Table 3.
Predictors of loss of remission in all treatment groups in the double-blind period
| Predictora | Adjusted hazard ratiob (95% CI) | ||
|---|---|---|---|
| ETN 50 mg + MTX n = 74 |
ETN 25 mg + MTX n = 56 |
MTX n = 66 |
|
| Loss of DAS28 remission at single time point in double-blind period | |||
| Lack of sustained DAS28 remission | 2.32 (1.44, 3.73) | 2.59 (1.48, 4.55) | 1.85 (1.24, 2.77) |
| Sustained weighted DAS28 remission | 0.67 (0.56, 0.80) | 0.71 (0.59, 0.86) | 0.79 (0.68, 0.92) |
| DAS28 at week 36 | 2.44 (1.59, 3.73) | 2.81 (1.70, 4.63) | 1.74 (1.20, 2.51) |
| DAS28 at week 40 | 3.24 (2.48, 4.23) | 5.88 (4.05, 8.53) | 2.26 (1.88, 2.71) |
| Change in DAS28 from week 36 to 40 | 3.24 (2.48, 4.23) | 5.88 (4.05, 8.53) | 2.26 (1.88, 2.71) |
| ESR at week 40 | 1.05 (1.02, 1.08) | 1.05 (1.02, 1.07) | 1.02 (1.01, 1.03) |
| Change in ESR from week 36 to 40 | 1.09 (1.06, 1.12) | 1.07 (1.04, 1.10) | 1.02 (1.01, 1.03) |
| Sustained weighted SDAI remission | 0.81 (0.58, 1.11) | 0.49 (0.30, 0.78) | 0.80 (0.60, 1.08) |
| SDAI at week 40 | 1.12 (1.08, 1.16) | 1.24 (1.17, 1.32) | 1.08 (1.06, 1.11) |
| Change in SDAI from week 36 to 40 | 1.13 (1.09, 1.18) | 1.23 (1.16, 1.30) | 1.09 (1.06, 1.12) |
| Sustained weighted CDAI remission | 0.87 (0.65, 1.17) | 0.49 (0.32, 0.75) | 0.85 (0.64, 1.13) |
| CDAI at week 40 | 1.12 (1.08, 1.16) | 1.24 (1.17, 1.31) | 1.09 (1.06, 1.12) |
| Change in CDAI from week 36 to 40 | 1.13 (1.09, 1.18) | 1.23 (1.16, 1.30) | 1.09 (1.07, 1.12) |
| PGA at week 40 | 1.50 (1.23, 1.81) | 1.73 (1.40, 2.12) | 1.26 (1.15, 1.39) |
| Change in PGA from week 36 to 40 | 1.52 (1.23, 1.88) | 1.42 (1.10, 1.83) | 1.25 (1.13, 1.38) |
| PtGA at week 40 | 1.27 (1.14, 1.42) | 1.26 (1.11, 1.43) | 1.25 (1.15, 1.36) |
| Change in PtGA from week 36 to 40 | 1.28 (1.14, 1.45) | 1.49 (1.26, 1.78) | 1.28 (1.17, 1.39) |
| General health VAS at week 40 | 1.03 (1.02, 1.04) | 1.02 (1.01, 1.03) | 1.02 (1.02, 1.03) |
| Change in general health VAS from week 36 to 40 | 1.04 (1.02, 1.05) | 1.03 (1.02, 1.05) | 1.03 (1.02, 1.04) |
| HAQ score at week 40 | 2.00 (1.31, 3.06) | 1.50 (0.94, 2.38) | 2.04 (1.47, 2.83) |
| Change in HAQ score from week 36 to 40 | 2.16 (1.11, 4.20) | 3.40 (1.75, 6.59) | 3.41 (2.12, 5.46) |
| TJC at week 40 | 1.15 (1.09, 1.22) | 1.46 (1.31, 1.63) | 1.22 (1.14, 1.30) |
| Change in TJC from week 36 to 40 | 1.15 (1.08, 1.22) | 1.55 (1.37, 1.76) | 1.24 (1.16, 1.32) |
| SJC at week 40 | 1.11 (0.98, 1.26) | 1.44 (1.26, 1.65) | 1.18 (1.09, 1.27) |
| Change in SJC from week 36 to 40 | 1.31 (1.14, 1.50) | 1.40 (1.19, 1.64) | 1.23 (1.13, 1.35) |
| Pain VAS at week 40 | 1.02 (1.01, 1.03) | 1.03 (1.01, 1.04) | 1.02 (1.01, 1.03) |
| Change in pain VAS from week 36 to 40 | 1.03 (1.01, 1.04) | 1.05 (1.04, 1.07) | 1.03 (1.02, 1.03) |
| Loss of DAS28 remission and change in DAS28 ≥ 0.6 in double-blind period | |||
| Lack of sustained DAS28 remission | 2.82 (1.64, 4.85) | 2.59 (1.44, 4.66) | 1.98 (1.33, 2.96) |
| Sustained weighted DAS28 remission | 0.68 (0.57, 0.82) | 0.68 (0.55, 0.83) | 0.78 (0.67, 0.91) |
| DAS28 at week 36 | 1.21 (0.80, 1.83) | 2.04 (1.25, 3.34) | 1.35 (0.95, 1.90) |
| DAS28 at week 40 | 3.55 (2.67, 4.71) | 7.18 (4.79, 10.75) | 2.65 (2.17, 3.23) |
| Change in DAS28 from week 36 to 40 | 3.55 (2.67, 4.71) | 7.18 (4.79, 10.75) | 2.65 (2.17, 3.23) |
| ESR at week 40 | 1.05 (1.02, 1.08) | 1.05 (1.02, 1.07) | 1.02 (1.01, 1.03) |
| Change in ESR from week 36 to 40 | 1.09 (1.05, 1.12) | 1.07 (1.04, 1.10) | 1.02 (1.01, 1.03) |
| Sustained weighted SDAI remission | 0.71 (0.49, 1.01) | 0.47 (0.30, 0.76) | 0.81 (0.60, 1.09) |
| SDAI at week 40 | 1.13 (1.09, 1.18) | 1.29 (1.21, 1.38) | 1.10 (1.07, 1.12) |
| Change in SDAI from week 36 to 40 | 1.15 (1.10, 1.20) | 1.26 (1.19, 1.34) | 1.11 (1.08, 1.14) |
| Sustained weighted CDAI remission | 0.80 (0.58, 1.10) | 0.48 (0.31, 0.74) | 0.85 (0.64, 1.14) |
| CDAI at week 40 | 1.13 (1.09, 1.18) | 1.28 (1.21, 1.36) | 1.10 (1.07, 1.13) |
| Change in CDAI from week 36 to 40 | 1.14 (1.10, 1.19) | 1.26 (1.19, 1.34) | 1.11 (1.08, 1.14) |
| HAQ at week 40 | 1.74 (1.08, 2.80) | 1.85 (1.15, 2.98) | 2.17 (1.55, 3.04) |
| Change in HAQ from week 36 to 40 | 1.74 (0.85, 3.56) | 4.21 (2.11, 8.39) | 4.24 (2.61, 6.89) |
| PGA at week 40 | 1.55 (1.26, 1.91) | 1.92 (1.54, 2.38) | 1.30 (1.18, 1.43) |
| Change in PGA from week 36 to 40 | 1.70 (1.36, 2.11) | 1.60 (1.23, 2.08) | 1.30 (1.17, 1.43) |
| PtGA at week 40 | 1.25 (1.12, 1.40) | 1.34 (1.17, 1.53) | 1.30 (1.20, 1.41) |
| Change in PtGA from week 36 to 40 | 1.27 (1.12, 1.43) | 1.52 (1.27 1.82) | 1.35 (1.23, 1.47) |
| General health at week 40 | 1.03 (1.01, 1.04) | 1.03 (1.01, 1.04) | 1.03 (1.01, 1.04) |
| Change in general health from week 36 to 40 | 1.04 (1.02, 1.06) | 1.03 (1.02, 1.05) | 1.03 (1.02, 1.04) |
| TJC at week 40 | 1.16 (1.10, 1.23) | 1.50 (1.34, 1.69) | 1.25 (1.17, 1.34) |
| Change in TJC from week 36 to 40 | 1.16 (1.10, 1.23) | 1.59 (1.39, 1.80) | 1.28 (1.20, 1.37) |
| SJC at week 40 | 1.18 (1.03, 1.34) | 1.51 (1.32, 1.73) | 1.17 (1.08, 1.26) |
| Change in SJC from week 36 to 40 | 1.35 (1.16, 1.56) | 1.49 (1.27, 1.75) | 1.28 (1.17, 1.40) |
| Pain VAS at week 40 | 1.02 (1.01, 1.03) | 1.03 (1.02, 1.05) | 1.02 (1.01, 1.03) |
| Change in pain VAS from week 36 to 40 | 1.03 (1.01, 1.04) | 1.05 (1.03, 1.07) | 1.03, (1.02, 1.04) |
| ETN 50 mg + MTX n = 72 |
ETN 25 mg + MTX n = 60 |
MTX n = 53 |
|
| Loss of SDAI remission at single time point in double-blind period | |||
| Lack of sustained SDAI remission | 2.57 (0.90, 7.32) | 1.86 (0.55, 6.24) | 2.92 (1.08, 7.94) |
| Sustained weighted SDAI remission | 0.67 (0.49, 0.90) | 0.62 (0.45, 0.86) | 0.68 (0.51, 0.90) |
| SDAI at week 36 | 1.56 (1.06, 2.29) | 2.00 (1.34, 3.00) | 1.14 (0.80, 1.62) |
| SDAI at week 40 | 1.13 (1.07, 1.19) | 1.18 (1.09, 1.29) | 1.05 (1.02, 1.08) |
| Change in SDAI from week 36 to 40 | 1.13 (1.07, 1.19) | 1.18 (1.09, 1.29) | 1.05 (1.02, 1.08) |
| Sustained weighted CDAI remission | 0.71 (0.53, 0.95) | 0.61 (0.44, 0.83) | 0.71 (0.54, 0.92) |
| CDAI at week 40 | 1.12 (1.07, 1.18) | 1.18 (1.09, 1.29) | 1.05 (1.02, 1.08) |
| Change in CDAI from week 36 to 40 | 1.12 (1.07, 1.18) | 1.19 (1.09, 1.29) | 1.05 (1.02, 1.08) |
| Sustained weighted DAS28 remission | 0.81 (0.63, 1.03) | 0.93 (0.71, 1.22) | 0.86 (0.67, 1.10) |
| DAS28 at week 40 | 1.76 (1.20, 2.59) | 1.70 (1.05, 2.77) | 1.46 (1.19, 1.79) |
| Change in DAS28 from week 36 to 40 | 2.09 (1.47, 2.96) | 2.55 (1.52, 4.28) | 1.62 (1.24, 2.11) |
| HAQ score at week 40 | 1.76 (0.90, 3.44) | 1.92 (0.86, 4.26) | 2.22 (1.17, 4.21) |
| Change in HAQ score from week 36 to 40 | 2.66 (0.89, 7.96) | 6.13 (1.69, 22.26) | 4.25 (1.83, 9.91) |
| PGA at week 40 | 1.77 (1.37, 2.29) | 1.79 (1.32, 2.42) | 1.27 (1.10, 1.47) |
| Change in PGA from week 36 to 40 | 1.69 (1.33, 2.14) | 1.88 (1.30, 2.70) | 1.26 (1.09, 1.46) |
| PtGA at week 40 | 1.37 (1.17, 1.61) | 1.72 (1.32, 2.24) | 1.30 (1.13, 1.50) |
| Change in PtGA from week 36 to 40 | 1.40 (1.20, 1.64) | 1.73 (1.32, 2.27) | 1.30 (1.14, 1.50) |
| General health VAS at week 40 | 1.04 (1.01, 1.07) | 1.04 (1.01, 1.06) | 1.02 (1.01, 1.04) |
| Change in general health VAS from week 36 to 40 | 1.05 (1.02, 1.07) | 1.04, (1.01, 1.06) | 1.03 (1.01, 1.04) |
| TJC at week 40 | 1.31 (1.10, 1.56) | 1.36 (1.11, 1.68) | 1.05 (1.00, 1.11) |
| Change in TJC from week 36 to 40 | 1.38 (1.14, 1.67) | 1.38 (1.13, 1.69) | 1.06 (1.00, 1.12) |
| SJC at week 40 | 1.31 (1.05, 1.63) | 1.15 (0.91, 1.44) | 1.17 (1.01, 1.36) |
| Change in SJC from week 36 to 40 | 1.30 (1.04, 1.63) | 1.15 (0.93, 1.44) | 1.17 (1.01, 1.35) |
| Pain VAS at week 40 | 1.03 (1.01, 1.05) | 1.05 (1.02, 1.08) | 1.03 (1.01, 1.04) |
| Change in pain VAS from week 36 to 40 | 1.04 (1.02, 1.06) | 1.05 (1.03, 1.09) | 1.03 (1.01, 1.05) |
| Loss of CDAI remission at single time point in double-blind period | |||
| Lack of sustained CDAI remission | 2.10 (0.82, 5.40) | 2.82 (0.83, 9.55) | 2.60 (1.04, 6.48) |
| Sustained weighted CDAI remission | 0.69 (0.51, 0.92) | 0.57 (0.42, 0.78) | 0.71 (0.55, 0.93) |
| CDAI at week 36 | 1.49 (1.04, 2.15) | 1.65 (1.14, 2.39) | 1.07 (0.76, 1.51) |
| CDAI at week 40 | 1.15 (1.09, 1.21) | 1.21 (1.11, 1.31) | 1.05 (1.02, 1.09) |
| Change in CDAI from week 36 to 40 | 1.15 (1.09, 1.21) | 1.21 (1.11, 1.31) | 1.05 (1.02, 1.09) |
| Sustained weighted SDAI remission | 0.63 (0.46, 0.87) | 0.59 (0.42, 0.81) | (0.68 (0.51, 0.90) |
| Sustained weighted DAS28 remission | 0.78 (0.61, 1.00) | 0.96 (0.76, 1.22) | 0.81 (0.63, 1.04) |
| DAS28 at week 40 | 1.95 (1.30, 2.91) | 2.12 (1.32, 3.38) | 1.51 (1.23, 1.86) |
| Change in DAS28 from week 36 to 40 | 2.11 (1.47, 3.01) | 2.87 (1.77, 4.66) | 1.71 (1.31, 2.22) |
| HAQ score at week 40 | 2.10 (1.10, 4.00) | 1.87 (0.85, 4.12) | 2.10 (1.10, 4.02) |
| Change in HAQ score from week 36 to 40 | 4.00 (1.38, 11.62) | 10.88 (3.35, 35.34) | 4.34 (1.86, 10.12) |
| PGA at week 40 | 1.93 (1.49, 2.49) | 1.90 (1.40, 2.56) | 1.30 (1.13, 1.50) |
| Change in PGA from week 36 to 40 | 1.83 (1.42, 2.35) | 2.07 (1.48, 2.91) | 1.30 (1.12, 1.51) |
| PtGA at week 40 | 1.45 (1.23, 1.70) | 1.82 (1.40, 2.37) | 1.32 (1.16, 1.51) |
| Change in PtGA from week 36 to 40 | 1.46 (1.24, 1.72) | 1.75 (1.35, 2.28) | 1.34 (1.17, 1.53) |
| General health VAS at week 40 | 1.05 (1.02, 1.08) | 1.04 (1.02, 1.06) | 1.03 (1.01, 1.04) |
| Change in general health VAS from week 36 to 40 | 1.05 (1.03, 1.08) | 1.04 (1.02, 1.07) | 1.03 (1.01, 1.04) |
| TJC at week 40 | 1.41 (1.18, 1.68) | 1.41 (1.15, 1.74) | 1.06 (1.01, 1.12) |
| Change in TJC from week 36 to 40 | 1.50 (1.24, 1.82) | 1.45 (1.19, 1.76) | 1.07 (1.01, 1.13) |
| SJC at week 40 | 1.40 (1.12, 1.74) | 1.19 (0.96, 1.49) | 1.20 (1.04, 1.39) |
| Change in SJC from week 36 to 40 | 1.39 (1.10, 1.74) | 1.20 (0.97, 1.49) | 1.20 (1.04, 1.39) |
| Pain VAS at week 40 | 1.04 (1.02, 1.06) | 1.05 (1.03, 1.08) | 1.03 (1.01, 1.04) |
| Change in pain VAS from week 36 to 40 | 1.04 (1.02, 1.06) | 1.06 (1.03, 1.09) | 1.03 (1.02, 1.05) |
CDAI Clinical Disease Activity Index, CI confidence interval, DAS28 Disease Activity Score based on a 28-joint count, ESR erythrocyte sedimentation rate, ETN etanercept, HAQ health assessment questionnaire, MTX methotrexate, PGA physician global assessment, PtGA patient global assessment, SDAI Simplified Disease Activity Index, SJC swollen joint count, TJC tender joint count, VAS visual analog scale
aIncluded factors were significant predictors of remission loss in at least one of the three treatment arms, except lack of sustained SDAI/CDAI remission, SJC at week 40, and change in SJC from week 30 to 40 for SDAI and CDAI loss of remission. Sustained remission predictors are weighted. Hazard ratios that are not statistically significant are reported in italics
bFrom Cox proportional hazards model for loss of response, adjusted for baseline of respective outcome (e.g., baseline DAS28, SDAI, or CDAI). Higher hazard ratios denote a higher likelihood of loss of remission. Results cannot be compared across treatment groups because separate models were used for each