔ˘Ì ÂÚ·ÈÙ¤Úˆ ÙȘ ÂӉ›ÍÂȘ ÙÔ˘˜.
1. ∆· ÌÔÓÔÎψÓÈο ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ TNF (infliximab,
adalimumab) ¤¯Ô˘Ó ·ԉ‰ÂÈÁ̤ÓË ‰Ú¿ÛË Û ·ÓÙ›ıÂÛË ÌÂ
ÙÔÓ ‰È·Ï˘Ùfi ˘Ô‰Ô¯¤· TNF (etanercept) Ô˘ Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Â›Ó·È ·ÌÊ›‚ÔÏË.
ÕÏϘ ÔÊı·ÏÌÈΤ˜ ·ı‹ÛÂȘ
OÈ ·ÓÙ›- TNF ·Ú¿ÁÔÓÙ˜ ¤¯Ô˘Ó ¯ÚËÛÈÌÔÔÈËı› ¢ηÈÚȷο Ì ˘ÔÛ¯fiÌÂÓ· ·ÔÙÂϤÛÌ·Ù· Û ¿ÏϘ ÔÊı·ÏÌÈΤ˜ ·ı‹ÛÂȘ, fiˆ˜ ÛÂ
ÔÊı·ÏÌÔ¿ıÂÈ· Graves (etanercept) Î·È Û ȉÈÔ·ı‹ Ì˘ÔÛ›Ùȉ·
ÎfiÁ¯Ô˘ (infliximab). ∂Ì›˜ ‰ÔÎÈÌ¿Û·Ì ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘
infliximab Û ‰È·‚ËÙÈÎfi ΢ÛÙÂÔÂȉ¤˜ Ô›‰ËÌ· ˆ¯Ú¿˜ Î·È Û ˘ÁÚ‹˜
ÌÔÚÊ‹˜ ÂÎʇÏÈÛË Ù˘ ˆ¯Ú¿˜ Û¯ÂÙÈ˙fiÌÂÓË Ì ÙËÓ ËÏÈΛ· Î·È ‹‰Ë
¤¯Ô˘Ì ÍÂÎÈÓ‹ÛÂÈ ÚÔÔÙÈΤ˜, Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂȂ‚·ÈÒÛÔ˘Ì ٷ Úfi‰ÚÔÌ· ·ÔÙÂϤÛÌ·Ù· Ì·˜.
2. ∏ ¯ÔÚ‹ÁËÛË 3 ‰fiÛÂˆÓ infliximab ÌÔÚ› Ó· Á›ÓÂÙ·È Û ÔÍ›˜ Ô›ÛıȘ Ú·ÁÔÂȉ›Ùȉ˜ Ì fiÚ·ÛË Î¿Ùˆ ÙˆÓ 2/10 ‹ fiÙ·Ó
Û˘Ó˘¿Ú¯ÂÈ ÂÎÙÂٷ̤ÓË ·ÁÁÂÈ›Ùȉ· Ô˘ ·ÂÈÏ› ÙËÓ fiÚ·ÛË.
∏ ÓfiÛÔ˜ ∞‰·Ì·ÓÙÈ¿‰Ë-Behçet ·ÔÙÂÏ› Û·Ê‹ ¤Ó‰ÂÈÍË ¯ÔÚ‹ÁËÛ˘, ÂÓÒ Ë Û·ÚÎÔ›‰ˆÛË, Ë È‰ÈÔ·ı‹˜ Ô›ÛıÈ· Ú·ÁÔÂȉ›Ùȉ· Î·È ÙÔ ¯ÚfiÓÈÔ, ·ÓıÂÎÙÈÎfi ΢ÛÙÂÔÂȉ¤˜ Ô›‰ËÌ· ˆ¯Ú¿˜
·ÔÙÂÏÔ‡Ó Û¯ÂÙÈΤ˜ ÂӉ›ÍÂȘ.
3. ∏ Ì·ÎÚÔ¯ÚfiÓÈ· ¯ÔÚ‹ÁËÛË infliximab ÌÔÚ› Ó· Á›ÓÂÙ·È ÛÂ
ÂÚÈÙÒÛÂȘ ÌË ÏÔÈÌÒ‰Ô˘˜ Ú·ÁÔÂȉ›Ùȉ·˜, Ô˘ ‰ÂÓ ·ÓÙ·ÔÎÚ›ÓÔÓÙ·È ÛÙËÓ Î·ıÈÂڈ̤ÓË ıÂÚ·›· ÌÂ Û˘Ó‰˘·ÛÌfi ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ Î·È ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ. ∏ ÓfiÛÔ˜ ∞‰·Ì·ÓÙÈ¿‰Ë-Behçet, Ë ¡Â·ÓÈ΋ π‰ÈÔ·ı‹˜ ∞ÚıÚ›Ùȉ·, ÔÈ ÔÚÔ·ÚÓËÙÈΤ˜ ÛÔÓ‰˘Ï·ÚıÚÔ¿ıÂȘ Î·È Ù· ÊÏÂÁÌÔÓÒ‰Ë ÓÔÛ‹Ì·Ù·
ÙÔ˘ ÂÓÙ¤ÚÔ˘ ·ÔÙÂÏÔ‡Ó Û·Ê›˜ ÂӉ›ÍÂȘ ÁÈ· ¯ÔÚ‹ÁËÛË. ∆Ô
adalimumab ÌÔÚ› Ó· ¯ÔÚËÁËı› ÂÓ·ÏÏ·ÎÙÈο.
∞ÓÂÈı‡ÌËÙ˜ ‰Ú¿ÛÂȘ
OÈ ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ∆¡F-· Û¯ÂÙ›˙ÔÓÙ·È Ì ÛÔ‚·Ú¤˜, ·ÏÏ¿ Â˘Ù˘¯Ò˜
Û¿ÓȘ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ, ÙfiÛÔ Û ÙÔÈÎfi fiÛÔ Î·È Û˘ÛÙËÌ·ÙÈÎfi Â›‰Ô. ø˜ ÔÊı·ÏÌÈΤ˜ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ¤¯Ô˘Ó
·Ó·ÊÂÚı› ·ÌÊÔÙÂÚfiÏ¢ÚË ÚfiÛıÈ· ÈÛ¯·ÈÌÈ΋ ÔÙÈÎÔ¿ıÂÈ·, ÔÈÛıÔ‚ÔÏ‚È΋ ÔÙÈ΋ Ó¢ڛÙȉ· Î·È ÏÔÈÌÒÍÂȘ (ÌÔÏ˘ÛÌ·ÙÈ΋ Ù¤ÚÌÈÓıÔ,
ÂÓ‰ÔÊı·ÏÌ›Ùȉ· ·fi Ê˘Ì·Ù›ˆÛË, pr. acnes Î·È Mycobacterium
chelonae). ™Â Û˘ÛÙËÌ·ÙÈÎfi Â›Â‰Ô Ë ıÂÚ·›· Ì ·ÓÙ›-∆NF ¤¯ÂÈ
Û˘Û¯ÂÙÈÛı› Ì ηÈÚÔÛÎÔÈΤ˜ ÏÔÈÌÒÍÂȘ (Ê˘Ì·Ù›ˆÛË, ÎÚ˘ÙfiÎÔÎÎÔ, Ó¢ÌÔ·ÛÙË, ·ÛÚÂÁ›ÏψÛË, ÏÈÛÙÂÚ›ˆÛË), ‰È·Ù·Ú·¯¤˜ ·›Ì·-
4. ∏ ÛÎÏ‹Ú˘ÓÛË Î·Ù¿ Ͽη˜, Ë Î·Ú‰È·Î‹ ·ÓÂ¿ÚÎÂÈ· Î·È Ë
ÚfiÛÊ·ÙË Û˘ÛÙËÌ·ÙÈ΋ Ïԛ̈ÍË ·ÔÙÂÏÔ‡Ó ·fiÏ˘Ù˜
·ÓÙÂӉ›ÍÂȘ ¯ÔÚ‹ÁËÛ˘. ∏ ıÚÔÌ‚ˆÙÈ΋ ‰È¿ıÂÛË Î·È Ë
170
E§§HNIKH Oº£A§MO§O°IKH ETAIPEIA
Necrosis Factor antagonists: Preliminary Evidence for an
Emerging Approach in the Treatment of Ocular Inflammation.
Retina. 2007;27(4):399-413. ***
Ê˘Ì·Ù›ˆÛË ·ÔÙÂÏÔ‡Ó Û¯ÂÙÈΤ˜ ·ÓÙÂӉ›ÍÂȘ.
5. ∏ Û˘Ó¯ÔÚ‹ÁËÛË ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ, ·Ó Î·È ‰ÂÓ ıˆÚ›ٷÈ
··Ú·›ÙËÙË, ÌÔÚ› Ó· ‚ÂÏÙÈÒÛÂÈ Ù· ·ÔÙÂϤÛÌ·Ù·
∫ÏÈÓÈΤ˜ ÌÂϤÙ˜
¶ÚÔÙÂÈÓfiÌÂÓË µÈ‚ÏÈÔÁÚ·Ê›· (Ô ·ÚÈıÌfi˜ ÙˆÓ ·ÛÙÂÚ›ÛÎˆÓ ‰Â›¯ÓÂÈ
ÙÔ ÂӉȷʤÚÔÓ)
1. Reiff A, Takei S, Sadeghi S, Stout A, Shaham B, Bernstein B,
Gallagher K, Stout T. Etanercept therapy in children with
treatment-resistant uveitis. Arthritis Rheum. 2001;44(6):14115. *
2. Smith JR, Levinson RD, Holland GN, Jabs DA, Robinson MR,
Whitcup SM, Rosenbaum JT. Differential efficacy of tumor
necrosis factor inhibition in the management of inflammatory
eye disease and associated rheumatic disease. Arthritis
Rheum. 2001;45(3):252-7. **
3. Sfikakis PP, Theodossiadis PG, Katsiari CG, Kaklamanis P,
Markomichelakis NN. Effect of infliximab on sight-threatening
panuveitis
in
Behcet's
disease.
Lancet.
2001;28;358(9278):295-6. ***
4. Estrach C, Mpofu S, Moots RJ. Behcet's syndrome: response
to infliximab after failure of etanercept. Rheumatology
(Oxford). 2002;41(10):1213-4. *
5. Sfikakis PP, Kaklamanis PH, Elezoglou A, Katsilambros N,
Theodossiadis PG, Papaefthimiou S, Markomichelakis N.
Infliximab for recurrent, sight-threatening ocular inflammation
in Adamantiades-Behcet disease. Ann Intern Med.
2004;140(5):404-6. ***
6. Ohno S, Nakamura S, Hori S, Shimakawa M, Kawashima H,
Mochizuki M, Sugita S, Ueno S, Yoshizaki K, Inaba G.
Efficacy, safety, and pharmacokinetics of multiple
administration of infliximab in Behcet's disease with refractory
uveoretinitis. J Rheumatol. 2004;31(7):1362-8. ***
7. Giansanti F, Barbera ML, Virgili G, Pieri B, Emmi L, Menchini U.
Infliximab for the treatment of posterior uveitis with retinal
neovascularization in Behcet disease. Eur J Ophthalmol.
2004;14(5):445-8.
8. Tugal-Tutkun I, Mudun A, Urgancioglu M, Kamali S, Kasapoglu
E, Inanc M, Gul A. Efficacy of infliximab in the treatment of
uveitis that is resistant to treatment with the combination of
azathioprine, cyclosporine, and corticosteroids in Behcet's
disease: an open-label trial. Arthritis Rheum. 2005;52(8):247884. ***
9. Abu El-Asrar AM, Abboud EB, Aldibhi H, Al-Arfaj A. Long-term
safety and efficacy of infliximab therapy in refractory uveitis
due to Behcet's disease. Int Ophthalmol. 2005;26(3):83-92. **
10. Melikoglu M, Fresko I, Mat C, Ozyazgan Y, Gogus F, Yurdakul
S, Hamuryudan V, Yazici H. Short-term trial of etanercept in
Behcet's disease: a double blind, placebo controlled study. J
Rheumatol. 2005;32(1):98-105. ***
11. Lanthier N, Parc C, Scavennec R, Dhote R, Brezin AP, Guillevi
L. Infliximab in the treatment of posterior uveitis in Behcet's
disease. Long term follow up in four patients. Presse Med.
2005;34(13):916-8.
12. Murray PI, Sivaraj RR. Anti-TNF-alpha therapy for uveitis:
Behcet and beyond. Eye. 2005;19(8):831-3 **
13. Mushtaq B, Saeed T, Situnayake RD, Murray PI. Adalimumab
for sight-threatening uveitis in Behcet's disease. Eye. 2006 7;*
14. Reiff A. Long-term outcome of etanercept therapy in children
with treatment-refractory uveitis. Arthritis Rheum.
2003;48(7):2079-80. **
15. Smith JA, Thompson DJ, Whitcup SM, Suhler E, Clarke G,
Smith S, Robinson M, Kim J, Barron KS. A randomized,
∞Ó·ÛÎÔ‹ÛÂȘ
1. Sfikakis PP. Behcet's disease: a new target for anti-tumour
necrosis factor treatment. Ann Rheum Dis. 2002;61 Suppl
2:ii51-3 ***
2. Rosenbaum JT, Smith JR. Anti-TNF therapy for eye
involvement in spondyloarthropathy. Clin Exp Rheumatol.
2002;20(6 Suppl 28):S143-5 **
3. Dick AD, Forrester JV, Liversidge J, Cope AP. The role of
tumour necrosis factor (TNF-alpha) in experimental
autoimmune uveoretinitis (EAU). Prog Retin Eye Res.
2004;23(6):617-37 *
4. Hyrich KL, Silman AJ, Watson KD, Symmons DPM. Anti tumor
necrosis factor a therapy in rheumatoid arthritis: an update on
safety. Ann Rheum Dis 2004;63:1538-1543 **
5. Braun J, Baraliakos X, Listing J, Sieper J. Decreased incidence
of anterior uveitis in patients with ankylosing spondylitis
treated with the anti-tumor necrosis factor agents infliximab
and etanercept. Arthritis Rheum. 2005;52(8):2447-51. *
6. de Smet MD. News on therapies for uveitis. J Fr Ophtalmol.
2005;28(5):556-61 **
7. Haraoui B. Differentiating the efficacy of the tumor necrosis
factor inhibitors. Semin Arthritis Rheum. 2005;34(5 Suppl1):711 **
8. Keystone EC. Safety of biological therapies. An update J
Rheumatol 2005;32(suppl74):8-12 ***
9. Nussenbatt R. Treating intraocular inflammatory disease in the
21st century. Arch Ophthalmol 2005;123:1000-1001 ***
10. Hale S, Lightman S. Anti-TNF therapies in the management of
acute and chronic uveitis. Cytokine. 2006 21;33(4):231-7 ***
11. Hommes DW, Oldenburg B, van Bodegraven AA, van
Hogezand RA, de Jong DJ, Romberg-Camps MJ, van der
Woude J, Dijkstra G; Dutch Initiative on Crohn and Colitis
(ICC). Guidelines for treatment with infliximab for Crohn's
disease. Neth J Med. 2006;64(7):219-29 *
12. Lightman S, McCluskey PJ. Which way forward for treatment
of severe ocular inflammation? Clin Experiment Ophthalmol.
2006;34(4):293-4. ***
13. Pipitone N, Olivieri I, Cantini F, Triolo G, Salvarani C. New
approaches in the treatment of Adamantiades-Behcet's
disease. Curr Opin Rheumatol. 2006;18(1):3-9 *
14. Read RW. Uveitis: advances in understanding of
pathogenesis and treatment. Curr Rheumatol Rep.
2006;8(4):260-6 ***
15. Taban M, Dupps WJ, Mandell B, Perez VL. Etanercept
(enbrel)-associated inflammatory eye disease: case report
and review of the literature. Ocul Immunol Inflamm.
2006;14(3):145-50. *
16. Sfikakis PP, Markomichelakis N, Alpsoy E, Assaad-Khalil S,
Bodaghi B, Gul A, Ohno S, Pipitone N, Schirmer M, Stanford
M, Wechsler B, Zouboulis C, Kaklamanis P, Yazici H. Anti-TNF
therapy in the management of Behcet's disease--review and
basis for recommendations. Rheumatology (Oxford). 2007
Apr 2 ***
17. Theodossiadis PG, Markomichelakis NN, Sfikakis PP. Tumor
171
40Ô ¶ANE§§HNIO Oº£A§MO§O°IKO ™YNE¢PIO
placebo-controlled, double-masked clinical trial of etanercept
for the treatment of uveitis associated with juvenile idiopathic
arthritis. Arthritis Rheum. 2005;53(1):18-23. ***
16. Richards JC, Tay-Kearney ML, Murray K, Manners P.
Infliximab for juvenile idiopathic arthritis-associated uveitis.
Clin Experiment Ophthalmol. 2005;33(5):461-8. *
17. Schmeling H, Horneff G. Etanercept and uveitis in patients
with juvenile idiopathic arthritis. Rheumatology (Oxford).
2005;44(8):1008-11.
18. Kahn P, Weiss M, Imundo LF, Levy DM. Favourable response
to high-dose infliximab for refractory childhood uveitis.
Ophthalmology. 2006;113(5):860-4.e2. ***
19. Foeldvari I, Nielsen S, Kummerle-Deschner J, Espada G,
Horneff G, Bica B, Olivieri AN, Rajaraman RT, Kimura Y, Li S,
Haines K, Chu DS. Retrospective case review of pediatric
patients with uveitis treated with infliximab. Ophthalmology.
2006;113(2):308-14 ***
20. Saurenmann RK, Levin AV, Feldman BM, Laxer RM,
Schneider R, Silverman ED. Risk of new-onset uveitis in
patients with juvenile idiopathic arthritis treated with antiTNFalpha agents. J Pediatr. 2006;149(6):833-6. *
21. Saurenmann RK, Levin AV, Rose JB, Parker S, Rabiitch T,
Tyrrell PN, Feldman BM, Laxer RM, Schneider R, Silverman
ED. Tumour necrosis factor alpha inhibitors in the treatment of
childhood uveitis. Rheumatology (Oxford). 2006;45(8):982-9.
**
22. Foeldvari I, Nielsen, S, Kummerle-Deschner J, Espada G,
Horneff G, Bic B, Olivieri AN, Wierk A, Saurenmann RK. Tumor
Necrosis Factor-alpha Blocker in Treatment of Juvenile
Idiopathic Arthritis-Associated Uveitis Refractory to Secondline Agents: Results of a Multinational. Survey .J Rheumatol.
2007 Mar 1 ***
23. Sharma SM, Ramanan AV, Riley P, Dick AD. Use of infliximab
in juvenile onset rheumatological disease associated
refractory uveitis: Efficacy in joint and ocular disease. Ann
Rheum Dis. 2006 Dec 14 ***
24. Vazquez-Cobian LB, Flynn T, Lehman TJ. Adalimumab
therapy for childhood uveitis. J Pediatr. 2006;149(4):572-5. **
25. Tynjala P, Lindahl P, Honkanen V, Lahdenne P, Kotaniemi K.
Infliximab and etanercept in the treatment of chronic uveitis
associated with refractory juvenile idiopathic arthritis. Ann
Rheum Dis.2007;66(4):548-50. *
26. Biester S, Deuter C, Michels H, Haefner R, KuemmerleDeschner J, Doycheva D, Zierhut M. Adalimumab in the
therapy of uveitis in childhood. Br J Ophthalmol.
2007;91(3):319-24. ***
27. El-Shabrawi Y, Hermann J. Anti-tumor necrosis factor-alpha
therapy with infliximab as an alternative to corticosteroids in
the treatment of human leukocyte antigen B27-associated
acute anterior uveitis. Ophthalmology. 2002;109(12):2342-6.
**
28. Guignard S, Gossec L, Salliot C, Ruyssen-Witrand A, Luc M,
Duclos M, Dougados M. Efficacy of tumor necrosis factor
blockers in reducing uveitis flares in patients with
spondylarthropathy: a retrospective study. Ann Rheum Dis.
2006;65(12):1631-4. **
29. Foster CS, Tufail F, Waheed NK, Chu D, Miserocchi E,
Baltatzis S, Vredeveld CM. Efficacy of etanercept in
preventing relapse of uveitis controlled by methotrexate. Arch
Ophthalmol. 2003;121(4):437-40. *
30. Murphy CC, Ayliffe WH, Booth A, Makanjuola D, Andrews PA,
Jayne D. Tumor necrosis factor-a blockade with infliximab for
refractory uveitis and scleritis. Ophthalmology 2004;111:352356 ***
31. Suhler EB, Smith JR,Wertheim MS, Lauer AK, Kurz DE,
Pickard TD, Rosenbaum JT. A prospective trial of infliximab
therapy for refractory uveitis : preliminary safety and efficacy
outcomes. Arch Ophthalmol, 2005;123(7)903-912 ***
32. Lindstedt EW, Baarsma GS, Kuijpers RW, van Hagen PM.
Anti-TNF-alpha therapy for sight threatening uveitis.Br J
Ophthalmol. 2005;89(5):533-6. **
33. Baughmann RR, Bradley DA, Lower EE. Infliximab in chronic
ocular inflammation. Int J Clin Pharmacol Ther 2005;43:7-11.
34. Galor A, Perez VL, Hammel JP, Lowder CY. Differential
effectiveness of etanercept and infliximab in the treatment of
ocular inflammation. Ophthalmology. 2006;113(12):2317-23.
***
35. Sari I, Akkoc N. Hypopyon uveitis. J Rheumatol.
2006;33(10):2097-8.*
36. Markomichelakis NN, Theodossiadis PG, Pantelia E,
Papaefthimiou S, Theodossiadis GP, Sfikakis PP. Infliximab
for chronic cystoid macular edema associated with uveitis.
Am J Ophthalmol. 2004;138(4):648-50. **
37. Markomichelakis NN, Theodossiadis PG, Sfikakis PP.
Regression of neovascular age-related macular degeneration
following infliximab therapy. Am J Ophthalmol 2005;139:537540 *
38. Garrity JA, Coleman AW, Matteson EL, Eggenberger ER,
Waitzman DM. Treatment of recalcitrant idiopathic orbital
inflammation (chronic orbital myositis) with infliximab Am J
Ophthalmol 2004;138:925-930. *
39. Paridaens D, van den Bosch WA, van der Loos TL, Krenning
EP, van Hagen PM. The effect of etanercept on Graves’
ophthalmopathy: a pilot study. Eye 2006;20:154-162.*
40. Adan A, Santi R, Bures A, Casaroli-ano RP. Successful
treatment with infliximab in a patient with Diffuse Subretinal
Fibrosis syndrome. Am J Ophthalmol. 2007;143(3):533-4.*
41. Jolly M, Curran JJ. Infliximab-responsive uveitis and vasculitis
in a patient with Takayasu arteritis. J Clin Rheumatol.
2005;11(4):213-5. *
42. Sfikakis PP, Markomichelakis N, Theodossiadis GP,
Grigoropoulos V, Katsilambros N, Theodossiadis PG.
Regression of sight-threatening macular edema in type 2
diabetes following treatment with the anti-tumor necrosis
factor monoclonal antibody infliximab. Diabetes Care.
2005;28(2):445-7. *
43. Brown SL, Greene MH, Gershon SK, Edwards ET, Braun MM.
Tumor necrosis factor antagonist therapy and lymphoma
development: twenty-six cases reported to the Food and Drug
Administration. Arthritis Rheum 2002;46:3151-3158. *
44. De Rosa FG, Shaz D, Campagna AC, Dellaripa PE, Khettry U,
Craven DE. Invasive pulmonary aspergillosis soon after
therapy with infliximab, a tumour necrosis factor-alphaneutralizing antibody. A possible healthcare associated case?
Infect Control Hosp Epidemiol 2003;24:477-482.
45. Fonollosa A, Segura A, Giralt J, Garcia-Arumi J. Tuberculous
uveitis after treatment with etanercept. Graefes Arch Clin Exp
Ophthalmol. 2007 16;
46. Gardam MA, Keystone EC, Menzies R, Manners S, Skamene
E, Long R, Vinh DC. Anti-tumour necrosis factor agents and
tubercolosis risk: mechanisms of action and clinical
management. Lancet Infect Dis, 2003;3(3): 148-155.
47. Haerter G.et al. Cytomegalovirus retinitis in a patient treated
with anti-tumor necrosis factor alpha antibody therapy for
172
E§§HNIKH Oº£A§MO§O°IKH ETAIPEIA
∂ÚÁ·ÛÙËÚȷΤ˜ ÌÂϤÙ˜
rheumatoid arthritis. Clin Infect Dis, 2004;39(9):88-94
48. Lee JH, Slifman NR, Gershon SK, Edwards ET, Schwieterman
WD, Siegel N, Wise RP, Brown SL, Udall JN Jr, Braun MM.
Life-threatening histoplasmosis complicating immunotherapy
with tumor necrosis factor alpha antagonists infliximab and
etanercept Arthritis Rheum. 2002;46:2565-70
49. Montero JA, Ruiz-Moreno JM, Rodriguez AE, Ferrer C,
Sanchis E, Alio JL. Endogenous endophthalmitis by
Propionibacterium acnes associated with leflunomide and
adalimumab therapy. Eur J Ophthalmol. 2006;16(2):343-5.
50. Slifman NR, Gershon SK, Lee JH, Edwards ET, Braun MM.
Listeria monocytogenes infection as a complication of
treatment with tumor necrosis factor alpha-neutralizing
agents. Arthritis Rheum 2003;48:319-324
51. Stewart MW, Alvarez S, Ginsburg WW, Shetty R, McLain WC,
Sleater JP. Visual recovery following Mycobacterium
chelonae endophthalmitis. Ocul Immunol Inflamm.
2006;14(3):181-3.
52. Tai TL, O'Rourke KP, McWeeney M, Burke CM, Sheehan K,
Barry M. Pneumonocystis carinii pneumonia following a
second infusion of infliximab. Rheumatology (Oxford)
2002;41:951-952
53. ten Tusscher MP, Jacobs PJ, Busch MJ, de Graaf L, Diemont
WL Bilateral anterior toxic optic neuropathy and the use of
infliximab. BMJ. 2003;326:579
54. van Oosten BW, et al. Increased MRI activity and immune
activation in two multiple sclerosis patients with the
monoclonal anti-tumour necrosis factor antibody cA2.
Neurology, 1996;47(6):1531-1534 *
55. Wegscheider BJ, El-Shabrawi L, Weger M, Ardjomand N,
Hermann J, Aberer E, El-Shabrawi Y. Adverse skin reactions
to infliximab in the treatment of intraocular inflammation. Eye.
2007;21(4):547-9.
1. Rosenbaum JT, Hoves EL, Rubin RM, Samples JR. Ocular
inflammatory effects of intravitreally injected tumor necrosis
factor. Am J Pathol 1988;133:47-53
2. Fleisher LN, Ferell JB, Mc Gahan MC. Ocular inflammatory
effects of intravitreally injected tumor necrosis factor and
endotoxin. Inflammation 1990; 14: 325-335
3. Sartani G, Silver PB, Rizzo LV, Chan CC, Wiggert B,
Mastorakos G, Caspi RR. Anti-tumor necrosis factor alpha
therapy suppresses the induction of experimental
autoimmune uveoretinitis in mice by inhibiting antigen
priming. Invest Ophthalmol Vis Sci. 1996; 37(11):2211-8.
4. Chronopoulou H, Tzavara N, Ekonomopoulos N, Zafirakis P,
Theodosiadis P, Tzioufas T, Markomichelakis N. High levels of
TNF-a in the aqueous humor in patients suffering from
Adamantiades- µehçet’s disease: preliminary results. Invest
Ophthalmol Vis Sci 2001;42S:708
5. Elezoglou A, Sfikakis PP, Vaiopoulos G, et al. Serum levels of
soluble TNF receptor-II (p 75), circulating T-cells, and
Adamantiades- µehçet disease activity. Adv Clin Exp Biol
2003; 528:261-265
6. Sfikakis PP, Kollias G. TNF biology in experimental and clinical
arthritis. Curr Opin Rheumatol 2003;15:380-386
7. Strunk J, Bundke E, Lange U. Anti-TNF-alpha antibody
infliximab and glucocorticoids reduce serum vascular
endothelial growth factor levels in patients with rheumatoid
arthritis. Rheumatol Int 2006;26:252-256
∞. ¡fiÛÔ˜ ∞‰·Ì·ÓÙÈ¿‰Ë-Behçet. ¶·ÓÚ·ÁÔÂȉ›ÈÙȉ· Ì ˘fi˘ÔÓ. µ. ªÈ· Ë̤ڷ ÌÂÙ¿ ÙËÓ ÂÓ‰ÔÊϤ‚È· ¤ÓÂÛË infliximab.
∞. ¡fiÛÔ˜ ∞‰·Ì·ÓÙÈ¿‰Ë-Behçet. ¶·ÓÚ·ÁÔÂȉ›ÈÙȉ· Ì ˘·Ï›Ùȉ· 4+. µ. ªÈ· ‚‰ÔÌ¿‰· ÌÂÙ¿ ÙËÓ ÂÓ‰ÔÊϤ‚È· ¤ÓÂÛË infliximab.
173
40Ô ¶ANE§§HNIO Oº£A§MO§O°IKO ™YNE¢PIO
∞. ¡fiÛÔ˜ ∞‰·Ì·ÓÙÈ¿‰Ë-Behçet. ∞ÌÊÈ‚ÏËÛÙÚÔÂȉ›Ùȉ· µ. ªÈ· ‚‰ÔÌ¿‰· ÌÂÙ¿ ÙËÓ ÂÓ‰ÔÊϤ‚È· ¤ÓÂÛË infliximab. °. ¢‡Ô ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ .
∞. ¡fiÛÔ˜ ∞‰·Ì·ÓÙÈ¿‰Ë-Behçet. ∞ÁÁÂÈ›Ùȉ· µ. ¢‡Ô ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ÂÓ‰ÔÊϤ‚È· ¤ÓÂÛË infliximab.
∞. ¡fiÛÔ˜ ∞‰·Ì·ÓÙÈ¿‰Ë-Behçet. ∫˘ÛÙÂÔÂȉ¤˜ Ô›‰ËÌ· ˆ¯Ú¿˜ µ. ¢‡Ô ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ·fi ÂÓ‰ÔÊϤ‚È· ¤ÓÂÛË infliximab.
∞. ™ÎÏËÚ›Ùȉ· ·ÓıÂÎÙÈ΋ ÛÙË ıÂÚ·›· µ. ¢‡Ô Ë̤Ú˜ ÌÂÙ¿ ÂÓ‰ÔÊϤ‚È· ¤ÓÂÛË infliximab. °. ªÈ· ‚‰ÔÌ¿‰· ÌÂÙ¿. ¢. ¢˘Ô ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿
174
E§§HNIKH Oº£A§MO§O°IKH ETAIPEIA
∞. π‰ÈÔ·ı‹˜ Ô›ÛıÈ· Ú·ÁÔÂȉ›Ùȉ· ·ÓıÂÎÙÈ΋ ÛÙËÓ ıÂÚ·›· Ì ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹, ΢ÎÏÔÛÔÚ›ÓË Î·È ·˙·ıÈÔÚ›ÓË. µ. ªÈ· Ë̤ڷ ÌÂÙ¿ ÙËÓ
ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË infliximab. °. ªÂÙ¿ 4 Ë̤Ú˜. ¢. ªÂÙ¿ 7 Ë̤Ú˜. ∂. ªÂÙ¿ 10 Ë̤Ú˜. ∑. ªÂÙ¿ 14 Ë̤Ú˜.
∏. ªÂÙ¿ ·fi 6 Ì‹Ó˜, ÂÓÒ Ë ıÂÚ·›· Ì infliximab Û˘Ó¯›˙ÂÙ·È.
∞. ¢È·‚ËÙÈÎfi ΢ÛÙÔÂȉ¤˜ Ô›‰ËÌ· ˆ¯Ú¿˜. µ. ŒÓ· Ì‹Ó· ÌÂÙ¿ ÙËÓ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË infliximab
A. ∂Ï¿¯ÈÛÙ· ÎÏ·ÛÛÈ΋ ˘·ÌÊÈ‚ÏËÛÙÚÔÂȉÈ΋ ÓÂÔ·ÁÁ›ˆÛË Û ·ÛıÂÓ‹ Ì ËÏÈÎȷ΋ ÂÎʇÏÈÛË ˆ¯Ú¿˜.
µ. ŒÍË Ì‹Ó˜ ÌÂÙ¿ ıÂÚ·›· Ì infliximab.
175