関節リウマチリウマチ（RA） （RA）（RA）診療 …

1 RA RA 65 I 5 III 30 II

2 50% Emery Emery 3 MTP MCP or 30 3 MTP MCP or 30 RA ACR ACR 3 X 3 X 7 4 RA RA RA MRI CCP RF MRI MRI CCP RF MRI MRI 3 5 Early RA CCP CCP RA 80 80~90% RF 50~70 80~90 RF 20% RA overlap

3 ( ) RA 80 80~90% RF 50~70 80~90 RF 20% RA overlap ( ) MMP-3 -3 MMP-3 -3 MMP MMP-3 RA MMP MMP-3 RA MMP-3 CARF lgG-RF RF Modified Sharp Modified Sharp = Erosions.

4 0 = 1 = 5 = 50% 0-10 40 44 van der Heijde, MFM. Bailliere s Clin Rheum. 1996;10:435 JSN :0= 1= 2= 50 3= 50 4= The Window of Opportunity The Window of Opportunity Quinn Emery RA The Window of Opportunity DMARDs DMARDs Gold Sodium Thiomalate Auranofine D-penicillamine Bucillamine Gold Sodium Thiomalate Auranofine D-penicillamine Bucillamine (GST: )(AU )(DPC )(BUC ) SSZ EN ATR MTX TAC: (GST.)

5 (AU )(DPC )(BUC ) SSZ EN ATR MTX TAC: DMARDs RA DMARDs RA 2004 MTX Anchor drugMTX Anchor drugRA MTX

6 MTX MTX 1000 1000 5mg <10mg DMARDs, NSAIDs DMARDs DMARDs, NSAIDs QOL RA DMARDs 30 60mg Biologics( ) Biologics( ) RA NF- IL-6 IL-1 RA Smolen JS.

7 Nature Reviews Drug Discovery 2,2003 RA RA TNF- IL-6 IL-1 RANKL/ODF RA TNF- IL-6 IL-1 RANKL/ODF RA TNF (Tumor Necrosis Factor) 17kDa( 3 ) 26kDa( ) 1. IL-1 IL-6 IL-8 2. 3. ICAM-1 VCAM-1 ) 4. B-1 TNFTNFTNFTNF TNFTNFTNFTNF Biologics Infliximab INF IFX Remicade TNF Etanercept ETA ETN Enbrel TNF receptorAdalimumab ADA Humira TNF Tocilizumab MRA Actemra IL-6 Anakinra Kinerret IL-1 Rituximab RTX Rituxan B CD20 Abatacept (ABA Orencia)

8 CD80/86 6 6 CRP ESR 28mm/hr 6 X 6 6 CRP ESR 28mm/hr 6 X 65 70 65 70 Remicade : Infliximab Remicade : Infliximab TNF TNF TNF TNF ( ) ASPIRE ACR 54 ASPIRE ACR 54 W et al.

9 Arthritis Rheum. 2004;50:3432. +MTX (3mg/kg)+MTX (6mg/kg)+MTX543221624633663750020406080 ACR20 ACR50 ACR70(%)p= p= < < p< 03054 04213 ASPIRE 54 ASPIRE 54 vdH-Sharp (point) MTX 3mg/kg)+MTX 6mg/kg)+MTX W et al. Arthritis Rheum. 2004;50 < < Infusion Reaction 26 26 Enbrel Etanercept Enbrel Etanercept TNF- TNF TNF LT TNF ( ) van der Heijde D.

10 Et al.,Arthritis Rheum;56(12 :3928-3939, n=223 MTX+ n=190051015202530354045(%) p vs MTX p vs 1 DMARD(MTX ) RA 682 MTX 25mg ( 2 ) 25mg( 2 ) MTX 3 MTX 20mg TEMPOTEMPO DAS28< < TEMPO 3 van der Heijde D. et al.,Arthritis Rheum;56(12):3928-3939,2007. 86420-2123 MTX n=210 n=211 MTX n=217 ** * p< vs MTX p< vs MTX p< vs 1 DMARD(MTX ) RA 682 MTX 25mg ( 2 ) 25mg( 2 ) MTX 3 MTX 20mg TEMPO 3 TEMPO 3 MTX 1 8mg TNF- TNF.)