Study (LoE) | Trial | n | Initial arms | Type of intensification | Step-up from | Twelve-month remission | Radiographic outcome after step-down | Risk of bias | ||
---|---|---|---|---|---|---|---|---|---|---|
Nam J et al (1b)48 | IDEA | 55 | IFX+MTX | IFX dose increase | Week 26 | DAS44 <1.6 | 48% | ΔmTSS at week 50 | 1.2 | Low |
57 | MTX+MP+PBO | csDMARD combination | 36% | 2.8 | ||||||
Ter Wee et al (1b)49 | COBRA-light | 81 | MTX+SSZ+GC | MTX dose increase, then ETN. | Week 26 | DAS44 <1.6 | 47% | ΔmTSS at week 52 | 0.5±1.6 | High† |
81 | MTX +GC | ETN | 38% | 0.6±1.4 | ||||||
Axelsen et al (1b)50 Hørslev-Petersen et al51 | OPERA | 89 | ADA+MTX | csDMARD combination or bDMARD | Week 12 | DAS28CRP <2.6 | 74% | mTSS at week 52 | 5.0±5.2 | Low |
91 | PBO+MTX | csDMARD combination, then ADA | 49%*** | 5.5±6.2 | ||||||
De Jong et al (1b)17 | tREACH | 91 | csDMARD combination+Intramuscular-GC | MTX+ETN, then MTX+ADA | Week 12 | DAS <1.6 | 61% | ΔmTSS at week 52 | 0.1 (0.0–1.0) | High‡ |
93 | csDMARD combination+oral GC | MTX+ETN, then MTX+ADA | 54% | 0.0 (0.0–1.0) | ||||||
97 | MTX+ oral GC | MTX+ETN, then MTX+ADA | 51% | 0.0 (0.0–1.0) | ||||||
Atsumi et al (2c)44 | C-OPERA | 159 | CZP+MTX | open label CZP+MTX | Week 24 | DAS28 <2.6 | 57% | ΔmTSS at week 52 | 0.4±2.7 | Low |
157 | PBO+MTX | CZP+MTX | 37%*** | 1.6±4.9 | ||||||
Bijlsma et al (1b)42 52 | U-ACT-EARLY STRATEGY STUDY | 106 | TCZ+MTX | TCZ+MTX+HCQ, then TNFi+MTX | DAS28 <2.6 with SJC ≤4, for ≥24 weeks$ | 86% | ΔmTSS at week 52 | 0.5±1.5 | Low | |
103 | TCZ+PBO | TCZ+HCQ, then TCZ+MTX | 88% | 0.8±3.2 | ||||||
108 | MTX+PBO | MTX+HCQ, then MTX+TCZ | 77% | 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.