<<

. 2
( 2 .)







1 49 1–2% 15–31% 33–67%
8–19%
4 43 9–21% 18–41% 8–19%
4–13%
6 31 8–26% 13–42% 6–19%
8–35%
12 23 2–9% 12–52% 1–4%
7–54%
18 13 1–8% 5–38% –
8–67%
36 12 3–25% 1–8,3% –
DAS 4

1 44 4–9% 8–18% 32–73%
8–22%
4 37 10–27% 10–27% 9–24%
8–28%
6 29 5–17% 12–41% 4–14%
7–30%
12 23 8–35% 6–26% 2–9%
7–54%
18 13 3–23% 3–23% –
8–67%
36 12 4–33% – –

Oaaeeoa 4. Au?a?aiiinou oiaiuoaiey ia?aiao?ia nonoaaiiai neia?iia o 50 aieuiuo
(any a?oiia, aac auaaeaiey ii?eeuo aieuiuo) e o 33 aieuiuo noa?oa 50 eao
()

>50 >50 >50
1 ian. ia 37% ia 27% ia 15% ia 19,6% ia 30% ia 25%
4 ian. ia 81% ia 61% ia 60% ia 53% ia 60% ia 64%
6 ian. ia 79% ia 59% ia 67% ia 62% ia 71% ia 72%
12 ian. ia 85% ia 63% ia 70% ia 69% ia 67% ia 59%



521

13, 8, 2005
eOCaAieaeEau
cee (1–2 ca 12 ianyoaa), a a inoaeuiuo neo?ayo iiaua oa, ii auei e o 5 aieuiuo noa?oa 50 eao. I?e oiaiuoa-
y?icee a iaeeeo nonoaaao ia aicieeaee (?en. 4) iee aicu eee ia?a?uaa a ea?aiee ai 3–4 iaaaeu auia-
Neaaoao ioiaoeou oi?ioo? ia?aiineiinou A?aau aaiea aiein i?ae?auaeinu e i?e aiciaiiaeaiee ea?a-
eae a ?aiiea, oae e a iicaiea n?iee aa i?eiaiaiey. iey aieaa ia ?aoeaeae?iaaei.
Aieuoeinoai ia?aeaoaeuiue ?aaeoee ?acaeaa?ony a Naycaiiue n i?eaiii i?aia?aoa a?eiiiiiaiaiue
ia?aua ianyou ea?aiey. E a a?oiia aieuiuo ii?eeiai neia?ii (flu–neia?ii), i?iyaey?ueeny ia?eiaaie ia-
aic?anoa i?eiaiaiea eaoeoiiieaa iieacaei oaiaea- aiiiaaiey, iciiaii, noaoaa?eeeoaoii, ieaeaeyie e
oai?eoaeuio? ia?aiineiinou i?aia?aoa, oioy e ia- oneeaieai aieae a nonoaaao, ?acaeaaeny oieuei o ii?e-
neieuei oo?a, ?ai a a?oiia aieuiuo iaiaa 50 eao euo aieuiuo (a 3–o neo?ayo) e i?ioiaee iinea e?aoei-
(oaae. 7). ?acaeoea ?acee?iuo iaoy?aeuo iiai?iuo ?a- a?aiaiiiai ia?a?uaa a ea?aiee.
aeoee, eioi?ua ia anaaaa auee naycaiu n i?eaiii A?a- Ca 36 ianyoaa ea?aiey A?aaie ca?aaeno?e?iaaii 37
au, ioia?aeinu o 89% aieuiuo (29 aieuiuo). Eiaiii o neo?aaa I?AE o 11 aieuiuo, ia iineaoae caoy?iiai oa-
ii?eeuo aieuiuo (oaae. 7) ?aua ?acaeaaeenu oa?aeoa?- ?aeoa?a e ia ioee?aaoaeny io ?anie?aoi?iuo caaieaaa-
iua aey A?aau neiioiiu iaia?aiineiinoe. Iaeaieaa iee a aiaiiaca. O 3 aieuiuo ioia?aeenu i?eciaee ino-
?anouie e ii?aaaeaiii naycaiiuie n i?iaiaeiie oa?a- ?ie iiaaiiiee; o 1 aieuiie aaa?au iaino?yeny o?iie-
ieae yaeyeenu aeea?ae?aneea i?iyaeaiey ei?iie eiea- ?aneee ieaeiiao?eo. Ai anao neo?ayo iiyaeaiey nei-
eecaoee (coa, ?a?a n nuiu?) o 67% aieuiuo, a oae?a ia- ioiiia eioaeoee ea?aiea A?aaie i?a?uaaeinu, i?iai-
?ooaiey ooieoee ?EO (aea?ay, iaoai?eci, oioiioa) o aeeanu aioeaaeoa?eaeuiay oa?aiey. Iinea eoie?iaaiey
16 aieuiuo (48%). Eiaiii o ii?eeuo aieuiuo iu auee eioaeoeiiiiai caaieaaaiey i?eai eaoeoiiieaa ai-
auio?aaiu ioiaieou A?aao a 6 neo?ayo ec–ca noieeiai ciaiiaeyeny. ?anoioa eioaeoeiiiuo caaieaaaiee ia
ei?iiai coaa e a 1 neo?aa ec–ca ?aoeaeae?o?uae aea- oiia A?aau ia caaenaea io aic?anoa aieuiuo.
?ae n?aaiae eioaineaiinoe, ianiio?y ia a?aiaiiua ia- ?acaeoea eioaeoeiiiuo caaieaaaiee, o?aiceoi?iia
?a?uau a ea?aiee, oiaiuoaiea aicu ai 10 ia/noo. e ia- iiauoaiea o?iaiy oa?iaioia ia?aie, e?aoeia?aiaiiia
cia?aiea ea?aiey neiioiiia iaia?aiineiinoe. O eeo ianoaaeeuiia oa?aiea AA naeaaoaeunoao?o eeou i aic-
ieaaoa 50 eao yoe ia?aeaoaeuiua neiioiiu auee ia- ii?iie eee iaioaiaiiie eo nayce n i?eaiii i?aia?aoa
iaa noieeeie e iinoaiaiii i?ioiaeee aac ieii?aoaeu- (n o?aoii aeeoaeuiiai i?eaia IIAI, iaee?ey niioono-
iie ioiaiu A?aau. O iieiaeiu aieuiuo, eioi?ui A?a- ao?ueo caaieaaaiee e niioonoao?uae oa?aiee). Ia io-
au auea ioiaiaia ec–ca coaa, a aiaiiaca auee aeea?- ia?aeinu oy?aeiai oa?aiey eioaeoeiiiuo caaieaaaiee,
ae?aneea ?aaeoee ia a?oaea aaceniua i?aia?aou, ?oi au?a?aiiiai ia?ooaiey ooieoee ia?aie, noieeiai ii-
aie?ii neo?eou i?eaioe?ii aey a?a?a aey aieaa aie- auoaiey AA, ?acenoaioiiai e aeiioaiceaiie oa?aiee. Ca
iaoaeuiiai ioiioaiey e oaeei aieuiui. O 4 ii?eeuo ia?eia iaae?aaiey ia auei caoeene?iaaii ie iaiiai
aieuiuo ioia?aeinu oaaee?aiea eiioaio?aoee nuai?i- neo?ay ?acaeoey na?uaciuo iiai?iuo i?iyaeaiee.
oi?iuo o?ainaieiac, uaei?iie oinoaoacu, ?–aeooa- A eeoa?aoo?a iienuaaaony, ?oi ia oiia A?aau i?e-
ia?ii o 7–8% aieuiuo iiyaeyaony a?oa?eaeuiay aeia?-
ieeo?ainiaioeaacu aieaa ?ai a 1,5 ?aca, iaiaei ie a
iaiii neo?aa yoi ia iineo?eei i?e?eiie i?ae?auaiey
Oaaeeoa 7. ?anoioa ?acaeoey neiioiiia
ea?aiey e i?ioiaeei naiinoiyoaeuii. Iiauoaiiia au-
iaia?aiineiinoe A?aau a caaeneiinoe
iaaaiea aiein ?aua ioia?aeinu o eeo iieiaiai aic?an-
io aic?anoa aieuiuo (% io ?enea aieuiuo)
Oaaeeoa 5. Aeiaieea iieacaoaeae nonoaaiiai
neia?iia a a?oiia ii?eeuo aieuiuo ?A
() > 50 < 50
±? ±? ±? Aea?ay 36% (1 ioiaia) 23,5%
±? ±? ±? Iaoai?eci 9% 23,5%
Ai ea?aiey 15,33±7,47 16,56± 7,02 60,96±2,26 Ei?iue coa e nuiu 67% (6 ioiai) 35%
1 ianyo 11,07±6,15** 13,31±6,18** 45,93±26,3** Iiauoaiiia
(i=32) 4,25±5,72** 3,25±5,1** 15,03±25,94 auiaaaiea aiein 15% 41%
4 ianyoa 4,90±5,01** 7,57±7,34** 21,0±16,72** Iiauoaiea o?iaiy
(i=26) 9,4±8,50** 8,73±6,79** 39,03±27,95 o?ainaieiac (> 1,5 ii?iu) 12% 6%
6 ianyoaa 6,50±7,37** 7,35± 8,34** 18,6±23,56** Iiauoaiea AA 9% 12%
(i=17) 9,00±8,61** 10,23±8,04** 44,17±32 Flu–neia?ii
12 ianyoaa 3,55±4,21* 5,0±3,55** 21,5±13,55* (a?eiiiiiaiaiue neia?ii) 9% 0
(i=10) 9,66±8,91** 11,5±5,12** 36,2±28,36 I?AE 57% 65%
Iiaaiiiey 6% 14%
I?eia?aiea: * p< 0,01 ** p< 0,001

Oaaeeoa 6. Yooaeoeaiinou ea?aiey ii?eeuo aieuiuo ?A eaoeoiiieaii ii e?eoa?eyi EULAR

DAS4 DAS28
. n/% . n/% . n/% , n/% . n/% n/%
1 n=27 18 – 67% 8 – 30% 1 – 3% n=32 20 – 62,5% 12 – 37,5% –
4 n=21 6 – 29% 6 – 29% 9 – 42% n=26 6 – 23% 8 – 31% 12 – 46%
6 n=16 2 – 13% 9 – 56% 5 – 31% n=17 5 – 29% 8 – 47% 4 – 24%
12 n=8 2 – 25% 1 – 12,5% 5 – 62,5% n=11 3 – 27% 3 – 27% 5 – 46%



522 13, 8, 2005
eOCaAieaeEau
9. Manna SK, Aggarwal BB. Immunosuppressive leflunomide metabolite (A77 1726)
blocks TNF–dependent nuclear factor–kb activation and gene expression. J Immunol.,
1999,162,2095–2102.
10. Hamilton L., Voinovic I., Bakhle Y., et al. The anti–inflammatory drug leflunomide
inhibits in vitro and in vivo the activity of COX–2 more potently than the induction of
COX–1 or iNOS. Br.J.Rheumatol., 1997,120,49
11. Kraan M.C., Reece R.G., Barg F.C., et al. Expression of ICAM–1 and MMP–12 in
rheumatoid synovial tissue after treatment with leflunomide or methotrexate. 63
Ann.Scient. Meet. Amer.Coll.Rheumatol., 1999,Boston.
12. Cao W, Kao P, Aoki Y., et al. A novel mechanism of action of the immunomodulato-
ry drug, leflunomide: augmentation of the immunosuppressive cytokine, TGF–bl, and
suppression of the immunostimulatory cytokine, IL–2. Transplaht. Proc.,
1996,28,3079–3080.
13. Zelinski T, Muller HJ, Scheyerbach R, et al. differential effects of leflunomide on
leucocytes: inhibition of rat in vivo adhesion and human in vitro oxidative burst with-
Oi?ioee yooaeo Oaiaeaoai?eoaeuiue yooaeo
out affecting surface marker modulation. Agents Actions 1994 Aug; 41 Spec.
?en. 4. N?aaiaa oaaee?aiea ?enea nonoaaiuo y?icee Iss.:276–8.
a caaeneiinoe io yooaeoa oa?aiee ii e?eoa?eyi EULAR 14. Lang R, Wagner H, Heeg K. Differential effects of the immunosuppressive agents
cyclosporine and leflunomide in vivo: Leflunomide blocks clonal T cell expansion yet
allows production of lymphokines and manifestation of T–cell–mediated shock.
oaicey eee ooy?aeyaony aa oa?aiea [32], iaiaei a iaoae
Transplantation 1995 Feb 15;59:382–9.
a?oiia aieuiuo aia caaeneiinoe io aic?anoa yoio oaii-
15. Prakash A, Jarvis B. Leflunomide: a review of its Use in Active rheumatoid Arthritis.
iai ia ioia?aeny, oioy 13 aieuiuo, iieo?aaoeo A?aao, Drugs 1999;58:1137–64.
no?aaaee a?oa?eaeuiie aeia?oaiceae e iieo?aee aioe- 16. Hamilton L., Voinovic I., Bakhle Y., et al. The anti–inflammatory drug leflunomide
aeia?oaiceiao? oa?aie?. Iienaii i?e i?eiaiaiee ingibits in vitro and in vivo the activity of COX–2 more potently than the induction of
COX–1 or iNOS. Br.J.Rheumatol., 1997,120,49
A?aau a ii?eeii aic?anoa ?acaeoea iae?iiaoee: ?aua –
17. Amitabh Prakash and Blair Jarvis. Leflunomide – a review of its use in active RA.
naini?iay iae?iiaoey e ?a?a – naini–iioi?iay iae?i-
Drugs 1999; 58:1137–1164.
iaoey [33,34]. Aic?ano aieuiuo eieaaaeny io 57 ai 78 18. N.C.eA?AUI?I, O.a.cOOIO‚. cO‚?A IO?‚IAIE? IA?AIE? eA: IA?IEAI? AEOU-
eao, n?aaiyy aeeoaeuiinou ea?aiey e iiiaioo ia?auo ‚E? E IIEIE?AOI? ?UUAIUE‚IOOU? IAUIUIOIE. cU?IO–O?IUE?AOI? ?A‚IUOIO-
i?iyaeaiee iae?iiaoee – 7,5 ian. (io 3 iaaaeu ai 29 ia- „E?, 616.72–002.77–08.
19. Cohen S, Weaver A, Schiff M, Strand V. Two–year treatment of active RA with lefluno-
nyoaa). Anai aieuiui i?iaiaeeanu niioonoao?uay oa-
mide compared with placebo or methtrexate. Arthritis rheum. 1999; 42: Abstract.
?aiey ?acee?iuie i?aia?aoaie, a oii ?enea i?ioeai-
20. Sciff MN, Strand V, Oed C, Loew–Fridirrich I. Leflunomide: efficacy and safety in clin-
aeaaaoe?aneea n?aanoaa (4), noaoeiu (2), aeuieo?ei (1). ical trials for the treatment of RA. Drugs today. 2000;36:383–394.
Iinea ioiaiu eaoeoiiieaa o iieiaeiu iaoeaioia nei- 21. American College of rheumatology, Erik Matteson, John J.Cush. Reports of leflu-
ioiiu iae?iiaoee oiaiuoeeenu, o inoaeuiuo nio?aiy- nimide hepatotoxicity in patients with RA. 2001.
22. c.C. oE?OO‚, a.A. oEEO‚, O.C. a„OIIEI E OO‚U. «cO‚?E ·AEOI?E O?AO?U
eenu aac ia?anoaiey. E ni?aeaie?, ec aaiiuo niiaua-
I? IA?AIE? ?A‚IUOEIO„O ?U?EU – A?‚ (IAUIUIOIE): OO?U IIO„OIAO??IO„O
iee o?oaii iiiyou naycu aaiiie iaoieiaee n i?eaiii
O?EIAIAIE?». eaU, 2004, UOI 12, 2, OU?. 124–128.
A?aau eee n i?iyaeaieai niioonoao?ueo caaieaaaiee 23. a?AI? A.A., AOIOUEI O.C., aIA‚OI? a.a., e?UOIEI a.e., oE?OO‚ c.C. e·?AI-
(aeaaao, aoa?ineea?ic). UE‚EA?E? O?O?‚IAIEE eA, ??IUA?EAU??E? A„O ?‚OI??E?. I. aAUO IOIE?AOU‚AIIOE
Oaeei ia?acii, A?aaa yaeyaony yooaeoeaiui aa- O?AIIE ‚??EAIIOOUE ?A‚IUOEIO„O ?U?EU E UAIOO‚ A„O O?O„?AOOE?O‚IE? ‚ OU-
OU‚? IEOUAE E OUOO. COO?. ?A‚IUEAI 1981;3:11–15.
ceniui n?aanoaii ea?aiey aieuiuo ?A. ?anoioa ?ac-
24. Felson DT., Anderson J., Boers M. et. al. ”The American College of Rheumatology
aeoey yooaeoa e ?anoioa ?acaeoey neiioiiia iaia?aii-
preliminary definition of improvement in rheumatoid arthritis” Arthr. Rheum., 1995, V.38:
neiinoe i?aeoe?anee ia caaeneo io aic?anoa aieuiuo, 727–735
oioy i?aia?ao a iaoae a?oiia aieuiuo ?aua i?eoeinu 25. Van Leeuwen MA, van Rijswijk MH, Sluter WJ et al. Individual relationship between
ioiaiyou ec–ca iaia?aiineiinoe o iaoeaioia noa?oa progression of radiological damadge and the acute phase response in early RA. J
Rheumatol 1997;24:20–7.
50 eao.
26. cOOIO‚ O.a., oE?OO‚ c.C., A?IO‚ A.A. E OO‚U. aIEIE?AOIOA AI?AIEA e–?A-
IUE‚IO„O ·AII O?E eA (O·AO? IEUA?UU?? E OO·OU‚AII?A II?A).
aEUA?UU? aIEI.aA.1997;6:34–36.
1. AI·IO‚ e.a. «eA‚IUOEI?E ?U?EU» ‚ eUIO‚OOU‚A OO ?A‚IUOIO„EE a.,
27. Van der Heijde D.M.F.M, van`t Hof M.A, van Riel P.L.C.M, van Leeuwen M.A, van
1997
Rijswijk M.H, van de Putte L.B.A. Validity of single variables and composite indices for
2. cOOIO‚ O.a. “cAOUA?OEI?A O?OUE‚O‚OOOIEUAI?I?A O?AO?U? O?E ?A‚IUE?A-
measuring disease activity in RA. Ann Rheum Dis 1992;51:177–181.
OIE? A·OIA‚IE??: OUI?U IA?AIE?”. eUOOIEE IAE?EIOIEE EU?II, U 9, 7–8,
28. Smolen J.S, Breedveld F.C, Eberl G, Jones I, Leeming M, Wylie G.L, Kirkpatrick J.
2001, 265–270.
Validity and reliability of the twenty–eight–joint count for the assessment of RA activity.
3. oE?OO‚ c.C. «aA?AIEA ?AIE?I?? ‚?EIUO‚ UA?AIE? ?A‚IUOEIO„O ?U?EU»
Arthritis Rheum 1995;38:38–43.
aOOIO‚OIEE IA. EU?II, 1997, 1, 21–26
29. Prevoo M.L.L, van`t Hof M.A, Kuper H.H, van Leeuwen M.A, van de Putte L.B.A, van
4. Berner B, Akca D, Jung T, et al. Analysis of Th1 and Th2 cytokines expressing CD4+
Riel P.L.C.M. Modified disease activity scores that include twenty–eigth–joint counts.
and CD8+ T cells in rheumatoid arthritis by fiow cytometry. J Rheumatol 2000;27:1128.
Arthritis Rheum 1995;38:44–48.
5. C.M. Weyand. New insights into the pathogenesis of rheumatoid arthritis. J Rheumatol
30. Van Gestel AM, Prevoo MLL, van’t Hof MA, van Rijswijk MN, van de Putte LB, van
2000;39:3–8.
Riel PLCM. Development and validation of the European League Against Rheumatism
6. Breedveld FC. New insights in the pathogenesis of rheumatoid arthritis. J Rheumatol
response criteria for RA . Arthritis Rheum. 1996; 39:34–40.
1998;53:3–7.
31. aEE‚IAIEA ??OAEE I A?‚A
7. Chervinski HM, Coln Rg, Cheung P, Webster DJ, Xu Y–Z, Caulfield JP, et al. The
32. AE I A?‚A
immunosuppressant Leflunomide inhibits lymphocyte proliferation by inhibiting pyrimi-
33. Carulli M.T. “Peripheral neuropathy: an unwanted effect of leflunomide?”
dine biosynthesis. J Pharmacol Exp Ther 1995;275:1043–9.
Rheumatology? 2002? 41: 952–953
8. Siemasko KF, Chong ASF, Williams JW, Bremer EG, Finnegan A. Ragulation of B cell
34. K. Martin., F. Bentaberry, C. Dumoulin et.al. “Neuropathy associated with leflunomide:
function by the immunosuppressive agent leflunomide. Transplantation 1996;61:635–42.
a case series” Ann. Rheum. Dis., 2005, 64: 649–650




524 13, 8, 2005

<<

. 2
( 2 .)