Table 3

Outcome of steering and drug strategy trials

Steering trials
RCTs
TICORA5 (DAS-steered vs routine care)
 CEULAR good response at 18 months (primary outcome): OR=5.8 (95% CI 2.4 to 13.9); 82% vs 44%p<0.0001
EULAR remission at 18 months: OR=9.7 (3.9 to 23 to 9), 64% vs 16%p<0.0001
ACR70 at 18 months OR=11 (95% CI 4.5 to 27), 71% vs 18%p<0.0001
 FNA
 RMedian (IQR) change in total Sharp Scores at 18 months 4.5 (1–9.87) vs 8.5 (2–15.5)p=0.02
CAMERA6 (intensive steering based on SJC, TJC, ESR and VASpt-pain vs routine care)
 CNumber of patients in remission for 3 months (primary outcome)
 During the fi rst year: 35% vs 14%p<0.001
 During second year: 50% vs 37%p<0.0029
TJC AUC after 2 years 3.6 (1.9 to 6.0) vs 5.5 (2.8 to 9.2), p=0.001p<0.001
SJC AUC after 2 years 2.7 (1.5 to 5.2) vs 4.7 (2.8 to 7.6)p<0.001
ESR AUC after 2 years 17.7 (10.2 to 27.6) vs 21.6 (13.0 to 33.6)p=0.007
ACR50 at
 1 year: 58% vs 43%p<0.01
 2 years: 43% vs 45%NS
 FHAQ-AUCNS
 RAnnual radiographic progressionNS
Median (IQR) change over 2 years 0 (0–2.0) vs 0 (0–2.5) units per year
Fransen et al7 (DAS-steered vs routine care)
 CDAS28≤3.2 at 24 weeks: 31% vs 16% (primary outcome)p<0.028
DMARD changes: 20% vs 9% (primary outcome)p<0.05
 FNA
 RNA
BROSG8 9 (intensive care vs symptomatic care)
 CSJC, TJC, ESR and PGANS
 FHAQ (primary outcome): sign deterioration in both arms: NS between treatment armsNS
 RLarsen scoreNS
van Hulst et al10 (DAS-guided vs routine care)
 CDAS28 mean change after 18 months 0.5 vs 0.65NS
 FNA
 RNA
Non-randomised comparative trials
Allaart et al11 (DAS-steered vs routine treatment)
 CESR median (IQR) at 1 year −19 (−6 to −37) vs −13 (−3 to −28)p=0.011
DAS28 (target) mean at 1 year −2.7±1.5 vs −1.9±1.5p=0.001
 FHAQ mean change after 1 year −0.7±−0.7 vs −0.5±−0.7p=0.029
 RNA
Stenger et al12 (CRP-steered high-risk/low-risk vs routine care high-risk/low-risk)
 CAUC for CRP (target) lower in intensive group after 2 years
 High-risk patientsp=0.002
 Low-risk patientsp=0.20
 FNA
 RSHS median (IQR) progression rate after 2 years
 High-risk patients 26.0 (range 0–100) vs 35 (1–188)p=0.03
 Low-risk patients 11.0 (0–87) vs 8.0 (0–99)p=0.36
van der Woude et al13 (DAS-steered vs routine care)
 CDAS<1.6 (remission) after 5 years 9% vs 11%NS
 FNA
 RNA
RCTs comparison of steering methods
van Tuyl et al14 (DAS-steered vs CTX-steered)
 CDAS <1.6 (remission) 57%, 76% and 90% after 8, 21 and 40 weeks in both targeted armsNS
 FNA
 RNA
Edmonds et al15 (SJC-steered vs CRP-steered vs routine care)
 CCRP, SJCNA
 FNA
 RSHS progression CRP group that met CRP target vs patients who did not meet CRP target: 0.53±1.57 vs 2.15±4.18p=0.00
Non-comparative trials
Brenol et al31 (baseline vs 14 months)
 CSJC, TJC and VASpt-pain and VASpt-global health assessment baseline vs 12–14 mp<0.05
DAS28 total 12–14 m 4.64±1.57 vs 3.99±1.45p<0.005
DAS28<2.6 12.6% vs 20.4%p<0.001
CDAI<2.8 8.6% vs 14.2%p<0.001
 FHAQ total 12–14 m 1.45±0.86 vs 1.31±0.81p=0.002
 RNA
Proudman et al32
 CCRP median baseline vs 24 months 14 (6–31) vs 4 (3–4)p<0.05
ESR median baseline vs 24 months 39 (24–54) vs 11 (5.5–18.75)p<0.05
DAS28 (primary outcome) mean score baseline vs 24 months 5.3±1.1 vs 2.7±1.4p<0.05
 FHAQ mean baseline vs 24 months 0.9±0.5 vs 0.2±0.3p<0.05
 RSHS modified median (IQR) total score baseline vs 24 m 8 (5 to 15) vs 13 (8–12)p<0.05
Kuper et al33
 CDAS28<2.6 (remission) after 48–52 weeks 51%NA
 FNA
 RNA
Medication trials
RCTs
FIN-RACo16–20 (combination vs monotherapy)
 CRemission (primary outcome, ACR defi nition of remission) 2 years 37% vs 18%p=0.003
DAS28 median at 2 years 2.0 vs 3.1p=0.005
ACR50, ESR, SJC, TJC, VASpt-global healthNS
 FMean change in HAQNS
 RIncrease in Larsen score after 2 years 4 vs 12p=0.002
NEO-RACo21 (combination+IFX vs combination+placebo)
 CRemission (primary outcome) after 2 years 70% vs 53%p=0.08
 FNA
 RSHS=0 after 2 years 54% vs 41%p=0.005
BeSt22–26 (sequential monotherapy; step-up monotherapy; combination therapy+prednisone; combination therapy with IFX)
 CDAS≤2.4 (target) after
 1 year 53%; 64%; 71%; 74%p<0.01 (1 vs 3 and 1 vs 4)
 2 years 75%; 81%; 78%; 82%NS
VASpt-pain change
 After 6 months with baseline −17.4; −25.5; −30.3; −30.2p=0.001 (1 vs 3+4)
 After 2 years −28.2; −27.3; −26.9; −32.6NS
VASpt-global health assessment after 2 years −26.4; −25.6; −23.9; −31.8NS
F
HAQ mean improvement
 After 12 months 0.7; 0.7; 0.9; 0.8p=0.031 (1 vs 3+4)
 After 24 months 0.7; 0.8; 0.9; 0.9NS
R
SHS mean increase after 2 years 2.0; 2.0; 1.0; 1.0 (9.0; 5.2; 2.6; 2.5)p=0.005 (1+2 vs 3+4)
GUEPARD27 (initial MTX vs initial combination MTX with ADA)
 CDAS28 AUC at 1 year 164.6 vs 186.70.049
 FHAQ increase at 1 year−0.51 vs−0.820.26
 RSHS increase 1.8±4.7 vs 1.9±4.0NS
Saunders et al28 (step-up vs parallel)
 CMean difference
 After 1 year SJC, TJC, CRP, ESR, VASpt-pain,−global health assessment, DAS28NS
 After 1 year OR ACR20 0.9 (0.3–1.6); OR ACR50 0.7 (0.3–1.6); OR ACR70 0.6 (0.2–1.5)NS
 After 1 year OR EULAR remission 0.6 (0.3–1.4)NS
 FHAQ mean differenceNS
 RSHS mean differenceNS
Ferraccioli et al29 (MTX adding CsA; CsA adding MTX; SSZ monotherapy)
 CSJC mean (95%CI) increase
 After 18 months –6.3 (−3.1 to−9.5);−5.0 (−2.8 to−7.8);−3.7 (−0.6 to−6.9)p=0.04 (1 vs 3)
 18–36 months−2.2 (−1.3 to−3.2);−3.1 (−1.9 to−4.3);−1.8 (−0.6 to−3.1)NS
TJC mean (95%CI) increase
 After 18 months−5.8 (−2.7 to−8.9);−5.7 (−2.8 to−8.7);−2.2 (0.8 to−5.3)p=0.001 (1 vs 3 and 2 vs 3)
18–36 months−1.7 (−0.5 to−2.9);−4.8 (−3.6 to−6.1);−2.8 (−1.5 to−4.1)p=0.02 (1 vs 2)
CRP mean (95%CI) increase
 After 18 months−23 (−13.5 to−33.3);−9.0 (−6.4 to 11.6);−11.8 (0.4 to−23.9)p=0.001 (1 vs 3)
 18–36 months−1.8 (2.3 to−5.9);−9.0 (−6.4 to−11.6);−0.9 (2.9 to−4.8)p=0.01 (1 vs 2);
p=0.03 (2 vs 3)
VASpt mean (95%CI) increase
 After 18 months−4.2 (−3.7 to−4.7);−4.4 (−1.9 to−7.0);−2.3 (−1.9 to−2.7)p=0.001 (1 vs 3 and 2 vs 3)
 18–36 months−1.3 (−0.9 to−1.7);−0.6−0.4 to−0.9);−0.6 (−0.3 to−0.9)p=0.001 (1 vs 2)
ACR50 (target) after 18 months 90%; 88%; 24%NS
 FNA
 RNA
Non-randomised comparative trials
Verschueren et al30 (step-down vs step-up)
 CDAS28<2.4 percentage after 4 months 63.2% vs 36.4%p=0.049
 After 12 monthsNS
 FHAQ >0.22 increase after 4 monthsp=0.010
 RNA
  • Published data after approximately 2 years. Data are sorted according to intensive treatment compared with less intensive treatment. ACR, American College of Rheumatism; ADA, adalimumab; AUC, area under the curve; BROSG, British Rheumatoid Outcome Study Group; C, clinical outcomes; CAMERA, Computer Assisted Management for Early Rheumatoid Arthritis; CDAI, Crohn's Disease Activity Index; CRP, C-reactive protein; CsA, ciclosporin; CTX, C-terminal cross-linked telopeptide; DAS, Disease Activity Score; DMARD, disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; F, functional outcome; FIN-RACo, Finnish Rheumatoid Arthritis Combination Therapy; GUEPARD, GUérir la PolyArthrite Rhumatoide Débutante (cure early RA); HAQ, Health Assessment Questionnaire; IFX, infl iximab; MTX, methotrexate; PGA, patient global assessment; R, radiographic outcome; RCT, randomised controlled trial; SJC, swollen joint count; SSZ, sulfasalazine; TICORA, TIght COntrol of Rheumatoid Arthritis; TJC, tender joint count; VAS, visual analogue scale.