Table 2

Biological DMARD strategies studies without a treat-to-target approach—study outcomes

Patient groupBiological DMARDStudy (n=total number enrolled)OutcomeResult
DMARD-naiveABTEmery 2010 (ADJUST)56 (n=56)Primary EP:Groups: ABT vs placebo
Year 1: development of RA (ACR criteria)1/26 (46%) vs 16/24 (67%)
ETNMoreland 2012 (TEAR)*18 (n=755)Primary EP:(completers only analysis)
DAS28-ESR from week 48 to week 102No difference between groups (p=0.28)
Other:
DAS28 ESR week 24IE+IT vs SE+ST p<0.0001
DAS28 ESR remission (%) week 102IE/IT/SE/ST†: 56.5/ 59.1/ 52.9/ 56.5, p=0.93
ACR responses (%) at week 102ACR20 and ACR 50, p=NS between groups
ACR70: IE+SE vs IT+ST 18.25 vs 11.3%, p=0.01
Radiographic non-progression (%) at week 102IE/IT/SE/ST 79.4/64.9/71.1/68.3, p=0.33
IE+SE vs IT+ST 76.8 vs 66.4, p=0.02
IFXvan Vollenhoven 2009/ 2012 (SWEFOT)16 60
(n=487)
Primary EP:Groups: MTX+SSZ+HCQ vs MTX+IFX‡
EULAR good response at 12 months25% vs 39%, (RR 1.59 [95% CI 1.1 to 2.3]), p=0.016
Other:
EULAR good response at 24 months31% vs 38%, p=0.204
Mean radiographic progression (SD) at 2 years7.23 (12.72) vs 4 (10.05), p=0.009
MTX naiveADAKavanaugh 201322 Fleischmann ACR 2012 (OPTIMA)61
(n=1032)
Primary EP:Groups: ADA+MTX vs Placebo+MTX§
Composite DAS28(CRP)<3.2 at week 78 and no radiographic progression from baseline to week 78 (mTSS ≤ 0.5)
Other:
Period 1: Stable LDA at weeks 22 and 2644% vs 24% (p<0.001)
Period 2:
Week 78 DAS28CRP<3.2; ΔmTSS ≤0.5; DAS28CRP<3.2 and ΔmTSS≤0.565% vs 65%; 86% vs 72% (p<0.001), 60% vs 48% (p<0.001)
ETNEmery 2009 (COMET)50 (n=274)2 year EP include:Groups: EM/EM, ME/E, M/EM, M/M¶
Remission (DAS28<2.6):62/108, 54/108, 51/88 and 33/94 (p<0.01 for EM/EM and M/EM vs M/M)
Radiographic non-progression (mTSS≤0.5):89/99, 74/99, 59/79 and 56/83 (p<0.01 EM/EM vs other groups)
MTX IRETNO'Dell 2013 (RACAT)19 (n=353)Primary EP:Groups: MTX+SSZ+HCQ vs ETN+MTX (completers only analysis)
Mean (SD) ΔDAS28 at week 48**−2.12 (1.28) vs -2.29 (1.30) (p=0.26)
Other:
Week 24: Mean (SD) ΔDAS28−1.79 (1.20) vs −2.06 (1.35) (p=0.06)
Mean (SD) ΔmTSS0.42(1.91) vs 0.003 (3.62) (p=0.20)
Week 48: Mean (SD) ΔmTSS0.54 (1.93) vs 0.29(3.32) (p=0.43)
  • *80% DMARD-naive.

  • †TEAR comparator groups: IE, immediate treatment with ETN+MTX; IT, immediate treatment with triple therapy; SE: step-up treatment from MTX monotherapy to ETN+MTX if DAS28 ESR ≥3.2 at week 24; ST: step-up treatment from MTX monotherapy to triple therapy (MTX+SSZ+HCQ) if DAS28 ESR ≥3.2 at week 24.

  • ‡SWEFOT comparator groups: MTX monotherapy then randomisation to group (A) (MTX+SSZ+HCQ) or (B) (MTX+IFX) if not in LDA after 3–4 months.

  • §OPTIMA comparator groups: Period 1: ADA+MTX vs Placebo+MTX for 26 weeks: Period 2: Patients assessed for LDA (DAS28 (CRP)<3.2) at weeks 22 and 26 and categorised as responders or incomplete responders: In the ADA+MTX, responders may have been randomised to ADA withdrawal; in the Placebo+MTX arm, incomplete responders may have been randomised to starting ADA.

  • ¶COMET: Randomisation at baseline for 2-year period to MTX monotherapy for 1 year then continue or add ETN or MTX+ETN for 1 year then continue or stop MTX. (‘denotes treatment in the first year’/‘denotes treatment in the second year’). E=etanercept; M=methotrexate.

  • **Original proposed primary endpoint=difference in proportion of participants with DAS28 ≤3.2 at week 48; changed due to unexpected low enrolment.

  • ABT, abatacept; ADA, adalimumab; DMARD, disease modifying antirheumatic drug; ETN, etanercept; HCQ, hydroxychloroquine; IFX, infliximab; LDA, low disease activity; MTX, methotrexate; NS, non-significant; Primary EP, primary endpoint; SD, standard deviation; SSZ, sulphasalazine; TT, triple therapy.