Table 1

 (A) Publications comparing an a priori targeted treatment strategy with routine care; (B) supportive evidence

(A) Studies directly addressing outcomes based on different treatment strategies
AuthorGroupsTreatment decision driving targetInterval of control examinationsNOutcomesRandomisation
Goekoop-Ruiterman et al7Targeted group (T)DAS≤2.43 months234Clinical outcome at 1 year Primary outcome: change damage progression by the total SHSYes
Routine control group (R)Treatment changes left to the discretion of the treating doctor3 months201
Soubrier et al (GUEPARD/ESPOIR)8GUEPARD—Targeted group (T)LDA by DAS28ESR<3.23 months65Assessed variables: SJ, TJ, VAS pain, VAS general wellbeing, VAS physician overall assessment, morning stiffness, ESR, CRP, HAQ, radiographs hands and feet (SHS)No
ESPOIR—Routine control group (R)Assessment at weeks 0, 24 and 52130
Van Eijk et al (STREAM)9Targeted group (T)DAS(44-joint score)<1.63 months42Clinical outcome at 2 years Primary endpoint: progression of radiographic joint damage at 2 years Secondary endpoints: difference between the two treatment strategies after 2 years regarding DAS, the percentage of patients in clinical remission (DAS<1.6), HAQ and adverse eventsYes
Routine control group (R)Treatment according to rheumatologist's preference3 months40
Schipper et al(DREAM)10Targeted group (T)DAS 28<2.6Assessment at weeks 0, 8, 12, 20, 24, 36126Clinical outcome at 1 year Primary endpoint: percentage of patients in remission (DAS28<2.6) Secondary endpoint: time to achieve remission, the course over time of the DAS28, the percentage of patients with “low” disease activity (DAS28≤3.2), the mean change in DAS28 and individual core set variables from baseline to 1 yearNo
Routine control group (R)Treatment at the discretion of the treating rheumatologistAssessment at weeks 0, 12, 24, 36, 52126
Pope et al11DAS—targeted group (T)DAS28<2.6Patients could be seen at any time as per judgement of the treating physician. Recommended visits were at 0, 2, 4, 6, 9, 12, 18 months100Clinical outcome at 1 year Primary endpoint: change in DAS 28 Secondary endpoint: changes at 6, 12, and 18 months in the SJC, TJC, CRP, ESR, HAQ, PGL, WLQ, patient satisfaction (5-point Likert scale), achievement of LDA (DAS<3.2), disease remission (DAS<2.6), and good/moderate EULAR response and time to achieve these end pointsCluster randomised
0-SJC—targeted group (T)0-SJCPatients could be seen at any time as per judgement of the treating physician. Recommended visits were at 0, 2, 4, 6, 9, 12, 18 months99
Routine control group (R)Treatment left at the discretion of the treating physicianPatients could be seen at any time as per judgement of the treating physician. Recommended visits were at 0, 6, 12, 18 months109
Vermeer et al (DREAM)12Targeted group (T)DAS28<2.60, 8, 12, 20, 24, 36, 52 weeks261The ICER per patient in remission and ICUR per QALY were calculated over two and 3 years of follow-upNo
Routine control group (R)Treatment left at the discretion of the rheumatologist3 Months213
Panel (B) Supportive evidence for differences of outcomes depending on reaching different endpoints
AuthorPatientsTarget/outcomeConclusionRandomisation
Targeting cardiovascular risk
Crowson et al24Reviewn.a.Suppression inflammation—may also reduce risk of heart disease; investigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease and help identify novel therapeutic targets for the prevention and treatment of heart disease
Therapies used to treat RA may also affect the development of heart diseases, by suppressing inflammation, they may also reduce the risk of heart disease. Therapies used to treat RA may also affect the development of heart diseases, by suppressing inflammation, they may also reduce the risk of heart disease
Review
Work/productivity
Rantalaiho et al20195Strict remission rates at 6, 12 and 24 months as well as the cumulative work disability days up to 5 years in these four subgroupsUsing targeted treatment with monotherapy may well substitute for using combination DMARDs, but to benefit as many early RA patients as possible both approaches are necessary. Targeted treatment strategy is beneficial irrespective of the type of therapyYes
Smolen et al21834 enrolled—604 eligible for double-blind periodSustained LDAConventional or reduced doses of etanercept with MTX in patients with moderately active RA more effectively maintain LDA than does MTX alone after withdrawal of etanerceptYes
Radner et al19356Physical function, health-related quality of life, work productivity, estimation of direct and indirect costsPatient with remission show better function, health-related quality and productivity, even when compared with another good state, such as LDA. Also from a cost perspective, remission appears superior to all other statesNo
Education
 Pope et al251000 serial RA chartsSDAISmall group learning with feedback from practice audits is an inexpensive way to improve outcomes in RACluster randomised
Additional evidence
 Thiele et al286864DAS28 (Boolean/SDAI)Patients fulfilling the new remission criteria tend to be not only free from active RA, but also from other disabling diseases. If these criteria are applied in clinical practice to guide treatment decisions, the impact of comorbidity should be taken into accountNo
 Vermeer et al29409DAS28, HAQ, SF36, MCS, SHSIn very early RA, T2T leads to high (sustained) remission rates, improved physical function and health-related quality of life, and limited radiographic damage after 3 years in daily clinical practiceNo
 Sakellariou et al30166SDAI, DAS28, HAQ, PDPSThe new remission definitions confirmed their validity in an observational setting and identify patients with better disease control.No
 Balsa et al3197SDAIThe results suggest that the SDAI classification of remission is closer to the concept of an absence of inflammatory activity, as defined by the absence of positive PD signal by USNo
 Dale et al32111DAS44, HAQ, MRI (RAMRIS), X-ray hands + feetMSUS disease activity assessment was not associated with improved clinical outcomes except a higher rate of DAS44 remission after 18 months.
Target US sonographic remission does not appear to be superior to clinical LDA
Yes
 Dale et al3353DAS28Compared to the DAS28, global RA disease activity assessment using a limited MSUS joint set provided additional disease activity information and led to altered treatment decisions in a significant minority of occasions. This may allow further tailoring of DMARD therapy by supporting DMARD escalation in patients with continuing subclinical synovitis and preventing escalation in symptomatic patients with minimal clinical and/or ultrasonographic synovitisNo
  • CRP, C reactive protein; DAS, disease activity score; DMARD, disease-modifying antirheumatic drug; DREAM, Dutch Rheumatoid Arthritis Monitoring; ESPOIR, Etude et Suivi des Polyarthrites Indifférenciées Récentes; ESR, erythrocyte sedimentation rate; GUEPARD, Guérir la Polyarthrite Rhumatoide Débutante; HAQ, health assessment questionnaire; ICER, incremental cost-effectiveness ratio; ICUR, incremental cost utility ratio; LDA, low-disease activity; MCS, mental component summary; MSUS, musculoskeletal ultrasound; MTX, methotrexate; PDPS, power Doppler-positive synovitis; PD, power Doppler; PGL, patient global assessment of disease activity; QALY, quality-adjusted life-year; RA, rheumatoid arthritis; RAMRIS, rheumatoid arthritis MRI joint space narrowing score; SDAI, simplified disease activity index; SF36, short form 36 physical component summary; SHS, Sharp/van der Heijde radiographic score; SJ, swollen joint; SJC, swollen joint count; STREAM, Strategies in Early Arthritis Management TJ, tender joint; TJC, tender joint count; T2T, treat to target; US, ultrasound; VAS, visual analogue scale; WLQ, work limitations questionnaire.