Table 3

Outcome of steering and drug strategy trials

Steering trials
RCTs
TICORA5 (DAS-steered vs routine care)
C	EULAR 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
F	NA
R	Median (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)
C	Number 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=0.001	p<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
F	HAQ-AUC	NS
R	Annual radiographic progression	NS
	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)*
C	DAS₂₈≤3.2 at 24 weeks: 31% vs 16% (primary outcome)	p<0.028
	DMARD changes: 20% vs 9% (primary outcome)	p<0.05
F	NA
R	NA
BROSG8 9 (intensive care vs symptomatic care)
C	SJC, TJC, ESR and PGA	NS
F	HAQ (primary outcome): sign deterioration in both arms: NS between treatment arms	NS
R	Larsen score	NS
*van Hulst et al10 (DAS-guided vs routine care)*
C	DAS₂₈ mean change after 18 months 0.5 vs 0.65	NS
F	NA
R	NA

Non-randomised comparative trials
*Allaart et al11 (DAS-steered vs routine treatment)*
C	ESR 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±1.5	p=0.001
F	HAQ mean change after 1 year −0.7±−0.7 vs −0.5±−0.7	p=0.029
R	NA
*Stenger et al12 (CRP-steered high-risk/low-risk vs routine care high-risk/low-risk)*
C	AUC for CRP (target) lower in intensive group after 2 years
	High-risk patients	p=0.002
	Low-risk patients	p=0.20
F	NA
R	SHS 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)*
C	DAS<1.6 (remission) after 5 years 9% vs 11%	NS
F	NA
R	NA

RCTs comparison of steering methods
*van Tuyl et al14 (DAS-steered vs CTX-steered)*
C	DAS <1.6 (remission) 57%, 76% and 90% after 8, 21 and 40 weeks in both targeted arms	NS
F	NA
R	NA
*Edmonds et al15 (SJC-steered vs CRP-steered vs routine care)*
C	CRP, SJC	NA
F	NA
R	SHS progression CRP group that met CRP target vs patients who did not meet CRP target: 0.53±1.57 vs 2.15±4.18	p=0.00

Non-comparative trials
*Brenol et al31 (baseline vs 14 months)*
C	SJC, TJC and VAS_pt-pain and VAS_pt-global health assessment baseline vs 12–14 m	p<0.05
	DAS₂₈ total 12–14 m 4.64±1.57 vs 3.99±1.45	p<0.005
	DAS₂₈<2.6 12.6% vs 20.4%	p<0.001
	CDAI<2.8 8.6% vs 14.2%	p<0.001
F	HAQ total 12–14 m 1.45±0.86 vs 1.31±0.81	p=0.002
R	NA
*Proudman et al32*
C	CRP 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±1.4	p<0.05
F	HAQ mean baseline vs 24 months 0.9±0.5 vs 0.2±0.3	p<0.05
R	SHS modified median (IQR) total score baseline vs 24 m 8 (5 to 15) vs 13 (8–12)	p<0.05
*Kuper et al33*
C	DAS₂₈<2.6 (remission) after 48–52 weeks 51%	NA
F	NA
R	NA

Medication trials
RCTs
FIN-RACo16–20 (combination vs monotherapy)
C	Remission (primary outcome, ACR defi nition of remission) 2 years 37% vs 18%	p=0.003
	DAS₂₈ median at 2 years 2.0 vs 3.1	p=0.005
	ACR₅₀, ESR, SJC, TJC, VAS_pt-global health	NS
F	Mean change in HAQ	NS
R	Increase in Larsen score after 2 years 4 vs 12	p=0.002
NEO-RACo21 (combination+IFX vs combination+placebo)
C	Remission (primary outcome) after 2 years 70% vs 53%	p=0.08
F	NA
R	SHS=0 after 2 years 54% vs 41%	p=0.005
BeSt22–26 (sequential monotherapy; step-up monotherapy; combination therapy+prednisone; combination therapy with IFX)
C	DAS≤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
	VAS_pt-pain change
	After 6 months with baseline −17.4; −25.5; −30.3; −30.2	p=0.001 (1 vs 3+4)
	After 2 years −28.2; −27.3; −26.9; −32.6	NS
	VAS_pt-global health assessment after 2 years −26.4; −25.6; −23.9; −31.8	NS
F
	HAQ mean improvement
	After 12 months 0.7; 0.7; 0.9; 0.8	p=0.031 (1 vs 3+4)
	After 24 months 0.7; 0.8; 0.9; 0.9	NS
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)
C	DAS₂₈ AUC at 1 year 164.6 vs 186.7	0.049
F	HAQ increase at 1 year−0.51 vs−0.82	0.26
R	SHS increase 1.8±4.7 vs 1.9±4.0	NS
*Saunders et al28 (step-up vs parallel)*
C	Mean difference
	After 1 year SJC, TJC, CRP, ESR, VAS_pt-pain,−global health assessment, DAS₂₈	NS
	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
F	HAQ mean difference	NS
R	SHS mean difference	NS
*Ferraccioli et al29 (MTX adding CsA; CsA adding MTX; SSZ monotherapy)*
C	SJC 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)
	VAS_pt 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
F	NA
R	NA

Non-randomised comparative trials
*Verschueren et al30 (step-down vs step-up)*
C	DAS₂₈<2.4 percentage after 4 months 63.2% vs 36.4%	p=0.049
	After 12 months	NS
F	HAQ >0.22 increase after 4 months	p=0.010
R	NA

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.