Table 5

Treat-to-target strategy trials comparing ab initio versus delayed intensive therapy in terms of efficacy in patients with early arthritis

Study (LoE)TrialnInitial armsType of intensificationStep-up fromTwelve-month remissionRadiographic outcome after step-downRisk of bias
Nam J et al (1b)48IDEA55IFX+MTXIFX dose increaseWeek 26DAS44 <1.648%ΔmTSS at week 501.2Low
57MTX+MP+PBOcsDMARD combination36%2.8
Ter Wee et al (1b)49COBRA-light81MTX+SSZ+GCMTX dose increase, then ETN.Week 26DAS44 <1.647%ΔmTSS at week 520.5±1.6High†
81MTX +GCETN38%0.6±1.4
Axelsen et al (1b)50 Hørslev-Petersen et al51OPERA89ADA+MTXcsDMARD combination or bDMARDWeek 12DAS28CRP <2.674%mTSS at week 525.0±5.2Low
91PBO+MTXcsDMARD combination, then ADA49%***5.5±6.2
De Jong et al (1b)17tREACH91csDMARD combination+Intramuscular-GCMTX+ETN, then MTX+ADAWeek 12DAS <1.661%ΔmTSS at week 520.1 (0.0–1.0)High‡
93csDMARD combination+oral GCMTX+ETN, then MTX+ADA54%0.0 (0.0–1.0)
97MTX+ oral GCMTX+ETN, then MTX+ADA51%0.0 (0.0–1.0)
Atsumi et al (2c)44C-OPERA159CZP+MTXopen label CZP+MTXWeek 24DAS28 <2.657%ΔmTSS at week 520.4±2.7Low
Bijlsma et al (1b)42 52U-ACT-EARLY STRATEGY STUDY106TCZ+MTXTCZ+MTX+HCQ, then TNFi+MTXDAS28 <2.6 with SJC ≤4, for ≥24 weeks$86%ΔmTSS at week 520.5±1.5Low
103TCZ+PBOTCZ+HCQ, then TCZ+MTX88%0.8±3.2
108MTX+PBOMTX+HCQ, then MTX+TCZ77%1.0±2.9*
  • Results are expressed in %; means±SD or medians (IQR).

  • Comparison of ab initio versus delayed intensive therapy *p<0.05; ***p<0.001.

  • †Open label trial.

  • ‡Single-blinded trial.

  • ADA, adalimumab; bDMARD, biological DMARD; csDMARD, conventional synthetic disease modifying antirheumatic drug; DAS, Disease Activity Score; ETN, etanercept; HCQ, hydroxychloroquine; IFX, infliximab; LoE, level of evidence; MP, methylprednisolone; MTX, methotrexate; mTSS, variation of modified total Sharp score; TCZ, tocilizumab; TNFi, tumour necrosis factor inhibitors.