Biological DMARD strategies studies without a treat-to-target approach—study outcomes
| Patient group | Biological DMARD | Study (n=total number enrolled) | Outcome | Result |
|---|---|---|---|---|
| DMARD-naive | ABT | Emery 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%) | |||
| ETN | Moreland 2012 (TEAR)*18 (n=755) | Primary EP: | (completers only analysis) | |
| DAS28-ESR from week 48 to week 102 | No difference between groups (p=0.28) | |||
| Other: | ||||
| DAS28 ESR week 24 | IE+IT vs SE+ST p<0.0001 | |||
| DAS28 ESR remission (%) week 102 | IE/IT/SE/ST†: 56.5/ 59.1/ 52.9/ 56.5, p=0.93 | |||
| ACR responses (%) at week 102 | ACR20 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 102 | IE/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 | ||||
| IFX | van Vollenhoven 2009/ 2012 (SWEFOT)16 60 (n=487) | Primary EP: | Groups: MTX+SSZ+HCQ vs MTX+IFX‡ | |
| EULAR good response at 12 months | 25% vs 39%, (RR 1.59 [95% CI 1.1 to 2.3]), p=0.016 | |||
| Other: | ||||
| EULAR good response at 24 months | 31% vs 38%, p=0.204 | |||
| Mean radiographic progression (SD) at 2 years | 7.23 (12.72) vs 4 (10.05), p=0.009 | |||
| MTX naive | ADA | Kavanaugh 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 26 | 44% vs 24% (p<0.001) | |||
| Period 2: | ||||
| Week 78 DAS28CRP<3.2; ΔmTSS ≤0.5; DAS28CRP<3.2 and ΔmTSS≤0.5 | 65% vs 65%; 86% vs 72% (p<0.001), 60% vs 48% (p<0.001) | |||
| ETN | Emery 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 IR | ETN | O'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) ΔmTSS | 0.42(1.91) vs 0.003 (3.62) (p=0.20) | |||
| Week 48: Mean (SD) ΔmTSS | 0.54 (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.