Romatoid artrit tedavisinde T hücre hedefli tedaviler Yusuf Yazıcı, MD Assistant Professor of Medicine, NYU School of Medicine Director, Seligman Center for Advanced Therapeutics NYU Hospital for Joint Diseases ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Danışmanlık/konuşmacı BMS Celgene Centocor Genentech Pfizer Roche UCB ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
İlk çalışmalar LTE verileri Erken RA da abatacept DMARD kullanmamış Hasta takibi Biz (ben) ne yapıyoruz? ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
101-100 ACR Responses - 5 Years Study 101-100: MTX Inadequate Responders Patients treated with Abatacept + MTX 100 Doubleblind phase* Open-label LTE phase* ACR responses (%) 80 60 40 20 77% 53% 29% 81% 60% 31% 76% 56% 33% 73% 42% 32% 83% 65% 40% ACR 20 ACR 50 ACR 70 0 n=83 n=72 n=63 n=59 n=52 0 1 2 3 4 5 Years ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
DAS28 Through 5 Years Study 101-100: MTX Inadequate Responders 100 Double-blind Open-label LTE Patients achieving disease activity score (DAS28) (%) 80 60 40 20 0 DAS28 3.2 (low disease activity) 48% 25% 51% 28% 0 1 2 3 4 5 Year 50% 27% DAS28 2.6 (remission) 57% 37% 59% 45% n=83 n=72 n=64 n=60 n=53 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
AIM Trial Design AIM Trial: MTX Inadequate Responders Nearly half of all patients on Abatacept achieved remission (defined as DAS28 <2.6) at 5 years Double-blind phase 1 Open-label LTE phase 2 Abatacept + MTX (n=433) Patients were randomized 2:1 to study arm Placebo + MTX (n=219) Abatacept + MTX (n=378) Placebo to Abatacept + MTX (n=161) Day 0 Year 1 Year 2 Year 3 Patients had active disease despite receiving MTX 10 swollen joints (66 joint count), 12 tender joints (68 joint count) CRP serum levels 1.0 mg/dl and 3 months on MTX, ( 15 mg/week) Patients received stable dose of MTX for >1 month prior to randomization Patients underwent washout of other DMARDs 1 month prior to randomization 1 Kremer JM, et al. Ann IntemMed. 2006;144(12):865-876 2 Kremer JM, et al. Oral Presentation. ACR 2007. THU699
Abatacept in patients with an incomplete response to methotrexate Placebo + MTX (n=214) Abatacept 10 mg/kg + MTX (n=424) 80 70 * 68 6 months * 12 months 80 73 70 Patients (%) 60 50 40 30 20 40 17 * 40 * 20 Patients (%) 60 50 40 30 20 40 18 * 48 * 29 10 7 10 6 0 0 ACR 20 ACR 50 ACR 70 ACR 20 ACR 50 ACR 70 Kremer J, et al. Ann Intern Med 2006;144:865 876. *p<0.001 vs placebo + MTX; p<0.001 vs abatacept at 6 months. MTX=methotrexate; ACR=American College of Rheumatology. 10
ACR Responses Through 3 Years AIM Trial: MTX Inadequate Responders Patients treated with Abatacept + MTX 100 Double-blind LTE Patients achieving ACR response (%) 80 60 40 20 0 73% 39% 15% Months 73% 44% 22% 82% 54% 32% 0 4 6 1 2 3 Years ACR 20 367 371 373 337 303 ACR 50 368 373 372 338 306 ACR 70 371 374 374 340 309 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 88% 61% 39% 85% 63% 38% ACR 20 ACR 50 ACR 70
DAS28 Improvements Through 3 Years AIM Trial: MTX Inadequate Responders More than one-third of all Abatacept patients achieved remission (defined as DAS28<2.6) at 3 years* 100 Double-blind LTE Patients achieving DAS28 (%) 80 60 40 20 0 DAS28 3.2 (low disease activity) 44% 25% 52% 28% DAS28 2.6 (remission) 0 1 2 3 Year 53% 37% (n=378) n=370 n=337 n=299 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Abatacept Inhibited Radiographic Progression Through 3 Years AIM Trial: MTX Inadequate Responders Mean change from baseline in Genantmodified Sharp Score 4 3 2 0 0.89 1 Total Score 0 1 2 3 Year Genant-modified total Sharp score range (0-290) Abatacept + MTX Placebo + MTX Placebo to Abatacept + MTX Mean Changes: 0.692 1.76 2 0.25 1 1 0.43 1 n=304 n=293 n=302 n=132 n=129 n=131 At randomized baseline radiographic scores were 45.2 vs 47.3 Sharp units for Abatacept + MTX and placebo + MTX, respectively for patients who entered the LTE From baseline to Year 1, 46% of patients on Abatacept + MTX (n=304) had no radiographic progression* vs 35% on placebo + MTX From Year 1 to 2, 57% of patients on Abatacept + MTX (n=297) had no radiographic progression From Year 2 to 3, 63% of patients on Abatacept + MTX (n=295) had no radiographic progression ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 0.36 2
OP-0248 BIOLOGIC NAÏVE EARLY RHEUMATOID ARTHRITIS (RA) PATIENTS TREATED WITH ABATACEPT ACHIEVE GREATER DISEASE REMISSION COMPARED TO RA PATIENTS WITH LONG STANDING DISEASE, WITH NEARLY HALF OF EARLY RA PATIENTS IN DAS28 REMISSION AT 3 YEARS An Exploratory Post-hoc Analysis Y. Yazici, 1 D. Moniz Reed, 2 C. Klem, 2 L. C. Rosenblatt, 2 G. Wu, 2 J. Kremer 3 1 Rheumatology, NYU Hospital for Joint Diseases, New York; 2 Rheumatology, Bristol-Myers Squibb, Princeton, NJ; 3 Center for Rheumatology, Albany Medical College, Albany, NY. ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 14
Methods AIM Study Phase IIb Study (101-100) Double-blind period (12 months) 1 = Primary objectives American College of Rheumatology (ACR) 20 at 6 months Health Assessment Questionnaire Disability Index (HAQ-DI) improvement of 0.3 at 1 year Erosion score at 1 year Open-label long-term extension (LTE) 2 Double-blind period (12 months) 3 = Primary objective To compare the clinical efficacy of two doses of abatacept + MTX vs placebo + MTX in subjects with active RA currently receiving MTX, as assessed by ACR20 at 6 months Open-label LTE 4 = Primary objective Assess safety and tolerability Evaluate long-term efficacy and safety 1 Kremer JM, et al. Ann Intern Med. 2006;144(12):865 876; 2 Data on file. ABAT 001. Bristol-Myers Squibb Company, Princeton, NJ; 3 Kremer JM, et al. NEJM. 2003;349:1907 1915; 4 Data on File. ABAT 009. Bristol-Myers Squibb Company, Princeton, NJ. 15
100 ACR 20 responders (%) 80 60 40 20 0 ACR 20 Response Rates Double-blind phase 87.7 86.6 79.9 Open-label LTE phase 79.7 Abatacept (~10 mg/kg) + MTX Early RA ( 2 years duration) 83.3 80.7 Long-standing RA ( 10 years duration) 0 1 2 3 Year Patient population size Year 1 Year 2 Year 3 Early RA ( 2 years duration) 106 97 88 Long-standing RA ( 10 years duration) 139 123 108 16
ACR 50 Response Rates 100 Double-blind phase Open-label LTE phase ACR 50 responders (%) 80 60 40 20 0 58.5 60.8 48.2 53.2 Abatacept (~10 mg/kg) + MTX 62.5 57.7 0 1 2 3 Year Early RA ( 2 years duration) Long-standing RA ( 10 years duration) Patient population size Year 1 Year 2 Year 3 Early RA ( 2 years duration) 106 97 88 Long-standing RA ( 10 years duration) 139 124 111 17
ACR 70 Response Rates 100 ACR 70 responders (%) 80 60 40 20 Double-blind phase Open-label LTE phase Abatacept (~10 mg/kg) + MTX * Early RA ( 2 years duration) Long-standing RA ( 10 years duration) 36.8 39.2 44.3 32.3 30.4 25.0 * 0 *p<0.05 vs patients with long-standing RA ( 10 years duration). 0 1 2 3 Years Patient population size Year 1 Year 2 Year 3 Early RA ( 2 years duration) 106 97 88 Long-standing RA ( 10 years duration) 140 124 112 18
Low Disease Activity Score DAS28(CRP) 3.2 100 Early RA ( 2 years duration) Long-standing RA ( 10 years duration) LDAS responders (%) 80 60 40 20 51.4 41.0 53.6 45.9 59.8 52.7 0 Year 1 Year 2 Year 3 Abatacept (~10 mg/kg) + MTX. ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 19
100 Significantly More Early RA Patients Achieved DAS28-defined Remission Early RA ( 2 years duration) Long-standing RA ( 10 years duration) DAS28(CRP) remission (%) 80 60 40 20 35.2 ** 32.0* 19.4 19.7 46.0* 30.9 0 Year 1 Year 2 Year 3 *p<0.05; **p<0.01, vs patients with long-standing RA ( 10 years duration). Defined as DAS28(CRP) 2.6. ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 20
AIM: 3-year Radiographic Outcomes 3.0 Mean change from baseline in mtss 2.0 1.0 0.0 3.0 2.0 1.0 0.0 Disease duration 2 years n=19 n=73 Δ=2.07 Δ=1.07 Placebo (to abatacept) + MTX* Abatacept + MTX Δ=0.58 n=20 n=71 Δ=0.54 *Patients in the placebo group were switched to abatacept + MTX after Year 1. MTX=methotrexate; mtss=genant-modified total Sharp score; Δ=mean change. n=19 n=73 1 2 3 Year Disease duration 10 years n=53 n=100 Δ=1.48 Δ=0.60 Δ=0.60 Δ=0.45 n=54 n=100 n=54 n=99 1 2 3 Year Δ=0.26 Δ=0.22 Δ=0.62 Δ=0.12 21
AIM: 3-year Radiographic Outcomes Cumulative Distribution of Changes 50 Disease duration 2 years Change from baseline 40 30 20 10 Abatacept + MTX Year 3 Year 2 Year 1 0-10 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Cumulative probability ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 22
AIM: 3-year Radiographic Outcomes Cumulative Distribution of Changes 50 Disease duration 10 years Change from baseline 40 30 20 10 Abatacept + MTX Year 3 Year 2 Year 1 0-10 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Cumulative probability ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 23
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Abatacept in patients failing tumor necrosis factor antagonists: efficacy at Month 6 Patients (%) 60 50 40 30 20 10 0 20 Placebo (n=133) ACR response rates * 50 4 * 20 2 Abatacept ~10 mg/kg (n=258) 10 ACR 20 ACR 50 ACR 70 Patients (%) Patients (%) 20 15 10 5 0 50 40 30 20 10 3 * 17 Improvement in HAQ 0.3 points * 23 DAS scores <3.2 Low disease activity 47 1 * 10 <2.6 Remission Adapted from Genovese MC, et al. N Engl J Med 2005;353:1114 1123. *p< 0.001 vsplacebo; p< 0.01 vsplacebo. ACR=American College of Rheumatology; DAS=disease activity score; HAQ=Health Assessment Questionnaire. 25
ACR responses through 3 years with abatacept: ATTAIN Trial ACR responses (%) 100 80 60 40 20 0 60% n=208 24% n=209 12% n=212 65% n=198 32% n=201 18% n=202 0 6 months 1 2 3 Year 75% n=156 46% n=153 23% n=155 82% n=110 ATTAIN ACR 20 54% n=112 ACR 50 ACR 70 26% n=113 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Remission (Defined as DAS28 <2.6) and LDAS Through 3 Years With Abatacept: ATTAIN Trial DAS28 responders (%) 100 80 60 40 20 0 Double-blind phase 18% 11% 24% 14% Open-label LTE phase* Low disease activity (defined as DAS28 3.2) Remission (defined as DAS28 2.6) n=208 n=194 n=153 n=109 0 6 months 1 2 3 Year 32% 20% 39% 24% ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Agree Trial Design AGREE Trial: Early Moderate to Severe RA Active control trial Key inclusion criteria Early RA 2 years, MTX naïve, 1 erosion, RF+ or anti-ccp-2+ Double-blind phase Abatacept + MTX (n=256) Placebo + MTX (n=253) Open-label LTE phase (ongoing) Abatacept + MTX Day 1 Year 1 Year 2 Screening Randomization 1:1 Co-primary endpoints: 1. Remission Defined as DAS28(CRP) <2.6 2. Radiographic progression Assessed by Genant-modified total Sharp score Key secondary endpoint ACR 50 Major Clinical Response (6 months of consecutive ACR 70 response) DAS28 (CRP) Physical function (HAQ-DI) Health-related QOL (SF-36 ) ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Baseline Demographics and Clinical Characteristics AGREE Trial: Early Moderate to Severe RA Patients in the AGREE Study had short disease and highly active disease Abatacept + MTX (N=256) Placebo + MTX (N=253) Age, mean years (±SD) 50.1 (12.4) 49.7 (13.0) Gender, % female 76.6 78.7 Race, % Caucasian 78.9 86.6 Disease duration, mean months (±SD) 6.2 (7.5) 6.7 (7.1) Tender joints, mean (±SD) 31.3 (14.8) 30.8 (14.0) Swollen joints, mean (±SD) 22.9 (11.3) 21.9 (10.1) DAS28 (CRP), mean (±SD) 6.3 (1.0) 6.2 (1.0) HAQ-DI 0-3, mean (±SD) 1.7 (0.7) 1.7 (0.7) ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Baseline Demographics and Clinical Characteristics AGREE Trial: Early Moderate to Severe RA Patients in the AGREE Study had multiple markers of poor prognostic features Abatacept + MTX (N=256) Placebo + MTX (N=253) Rheumatoid factor positive, n (%) 246 (96.1) 245 (96.8) Anti-CCP2 positive, n (%) 236 (92.2) 217 (85.8) TSS, mean (±SD) 7.5 (9.7) 6.7 (8.8) CRP mg/dl, mean (±SD) 3.1 (3.1) 3.6 (5.0) CCP2 = Cyclic citrullinated peptide 2; TSS = Genant-modified total Sharp score ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
High Retention Rates in the AGREE Study AGREE Trial: Early Moderate to Severe RA Percentage of patients (%) Through 1 year, no patients on Abatacept discontinued due to lack of efficacy 100 80 60 40 20 0 0.8% 0.8% 0.8% 0.4% 90.6% 0.4% 89.7% 2.7% 3.5% 0.0% Pregnancy Lost to follow-up Death No longer meets study criteria Abatacept + MTX Placebo + MTX n=256 n=253 Data are based on an intent-to-treat analysis for patients initiated on Abatacept + MTX or placebo + MTX ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 0.0% 0.4% 0.8% 0.0% 0.4% 1.2% 4.3% 3.2% Other Withdrawal of consent Adverse event Lack of efficacy
Significantly More Patients on Abatacept Were in Remission at 1 Year as Defined by DAS28(CRP) <2.6 AGREE Trial: Early Moderate to Severe RA Co-Primary Endpoint Proportion of patients in DAS28-defined remission 100 *P<0.001 Patients in DAS28 Defined Remission (%) 80 60 40 20 41.4%* 1.8x more patients 23.3% Abatacept + MTX (N=256) Placebo + MTX (N=253) 0 Year 1 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Abatacept Significantly Inhibited Radiographic Progression AGREE Trial: Early Moderate to Severe RA Co-Primary Endpoint Mean change from baseline in Genant-modified TSS 1.2 0.8 0.4 0 0.63 P=0.040 Year 1 Abatacept + MTX (n=242) Placebo + MTX (n=242) Genant-modified total Sharp score range = 0 to 290 Baseline radiographic TSS were 7.5 for Abatacept + MTX vs 6.7 Sharp units for placebo + MTX 1.06 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
ACR Responses Through 1 Year AGREE Trial: Early Moderate to Severe RA Abatacept demonstrated significant and meaningful improvements in ACR scores at 1 year in patients with early RA 100 *P<0.001 Patients achieving ACR response (%) 80 60 40 76%* 62% 57%* Abatacept + MTX (N=256) Placebo + MTX (N=253) 42% 43%* 27% 20 0 ACR 20 ACR 50 ACR 70 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Proportion of Patients With Major Clinical Response AGREE Trial: Early Moderate to Severe RA Defined as ACR 70 for 6 Consecutive Months 100 Abatacept + MTX (N=256) Patients with major clinical response (%) 80 60 40 20 27.3% P<0.001 11.9% Placebo + MTX (N=253) 0 Year 1 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
HAQ-DI Responses Through 1 Year AGREE Trial: Early Moderate to Severe RA Patients with clinically meaningful HAQ-DI response (%) 100 80 60 40 20 A significantly greater percentage of patients in the Abatacept arm achieved clinically meaningful improvement* 0 Month * Mean change of 0.3 units from baseline is considered clinically meaningful in this trial 75% ƚ 72%* 64% Abatacept + MTX (n=256) Placebo + MTX (n=253) 62% 0 1 2 3 4 5 6 7 8 9 10 11 12 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri *P<0.05 ƚ P<0.01
Overview of Adverse Events Reported in Year 1 AGREE Trial: Early Moderate to Severe RA Abatacept + MTX (N=256) n(%) Placebo + MTX (N=253) n(%) Deaths 2 (0.8) 4 (1.6) SAEs 20 (7.8) 20 (7.9) Related SAEs 5 (2.0) 6 (2.4) Discontinuations due to SAEs 3 (1.2) 3 (1.2) AEs 217 (84.8) 211 (83.4) Related AEs 98 (38.3) 114 (45.1) Discontinuations due to AEs 8 (3.1) 11 (4.3) ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Serious Infections and Malignancies Reported in Year 1 AGREE Trial: Early Moderate to Severe RA Abatacept + MTX (N=256) n(%) Placebo + MTX (N=253) n(%) Serious infections Total patients with infections and infestations 2 (0.8) 4 (1.6) Cellulitus 1 (0.4) 0 Lung infection pseudomonal 1 (0.4) 0 Pneumonia 0 3 (1.2) Breast cellulitis 0 1 (0.4) Malignancies Total patients with malignancies 1 (0.4) 0 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Probability curves ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 44
Radiographic outcomes in four methotrexatenaïve randomized controlled trials Sharp scale 450 400 350 300 250 200 150 100 50 0 1 1.59 0.54 0.52 2.8 0.4 3.7 1.3 3 5.7 ERA ETA ERA MTX TEMPO ETA+MTX TEMPO ETA TEMPO MTX ASPIRE IFX+MTX ASPIRE MTX PREMIER ADA+MTX PREMIER ADA PREMIER MTX Sharp score Yazici Y, Yazici H. Clin Exp Rheumatol 2008;26:449 452. 45 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Hasta tercihi ve kullanma kolaylığı ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 46
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 47
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 48
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 49
RAPID3 ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 50
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 51
ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri 52
Peki, ben ne yapıyorum? = MDHAQ, RAPID3 Her hasta, her visit = MTX (10mg/qwk), prednisone (2.5-5mg) 3 ay, (25mg), parenteral? = RAPID >12/30 Add TNF, abatacept,3-6 ay = Hala aktif ise? 2. TNF? Rituximab? ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri
Sonuç Erken ve agresif tedavi hedefi MTX ilk DMARD Yeterli cevap olmadığı zaman? Biolojik ajanlardan biri Etanercept İnfliximab Adalimumab Abatacept ANKARA ROMATOLOJİ SEMPOZYUMU Sağlıkta ve Romatizmal Hastalıklarda T Hücreleri