Table 1

Targets and visit intervals (left columns) and clinical, functional and structural outcomes (right columns) of core trials

Group	Treatment-decision driving target	Interval of controls	N	Outcomes/final treatment target p Values indicate differences of outcomes between the targeted (T) and the routine group (R)
(A) TICORA26
Targeted group (T)	DAS<2.4 LDA	1 Month	55	Clinicaloutcome at 18 months EULAR good response (primary outcome): OR^* 5.8 (2.4 to 13.9); 82% targeted (T) versus 44% routine (R); p<0.0001 EULAR remission: OR^* 9.7 (3.9 to 23.9), 64% T versus 16% R; p<0.0001 ACR70: OR^* 11 (4.5 to 27), 71% T versus 18% R; p<0.0001 Functional outcome at 18 months HAQ change: −0.97±0.8 T versus −0.47±0.9 R; p=0.0025 Radiographic outcome at 18 months; median (IQR) Progression of erosion score: 0.5 (0–3.357) T versus 3 (0.5–8.5) R; p=0.002 Change in TSS: 4.5 (1–9.875) T versus 8.5 (2.0–15.5) R; p=0.02 Change in JSN: 3.25 (1.125–7.5) T versus 4.5 (1.5–9.0) R; p=0.331
Routine control group (R)	Opinion of treating rheumatologist	1 Month	55
(B) CAMERA27
Targeted group (T)	Improvement of number of swollen joints: >20% compared to previous visit/50% compared to baseline Improvement in 2 out of 3 criteria: ESR, TJC, PGA >20% compared to previous visit	1 Month	151	Clinicaloutcome at 1 year^† and at 2 years^‡ Number of patients in remission for 3 months (primary outcome): 35% T versus 14% R; p<0.001^† 50% T versus 37% R; p<0.029^‡ Mean (95% CI) time until remission (months): 10.4 (9.1 to 11.7) T versus 14.3 (12.6 to 16.1) R; p<0.001 Duration (months) of all periods of remission: 11.6 (10.1–13.1) T versus 9.1 (7.6–10.6) R; p=0.025 ACR50: 58% T versus 43% R; p<0.01^† 46% T versus 45% R; p=NS^‡ Functional outcome at 1 year^† and at 2 years^‡ HAQ mean±SD-change: −0.44±0.59 T versus −0.39±0.66 R; p=NS^†; −0.41±0.64 T versus −0.42±0.76 R; p=NS^‡ Radiographic outcome at 2 years Annual radiographic progression: median (IQR) change (units/year): 0 (0–2.0) T versus 0 (0–2.5) R; p=0.9
Routine control group (R)	Decrease of SJC, if number of SJ unchanged, assessors' judgement, looking at TJC, ESR, PGA	3 Months	148
(C) Fransen et al28
Targeted group (T)	DAS28<3.2 LDA	1 Month starting, then 2 months, then 3 months (both groups)	205	Clinicaloutcome at 24 weeks Patients in DAS28/LDA: 31% T versus 16% R; p=0.028 Mean±SD changes in DAS28: −0.4±1.0 T versus −0.14±1.2 R; p=0.36 DMARD changes: 20% T versus 9% R; p=0.013 Functional data: NR (NS) Radiographic: NR
Routine control group (R)	Opinion of treating rheumatologist		179
(D) Symmons et al29
Targeted group (T)	CRP<twice the upper limit of normal range TJC=0 and SJC=0 Symptom control	At least every 4 months (both groups)	233	Clinicaloutcome at 3 years: (adjusted mean difference (95% CI)) EGA: 3.76 (0.03–7.52); p=0.045 OSRA: 0.41 (0.01–0.71); p=0.010 SJC, TJC, ESR and PGA: p=NS Functional outcome at 3 years: HAQ (primary outcome): sign deterioration in both arms; mean difference between T and R: p=0.82 Radiographic outcome at 3 years: Total Larsen score: deterioration in both arms of (significant in routine group (p=0.035) but not in the targeted group (p=0.093); difference T versus R: p=NS Eroded joint count: increased slightly in both treatment arms, difference T versus R: p=NS
Routine control group (R)	Symptom control	At least every 4 months (both groups)	233
(E) Edmonds et al31 (abstract)
Targeted group I	CRP normal range	1 Month (both groups)	82	Clinicaloutcome at 2 years: Target ‘SJC<3’ was met in 29%, target ‘normal CRP’ in 41% of visits (p: NA) Functional outcomes: NR Radiographic outcomes at 2 years Radiographic progression scores NS between study arms but: erosion progression 0.2±1.0 versus 1.0±2.5 (p<0.03), JSN 0.3±1.3 versus 1.2±2.6 (p<0.03), total score 0.5±1.6 versus 2.2±4.2 (p<0.005) if AUC-CRP target achieved, as compared to not achieved (not the case for SJC-target) (p NA).
Targeted group II	SJC <3		85
Routine control group	–		82
(F) van Tuyl et al30
Targeted group I	DAS28<3.2 LDA	8 Weeks, then 13 weeks (both groups)	11	Clinicaloutcomes at 40 weeks Remission rates: in both targeted arms: 90% (after 8 and 21 weeks: 57% and 76%) ACR20/50/70/90: 100%/95%/71%/43% Functional outcomes: NR Radiographic outcomes: NR
Targeted group II	Cartilage degradation: CTX-II excretion ≤150 nmol/mmol creatinine	8 Weeks, then 13 weeks (both groups)	10
(G) Stenger et al32
Targeted group (T)	CRP decrease >50%	8 Weeks (both groups)	139	Clinicaloutcomes at 1 year^† and at 2 years^‡ AUC-CRP (mg (week/l; median (range)): 1136 (144–3563) T versus 1836 (26–8051) R; p=0.02^†; 1963 (212–8515) T versus 3025 (46–15632) R; p=0.002^‡ Functional outcomes: NR Radiographic outcomes at 1 year^† and at 2 years^‡ Median (range) progression rate: 17.0 (0–74) T versus 17.5 (0–130) R; p=0.22^† 26.0 (0–100) T versus 35 (1–188) R; p=0.03^‡
Routine control group (R)	Opinion of treating rheumatologist	8 Weeks (both groups)	89

↵* OR (95% CI);
↵† outcome at 1 year;
↵‡ outcome at 2 years.
AUC, area under the curve; ACR, American College of Rheumatology; CAMERA, Computer Assisted Management in Early Rheumatoid Arthritis; CRP, C reactive protein; CTX-II, C-terminal cross-linking of type II collagen; DAS, Disease Activity Score; DMARD, disease-modifying antirheumatic drugs; EGA, evaluator global assessment; ESR, erythrocyte sedimentation rate; EULAR, European League Against Rheumatism; HAQ, Health Assessment Questionnaire; JSN, joint space narrowing; LDA, low disease activity; NR, not reported; OSRA, overall status in rheumatoid arthritis; PGA, physician's global assessment; SJC, swollen joint count; TICORA, tight control of rheumatoid arthritis; TJC, total joint count; TSS, total Sharp score.