Rituximab in autoimmune diseases

1
Rituximab in autoimmune diseases
2
?????????

• ???????(autoimmune diseases)??????????????????????
  ?????????
• ?????????????????????????????????????????????????
  ??

3
?????????

• ???????????????????(?)???????????????????????(?)?
  ????????????????????,????????????????????

4

• ?????????????????????????????????
• ??????????????????,??????????????(naive
  stadium),???????
• ?T???CD52????Campath 1H???CD20????rituximab???????
  ??

5
????/?????????
?????B??CD20?????
?K???
?IgG1?Fc??????????????
6
???????B??

• 1?????(complement activation)
• 2?ADCC (antibody-dependent cytotoxicity)
• 3?????(apoptosis induction)
• 4??????(antiproliferative effect)
• 5?Fc?????(Fc receptor polymorphism)

7

• Idiopathic thrombocytopenic purpura (ITP)

8
?????ITP

• ??????????2370
• ???????375 mg/m2????
• ?4?
• ??????????

9
(No Transcript)
10

• ????????rituximab??????ITP?????
• 35???(??52?,1782?,17???)?????????????25???????IgG
  ,16?????16??????????????????????,???,CTX,VCR,???,?
  ???
• Rituximab????? 375 mg/m2?????4??CR???PLTgt
  100109/L ,PR?PLTgt 50109/L ,MR?PLT?????50109/L
  ?4??????????,???39?????????

11

• ???????44(17/ 39),7 CR (18),6 PR (15),4 MR
  (10),??CR?PR????9/13???????12??????,???38?????C
  R?PR????????47???????????,??2?????????????????
• Rituximab Chimeric Anti-CD20 Monoclonal Antibody
  Treatment for Adult Refractory Idiopathic
  Thrombocytopenic Purpura Am J Hematol 78275280
  (2005)

12

• New York Presbyterian Hospital?????
• 57?????ITP,????PLTlt 30 x 10(9)/l,??????2?ITP???,31
  ??????
• Rituximab??375 mg/m(2) ???4??
• ????33???1-2?????,1???3?????,??????????B?????0.03
  x 10(9)/l???????????????,???????????

13

• ??31?(54)??,??PLTgt50 x 10(9)/l,??18?CR (CR
  platelet count gt150 x 10(9)/l),13?PR(PR platelet
  count 50-150 x 10(9)/l)?29????????8?????18?CR??16?
  (????28,??8???????),?????72.5????CR?13PR???2???PR
  ?
• ??Rituximab????ITP?????,????????,???32??????????
  ?
• The efficacy and safety of B-cell depletion with
  anti-CD20 monoclonal antibody in adults with
  chronic immune thrombocytopenic purpura. Br J
  Haematol. 2004 Apr125(2)232-9.

14

• Rituximab?????ITP??????????,????????????????
• ?????????????????????????????????
• ????ITP????????????????????????????

15

• Autoimmune haemolytic anaemia(AIHA)

16
Rituximab??AIHA

• ????????????????? ??????
• ???? ????? ?T????????????AIHA

17
(No Transcript)
18

• ??Haugesund County Hospital????
• 6??????????,???????CD20()kappa() B-cell???
• Rituximab??375 mg/m(2), d 1, 8, 15, and
  22,?7????

19

• ??1???CR?4????PR(??1?PR?????????PR)?2????????????
  ???4.1 g/dl,?????????4.7 g/dl?????????,??????????
• Favourable response to therapy with the anti-CD20
  monoclonal antibody rituximab in primary chronic
  cold agglutinin disease. Br J Haematol
  20011157983.

20

• Trape G????
• 5????????????AIHA?
• Rituximab??375 mg/m(2) ?????4??

21
(No Transcript)
22
(No Transcript)
23

• ????????????????????,3???CR?
• Rituximab chimeric anti-CD20 monoclonal antibody
  treatment for refractory hemolytic anemia in
  patients with lymphoproliferative disorders.
  Haematologica 2003882235.

24

• Rituximab??AIHA????,??????????????80???
• ??4???????1???,??????,??????????????
• ??2??????Rituximab?????????,?????Rituximab????????
  ??????????

25

• Rheumatoid arthritis (RA)

26

• ????B?????RA??????????????,Rituximab??B???
• Rituximab???????????RA???B????,?RF???????????B??
  ????????

27

• Ann Rheum Dis2005???????14?RA??rituximab??,??11???
  ????????,?????????,????????
• Tolerance and short term efficacy of rituximab in
  43 patients with systemic autoimmune diseases.
  Ann Rheum Dis. 2005 Jun64(6)913-20.

28

• ?????????????????
• 22?RA?rituximab??B????????????????????
• Serologic changes following B lymphocytedepletion
  therapy for rheumatoid arthritis. Arthritis Rheum
  200348214654.

29

• ???????rituximab??????????????,??????33??????????
  ????CRP???B??????21???????B????????????,??????????
  ?????(range 0-17 months)?

30

• ?????????????????????????
• 40?RA????rituximab??(?????375 mg/m(2)??????4?)
• ??????????,CTX?/?MTX???????B?????????????,????????
  ????T???RA???????????????????
• B lymphocyte depletion in rheumatoid arthritis
  targeting of CD20. Curr Dir Autoimmun.
  20058175-92.

31

• ???Udine???????,5???RA??rituximab??,????????,??MTX
  ?????A??,??2????????alpha?????
• ??2????????????(????American College of
  Rheumatology 70 response ACR70 ?
  ACR50),?????????10???12?????2???ACR20,????5???7???
  ???????CRP?RF?????
• Efficacy of selective B cell blockade in the
  treatment of rheumatoid
• arthritis evidence for a pathogenetic role of B
  cells. Arthritis Rheum
• 200246202933.

32

• Rituximab??RA?????????
• ???????????Rituximab?????????B????RA??????
• ??????,???????,??????????,??????

33

• Systemic lupus erythematosus(SLE)

34

• ??????????????T?????????B??????????
• rituximab??????B??,?B????,?????
• rituximab????????????????????? ?

35

• ??Middlesex Hospital???????
• 6??????SLE,???????????
• ??rituximab 500-mg???????,CTX 750mg???????,??????
  ????

36

• ?????????????????1???3??????????5?????????????Bri
  tish Isles Lupus Assessment Group
  ??SLE?????14?(range 9-27)??6?(range
  3-8)????????,???,????SLE?????????4???????,ESR???
• An open study of B lymphocyte depletion in
  systemic lupus erythematosus. Arthritis Rheum.
  2002 Oct46(10)2673-7.

37

• ??Rochester???Rituximab??SLEI/II????
• ????Rituximab??SLE????????
• ??Rituximab???????100 mg/m2(???),??375
  mg/m2(???),375 mg/m2?????4?(???)?SLE?????(SLAM)???
  ??????

38

• ??Rituximab???????,????????????(11
  /17)???????B????(lt5 CD19 B cells/microl)???????,S
  LAM???????3???????(P 0.0016 ? P
  0.0022)????????Ads DNA????????,????????12???6?????
  ?????(HACAs)????100 ng/ml.?
• ??Rituximab??SLE??,???????B??????????B cell
  depletion as a novel treatment for systemic lupus
  erythematosus a phase I/II dose-escalation trial
  of rituximab. Arthritis Rheum. 2004
  Aug50(8)2580-9.

39

• Rituximab????SLE??????????????,???,??rituximab
  ?SLE???????????

40

• Rituximab??????????????

41
The numbers of patients with autoimmune diseases
treated with rituximab and the results of therapy
42
??

• Rituximab?????????????????375 mg/m2?????4?,???????
  ?B??,?????????
• ??????50???
• ?????????/???????,????????????????????????????????
  ??

43

• ?? !