Combined results from analyses of multiply imputed datasets of primary and secondary efficacy outcomes at weeks 52 and 78
| Outcome | MTX+PBO n=55 | MTX+ETN n=55 | Unadjusted (95% CI) | Adjusted (95% CI) | p |
|---|---|---|---|---|---|
| Week 52 | |||||
| NTSJ | 28.1% | 32.5% | OR 1.23 (0.54 to 2.84) | OR 1.32 (0.56 to 3.09)* | 0.522 |
| ACR 2010 remission (Boolean) | 22.5% | 26.7% | OR 1.26 (0.50 to 3.13) | OR 1.24 (0.49 to 3.12)* | 0.653 |
| ACR 2010 remission (SDAI≤3.3) | 37.0% | 47.5% | OR 1.54 (0.69 to 3.41) | OR 1.57 (0.68 to 3.61) | 0.287 |
| DAS44-CRP | −1.32 | −1.45 | −0.13 (−0.56 to 0.30) | −0.11 (−0.47 to 0.26) | 0.554 |
| Pain VAS† | −12.0 (−36.8 to −0.6) | −30.4 (−54.3 to −1.8) | −18.4 (−35.2 to −1.6)‡ | −7.9 (−20.7 to 4.9)‡ | 0.222 |
| Fatigue VAS† | −16.2 (−35.1 to 9.9) | −21.4 (−41.8 to −0.4) | −5.2 (−21.6 to 11.2)‡ | −8.5 (−27.0 to 10.0)‡ | 0.363 |
| Physician VAS† | −23.2 (−32.2 to −13.4) | −27.6 (−36.8 to −16.8) | −4.4 (−11.8 to 3.0)‡ | −2.4 (−6.2 to 1.4)‡ | 0.203 |
| EMS† | −50.0 (−79.8 to −14.8) | −48.0 (−116.6 to −15.7) | 2.0 (−27.5 to 31.5)‡ | −6.7 (−15.3 to 1.90)‡ | 0.126 |
| HAQ-DI | −0.31 | −0.40 | −0.10 (−0.30 to 0.11) | −0.09 (−0.29 to 0.11) | 0.381 |
| SF-36 MCS | 2.99 | 0.97 | −2.02 (−7.09 to 3.05) | 0.29 (−4.05 to 4.64) | 0.893 |
| SF-36 PCS | 6.93 | 8.10 | 1.16 (−3.36 to 5.68) | 2.17 (−4.17 to 4.60) | 0.922 |
| EQ-5D-3L† | 0.113 (0.000 to 0.245) | 0.128 (−0.024 to 0.250) | 0.016 (−0.11 to 0.14)‡ | 0.052 (−0.063 to 0.166)*‡ | 0.373 |
| ERO | 0.37 | 0.23 | −0.14 (−0.47 to 0.19) | −0.13 (−0.44 to 0.18) | 0.408 |
| JSN | 0.54 | 0.68 | 0.14 (−0.36 to 0.64) | 0.25 (−0.24 to 0.74) | 0.308 |
| mTSS | 0.91 | 0.90 | 0.00 (−0.64 to 0.63) | 0.12 (−0.47 to 0.72) | 0.676 |
| ERO† | 0.00 (0.00 to 0.52) | 0.00 (0.00 to 0.47) | −0.00 (−0.15 to 0.15)‡ | 0.00 (−0.15 to 0.15)*‡ | 1.000 |
| JSN† | 0.13 (0.00 to 1.13) | 0.41 (0.00 to 0.96) | 0.29 (−0.23 to 0.80)‡ | 0.22 (−0.22 to 0.66)‡ | 0.327 |
| mTSS† | 0.50 (0.00 to 1.66) | 0.52 (0.00 to 1.16) | 0.02 (−0.46 to 0.51)‡ | 0.08 (−0.52 to 0.68)‡ | 0.791 |
| Progression ≤0.5 | 54.4% | 48.0% | OR 0.77 (0.32 to 1.87) | OR 0.71 (0.29 to 1.76)* | 0.462 |
| Progression ≤SDC | 95.5% | 93.1% | OR 0.67 (0.09 to 4.84) | OR 0.40 (0.04 to 3.75)* | 0.423 |
| US GS>1PD>0 | 35.7% to n=46 | 27.5% to n=48 | OR 0.68 (0.28 to 1.68) | OR 0.63 (0.23 to 1.72) | 0.372 |
| US total GS score† | −1.0 (−6.4 to 5.0) | −3.7 (−12.8 to 2.3) | −2.7 (−8.1 to 2.7) | −1.6 (−5.6 to 2.4) | 0.426 |
| US total PD score† | −2.0 (−4.8 to 0.0) | −3.0 (−8.0 to 0.0) | −1.0 (−3.5 to 1.6) | 0.0 (−0.4 to 0.4) | 1.000 |
| US total number of erosions† | 0.0 (−0.1 to 1.0), n=46 | 1.0 (0.0 to 2.1), n=48 | 1.0 (−0.5 to −2.5) | 0.96 (−0.40 to 2.32) | 0.164 |
| Week 78 | |||||
| NTSJ | 28.1% | 24.6% | 0.84 (0.34 to 2.05) | 0.94 (0.37 to 2.41) | 0.904 |
| Achieved 26 weeks of remission | 18.3% | 14.5% | OR 0.76 (0.28 to 2.10) | OR 0.85 (0.30 to 2.41)* | 0.756 |
| ACR 2010 remission (Boolean) | 20.5% | 20.9% | OR 1.03 (0.40 to 2.63) | OR 1.04 (0.37 to 2.89) | 0.947 |
| ACR 2010 remission (SDAI≤3.3) | 38.5% | 39.5% | OR 1.05 (0.45 to 2.41) | OR 1.08 (0.45 to 2.59) | 0.867 |
| DAS44-CRP | −1.33 | −1.29 | 0.04 (−0.46 to 0.54) | 0.05 (−0.34 to 0.44) | 0.794 |
| Pain VAS† | −19.6 (−40.7 to −4.6) | −21.9 (−45.6 to −1.6) | −2.3 (−19.6 to 15.0) | 9.1 (−4.8 to 23.1)‡ | 0.195 |
| Fatigue VAS† | −17.7 (−37.1 to 8.4) | −19.0 (−46.3 to 1.2) | −1.4 (−17.9 to 15.2) | −3.6 (−23.9 to 16.8)‡ | 0.725 |
| Physician VAS† | −23.9 (−31.4 to −10.5) | −23.1 (−37.4 to −11.3) | 0.8 (−8.2 to 9.7) | 0.5 (−5.3 to 6.3)‡ | 0.871 |
| EMS† | −42.8 (−85.4 to −0.3) | −29.9 (−86.2 to −1.2) | 12.9 (−13.2 to 39.0)‡ | 1.8 (−14.8 to 18.4)‡ | 0.826 |
| HAQ-DI | −0.37 | −0.34 | 0.02 (−0.20 to 0.24) | 0.04 (−0.17 to 0.26) | 0.688 |
| SF-36 MCS | 2.94 | 2.48 | −0.46 (−5.48 to 4.57) | 1.42 (−3.10 to 5.95) | 0.533 |
| SF-36 PCS | 7.06 | 6.50 | −0.56 (−4.35 to 3.24) | −0.98 (−4.77 to 2.80) | 0.607 |
| EQ-5D-3L† | 0.151 (−0.004 to 0.276) | 0.102 (−0.002 to 0.236) | −0.049 (−0.156 to 0.057)‡ | −0.029 (−0.130 to 0.073)*‡ | 0.576 |
| ERO | 0.60 | 0.50 | −0.11 (−0.55 to 0.34) | −0.10 (−0.54 to 0.34) | 0.653 |
| JSN | 0.99 | 0.87 | −0.11 (−0.61 to 0.39) | −0.03 (−0.52 to 0.46) | 0.901 |
| mTSS | 1.59 | 1.37 | −0.22 (−0.90 to 0.46) | −0.10 (−0.74 to 0.54) | 0.761 |
| ERO† | 0.11 (0.00 to 0.71) | 0.02 (0.00 to 0.81) | −0.09 (−0.55 to 0.36)‡ | 0.00 (−0.22 to 0.22)*‡ | 1.000 |
| JSN† | 0.52 (0.04 to 1.44) | 0.62 (0.04 to 1.21) | 0.11 (−0.46 to 0.68)‡ | −0.12 (−0.62 to 0.38)‡ | 0.644 |
| mTSS† | 0.97 (0.45 to 2.27) | 1.09 (0.36 to 1.97) | 0.13 (−0.55 to 0.81)‡ | 0.15 (−0.48 to 0.77)‡ | 0.642 |
| Progression≤0.5 | 35.9% | 35.8% | OR 0.99 (0.36 to 2.74) | OR 0.99 (0.27 to 3.00)* | 0.982 |
| Progression≤SDC | 80.0% | 87.1% | OR 1.69 (0.53 to 5.37) | OR 1.39 (0.41 to 4.76)* | 0.598 |
| US GS>1PD>0 | 38.0%, n=46 | 41.6%, n=48 | OR 1.16 (0.49 to 2.75) | § | 0.740 |
| US total GS score† | 1.9 (−6.0 to 7.8) | −0.1 (−5.6 to 3.6) | −2.0 (−7.2 to 3.2) | −1.6 (−6.2 to 2.9) | 0.472 |
| US total PD score† | −2.0 (−3.9 to 0.0) | −1.5 (−7.7 to 0.1) | 0.5 (−1.9 to 3.0) | 0.6 (−1.0 to 2.2) | 0.434 |
| US total number of erosions† | 0.1 (0.0 to 2.1), n=46 | 1.1 (0.0 to 3.0), n=48 | 1.1 (−0.4 to 2.5) | 0.53 (−0.72 to 1.78) | 0.399 |
Mean (SD) or median (IQR) changes from baseline and between-group differences (95% CI) are presented for continuous variables; proportions and ORs (95% CI) are presented for nominal variables; results were adjusted for baseline values and study site unless otherwise indicated.
*Site adjustment pooled sites 2–4 to avoid model separation due to sparse data.
†Results of quantile regression; median (1st quartile, 3rd quartile) are presented for each group.
‡Difference between medians.
§Unadjusted results presented as US data only available at a single site, and adjusting for baseline values caused analysis model to fail.
ACR, American College of Rheumatology; DAS44-CRP, disease activity score based on RAI and SJC44; EQ-5D-3L, Euroqol 5-dimensional 3-level response standardised health outcome tool; EMS, early morning stiffness; ERO, van der Heijde modified Sharp erosion score; ESR, erythrocyte sedimentation rate; ETN, etanercept; GS, grey scale; HAQ-DI, Rasch-transformed health assessment questionnaire disability index score; JSN, van der Heijde modified Sharp joint space narrowing score; mTSS, van der Heijde modified total Sharpe score; MTX, methotrexate; NTSJ, no tender or swollen joints; PD, power Doppler; RAI, Ritchie articular index; RAQoL, Rasch-transformed rheumatoid arthritis quality of life score; RF, rheumatoid factor; SE, shared epitope; US, ultrasound; VAS, visual analogue scale.