Table 1

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

GroupTreatment-decision driving targetInterval of controlsNOutcomes/final treatment target p Values indicate differences of outcomes between the targeted (T) and the routine group (R)
Targeted group (T)DAS<2.4 LDA1 Month55
  • 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 rheumatologist1 Month55
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 visit1 Month151
  • 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, PGA3 Months148
(C) Fransen et al28
Targeted group (T)DAS28<3.2 LDA1 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 rheumatologist179
(D) Symmons et al29
Targeted group (T)CRP<twice the upper limit of normal range TJC=0 and SJC=0 Symptom controlAt 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 control233
(E) Edmonds et al31 (abstract)
Targeted group ICRP normal range1 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 IISJC <385
Routine control group82
(F) van Tuyl et al30
Targeted group IDAS28<3.2 LDA8 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 IICartilage degradation: CTX-II excretion ≤150 nmol/mmol creatinine10
(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 rheumatologist89
  • * 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.