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'+%2-1&/1)1 !#TNFα" 201889 .0$1, (1*2

+%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

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Page 1: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

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Page 4: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

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toxic epidermal nercrolysis(�� TEN) ��

Cytotoxic T lymphocyte–mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs) ����T���������������

Page 5: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

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J Invest Dermatol. 2017;137(5):1004.

Arch Dermatol 1993; 129:92.

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J Clin Epidemiol.1996;49(7):769.

Am J Clin Dermatol. 2012 Feb;13(1):49-54.

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J Invest Dermatol. 2017;137(6):1240.

Br J Dermatol 1666575-600, 2012.

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• CDB��� ; ���� ?*9>J Am Acad Dermatol. 2013;69(2):187.e1.

Watanabe et al. Eur J Dermatol

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Int J Dermatol. 2008 Feb;47(2):180-2.

Crit Care Med. 2014;42(1):118.

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SCORTEN

Kaplan-Meier analysis of survival of patients with TEN based upon SCORTEN score, calculated within 24 hours of hospital admission.

J Invest Dermatol. 2006 Feb;126(2):272-6.

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J Invest Dermatol. 2006 Feb;126(2):272-6.

Burns. 2017;43(1):200.

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Mayo Clin Proc. 2010;85(2):131.

Clin Pharmacol Ther. 2010 Jul;88(1):60-8.

J Dermatol. 1997;24(11):726.Int J Paediatr Dent. 2004;14(3):204.Pediatr Infect Dis J. 2001;20(2):219.

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Curr Opin Allergy Clin Immunol. 2013 Aug;13(4):330-6.

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Allergol Int. 2016;65(1):74.

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Indian J Dermatol Venereol Leprol. 2013;79(4):506.

Br J Dermatol 163S847-853, 2010.J Am Acad Dermatol 71S941-947, 2014.

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BACKGROUND•��3��/4TNFα6AOJNPDQ<�5CTL!�C=I?=Q#BM?=Q#��"��FQK@�(SJS-TEN��2��*;.&9#� 1��4��3��($:

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Ann Pharmacother. 2007;41(6):1083–1084.J Investig Allergol Clin Immunol. 2013;23(1):61–63.

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Drugs.2014;74(12):1379–1410.

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Methods

Page 36: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

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Treatment

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Inclusion criteria• 2�������+� '

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Inclusion criteria (SJS-TEN���)Score A(1)'/#(),/%+.(2)�����(3)*$-&"/����(4)BSA110%�������15cm(5)���(6)�� ��� ��00 0 10 1-2 20 3-6

• Score A � B !final score���

• Probable � defineite!inclusion

2egiSCAR��

Score B

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Inclusion criteria

• ���!*��02:1'(��0inclusion• ��"�-� 0�),%(.$�&/(��*9;57*��"�+'(

≪� ≫GNLY � 3968:4;IIF �#������DIF �������Histopathology ������

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Exclusion criteria

ü ���(" ' ��&�

ü TNFα���-54/7�

ü CXR%)*��(" '����&��,

�!$(&

ü ��(" '�����,�#+(&

ü HBV�HCV�

ü HIV��(" 'CD4<200&(&

ü 0623.-61���

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•*�>exclusion criteriaA33<;�0F95CstudyK +>4@1�C��B��Q�AMNPLO��?����RK#2�,?9;

•�-8J;�!C:D=�.�!

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•&�S�@5?F2���B /(�@�"��AGH&�8J=1I

Q�&�!B���C%)K'E@3<;R

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outcomeØPrimary outcome

��������

��������

ØSecondary outcome���3����follow up���

Vital sign ��

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� ��• =MFLN?Q5TNFαT ELISA�

�+ <BGOAJD @CP;E

acuteT6��� 4.3.1.7 5.1.2.5maximalT��( �,� 9.1.4.7 8.4.5.8lateT��6 $���� 14.3.6.2 16.0

• TregT%�)-8��7� /��':��!"4-196℃94�#0Treg8� TPERPerCPRAPC-RCy7�*�HD��44℃330�+W[XUZ\VY1�&

2FITC�*�HDFOX34�&3IPS>;DKSBS4��

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Treg1���T��')2• FOXP3���-��$,Treg) �

���-��# ���*����� -��$,

• FOXP3(��0./*Treg(����"TNFα���&�#%��!+

J Immunol.2009;182(12):8071–8079.

http://www.riken.jp/pr/press/2017/20170802_1/Blood. 2006;108(1):253–261.

J Exp Med.2004;200(3):277–285.

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Statistical Analysis• 7�VXW_GraphPad Prism5]Graph Pad Software^

• Primary outcomeKaplan-Meier�1_.3\04*�N��M6DF�>A

�.�' N=��>

• Secondary outcomeZ � _22>";]��(A!�&A�2N+�";N�@/^X² �_32>";]04*�^t � _2GN#,2>";]SCORTEN7�A�2N+�";N�@/A

�)�-���^

• P� 0.05�%I��J�

�7��$]ITTQPer ProtocolLK^QA�NU[YZ�9�N8<O:PE→�?MOAPer protocol7�T�5CSHBR

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ü Study approval : CGMH#�����$�� ���"����!

ü ��

������

ü��� �����COI���

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Results

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2009-2015��96���

���#�"��CD4<200��� �����

Figure 2. Flow chart for the selection of study participants.

��� ���� 48� ��!��� 45�

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Baseline�������

2���������

Page 52: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

SCORETEN�����

������� �

Page 53: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

Primary outcomeØ����$��BSA≧107$SJS-TEN#���$',/35.41�� *(�����)8�SJS-TEN % "��&����%11�vs11�9

�����$��,/35.41�!-06+2� "�

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��������

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Page 55: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

�� �"&(!'$� 8.3* #)�%� 16.3*���������

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�������

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Page 57: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

Ø ��4$(-1'.+������� �� !��������

(p=0.026)4&)3#,���� �������"������

(p=0.280)

� CGMH �SJS-TEN 2%&+0*5(/5&62001 -20087���*5(���

Page 58: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

Ø SJS-TEN���������������������2�������

Page 59: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

��������TNF��

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Figure 4. Immunological effects in SJS-TEN patients with 10% or greater BSA detachment after etanercept or corticosteroid treatment.

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Page 60: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

Figure 4. Immunological effects in SJS-TEN patients with 10% or greater BSA detachment afteretanercept or corticosteroid treatment.

Treg���

BSA 10%���SJS-TEN����������������������Treg ����

Page 61: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

Discussionü*&$+���; .0�6("*��

ü*&$�+7,?MILM<AQ6��O>LORDR2-83�:98

ü@NE@BFP<H3�/1,=DJNCKG7,!) ���6)%)�*#&2,��4����S' �������T5��4�;��/0

Page 62: +%2-1&/1)1 ! # TNFα · sjs-ten •1 *100 #&02-7 •hiv , +100 543%#1 • %2 , +2 543%#1 •sle ,1.2%( (0.02 0.05%)* -!$ • , .)$ • + 6sjs', 3.4%"ten', 19%

ü���=79�(EV3JYM=@>?UA���)F�GH�RZYOCXIQF�ENM

ü\^`b]a_'T5�T��(UA<6:;=79F5PBWA0$�S2-KOCXIQ[&

ü=@>?T�UA\^`b]a_ %�T"��(�OSDCO��JYMFA���(PU��JYRENM

ü=@>?T���F�KC0$�(PUA\^`b]a_T#1�[�+QLX�)�FBX

üKEKA�!S.*LX0�<8<4=79�(T\^`b]a_T�/�#UAJVRX,�F�+

J Immunol.2009;182(12):8071–8079.

Discussion

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Limitation

ü SJS-TEN6100��40.4-0.65��1';���*3(

ü @LIJ@>B*+,=7���:� �*0(.�"�';

üSCARM6#��1'<.9&���4����585�$6��1+3)/.

ü?DHJCIF6 ��&2AEK>G6��1';&-5.94%!�41+3)/.

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ConclusionüTY^dX_[K9�H����F:P

üTY^dX_[K9WZfS\G�+AE9�$ =O, J313.4/2J '���-R!&A9�%�*J���J���K�=DC

ü�$ =O, J313.4/2JUb]acVg<NL420.8Je`dR��@B94756R��@BP?GR�O=IAC

ü?J"#K9313.4/2J��I<>P4208��)J(���J��IHP=MAQH;

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��!��

Yes

Per Protocol Analysis26%(25/96)�&'$%� ��

Yes

Yes

NO

� ������!��"�#�������� ���"��"���NNT"����

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"n�*J?O�kn[�t�6

 �G�¥b�SJS-TEN�rp�m�������������3=�2�m

��:�$q~~m@S;��3>)d�BNwz��Q so�

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 hA/�\j�o�£ �����g5m�������@�5�A/��Q��¤

 �V�������s���Z�w�{CF���p

  Per ProtocolX-���K.¡������mM'�26%sRU¢ +!��]�{K.��n11y~�f�w�{2_�au�p LY#4�m�K.s0W ���}�p�v�s�%|s�(D

 [P�o�@SE�sA/�w��p�p�Q

 ^<�m1�8m�@�9��c�)dm@S HT;��&��

+7�ex��+!��]��p�p

  �����i¡2`d�m�������£I6��m����� 6000�¢

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%Zo0B<F�Wnxz|~y}{n�fu�G#

�2O)jr4�o�apYSCORTEN 3�5oS;

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4�nTfuKaplan-Meier.DoMPmaY �<m4�*(p�,�

→ �o��jpYSCOTEN 3��o4�pY20*��n50%p4�

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X%Zo0BCO

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Q�3N_!L

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gvu

J Invest Dermatol. 2006 Feb;126(2):272-6.

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