(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 | ||||||
|---|---|---|---|---|---|---|
| Author | Groups | Treatment decision driving target | Interval of control examinations | N | Outcomes | Randomisation |
| Goekoop-Ruiterman et al7 | Targeted group (T) | DAS≤2.4 | 3 months | 234 | Clinical outcome at 1 year Primary outcome: change damage progression by the total SHS | Yes |
| Routine control group (R) | Treatment changes left to the discretion of the treating doctor | 3 months | 201 | |||
| Soubrier et al (GUEPARD/ESPOIR)8 | GUEPARD—Targeted group (T) | LDA by DAS28ESR<3.2 | 3 months | 65 | Assessed 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 52 | 130 | ||||
| Van Eijk et al (STREAM)9 | Targeted group (T) | DAS(44-joint score)<1.6 | 3 months | 42 | Clinical 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 events | Yes |
| Routine control group (R) | Treatment according to rheumatologist´s preference | 3 months | 40 | |||
| Schipper et al(DREAM)10 | Targeted group (T) | DAS 28<2.6 | Assessment at weeks 0, 8, 12, 20, 24, 36 | 126 | Clinical 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 year | No |
| Routine control group (R) | Treatment at the discretion of the treating rheumatologist | Assessment at weeks 0, 12, 24, 36, 52 | 126 | |||
| Pope et al11 | DAS—targeted group (T) | DAS28<2.6 | Patients could be seen at any time as per judgement of the treating physician. Recommended visits were at 0, 2, 4, 6, 9, 12, 18 months | 100 | Clinical 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 points | Cluster randomised |
| 0-SJC—targeted group (T) | 0-SJC | Patients could be seen at any time as per judgement of the treating physician. Recommended visits were at 0, 2, 4, 6, 9, 12, 18 months | 99 | |||
| Routine control group (R) | Treatment left at the discretion of the treating physician | Patients could be seen at any time as per judgement of the treating physician. Recommended visits were at 0, 6, 12, 18 months | 109 | |||
| Vermeer et al (DREAM)12 | Targeted group (T) | DAS28<2.6 | 0, 8, 12, 20, 24, 36, 52 weeks | 261 | The ICER per patient in remission and ICUR per QALY were calculated over two and 3 years of follow-up | No |
| Routine control group (R) | Treatment left at the discretion of the rheumatologist | 3 Months | 213 | |||
| Panel (B) Supportive evidence for differences of outcomes depending on reaching different endpoints | ||||
|---|---|---|---|---|
| Author | Patients | Target/outcome | Conclusion | Randomisation |
| Targeting cardiovascular risk | ||||
| Crowson et al24 | Review | n.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 al20 | 195 | Strict remission rates at 6, 12 and 24 months as well as the cumulative work disability days up to 5 years in these four subgroups | Using 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 therapy | Yes |
| Smolen et al21 | 834 enrolled—604 eligible for double-blind period | Sustained LDA | Conventional or reduced doses of etanercept with MTX in patients with moderately active RA more effectively maintain LDA than does MTX alone after withdrawal of etanercept | Yes |
| Radner et al19 | 356 | Physical function, health-related quality of life, work productivity, estimation of direct and indirect costs | Patient 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 states | No |
| Education | ||||
| Pope et al25 | 1000 serial RA charts | SDAI | Small group learning with feedback from practice audits is an inexpensive way to improve outcomes in RA | Cluster randomised |
| Additional evidence | ||||
| Thiele et al28 | 6864 | DAS28 (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 account | No |
| Vermeer et al29 | 409 | DAS28, HAQ, SF36, MCS, SHS | In 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 practice | No |
| Sakellariou et al30 | 166 | SDAI, DAS28, HAQ, PDPS | The new remission definitions confirmed their validity in an observational setting and identify patients with better disease control. | No |
| Balsa et al31 | 97 | SDAI | The 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 US | No |
| Dale et al32 | 111 | DAS44, HAQ, MRI (RAMRIS), X-ray hands + feet | MSUS 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 al33 | 53 | DAS28 | Compared 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 synovitis | No |
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.