4. Treatment effects relative to oral methotrexate for all minor efficacy outcomes.
|
Outcome Treatment effect |
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| Intervention | ACR20 | ACR70 | DAS‐28 remission | EULAR response | Radiographic non‐progression (Y/N) | Withdrawals due to inefficacy | DAS‐28 | HAQ‐DI | Pain VAS | SJC, change from baseline | Fatigue, change from baseline |
| OR | OR | OR | OR | OR | OR | MD | MD | MD | SMD |
SMD (methotrexate‐naïve) MD (methotrexate‐IR) |
|
| MTX‐naïve | |||||||||||
| MTX + abatacept (IV) | ‐‐ | 1.99 (0.71 to 5.30) | 2.33 (1.23 to 4.37) | ‐‐ | 1.42 (0.74 to 2.72) | NE | ‐0.74 (‐1.50 to 0.04) | ‐0.20 (‐0.37 to ‐0.03) | ‐‐ | ‐‐ | ‐‐ |
| MTX + abatacept (sc) | 1.56 (0.71 to 3.48) | 2.10 (0.70 to 6.25) | 1.76 (0.87 to 3.61) | ‐‐ | ‐‐ | 0.40 (0.07 to 2.20) | ‐0.51 (‐1.29 to 0.30) | ‐0.15 (‐0.36 to 0.05) | ‐‐ | ‐‐ | ‐‐ |
| MTX + adalimumab | 1.92 (1.38 to 2.76) | 2.44 (1.44 to 4.06) | 2.29 (1.64 to 3.03) | 3.60 (0.27 to 46.35) | 2.96 (2.05 to 4.48) | 0.21 (0.08 to 0.55) | ‐0.82 (‐1.41 to ‐0.28) | ‐0.22 (‐0.31 to ‐0.14) | ‐5.79 (‐8.92 to ‐2.86) | ‐‐ | ‐0.19 (‐2.69 to 2.33) |
| IM/sc MTX + adalimumab | 2.78 (0.92 to 8.55) | 3.52 (0.74 to 15.93) | ‐‐ | ‐‐ | ‐‐ | NE | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ |
| MTX + certolizumab | 1.43 (0.75 to 2.73) | 1.62 (0.59 to 4.41) | 2.16 (1.37 to 3.40) | 2.03 (0.16 to 27.02) | 4.24 (1.85 to 9.36) | 0.40 (0.09 to 1.77) | ‐0.60 (‐1.35 to 0.18) | ‐0.18 (‐0.34 to ‐0.02) | ‐4.47 (‐9.40 to 0.40) | ‐‐ | ‐‐ |
| MTX + etanercept | 2.66 (1.69 to 4.19) | 3.07 (1.58 to 6.06) | 2.74 (1.79 to 4.03) | ‐‐ | 2.92 (1.73 to 4.87) | 0.19 (0.07 to 0.46) | ‐‐ | ‐0.24 (‐0.34 to ‐0.14) | ‐11.04 (‐15.67 to ‐6.43) | ‐‐ | ‐0.28 (‐2.84 to 2.26) |
| MTX + golimumab (sc) | 1.41 (0.69 to 2.86) | 1.43 (0.48 to 4.25) | 1.50 (0.74 to 2.91) | 1.70 (0.13 to 22.03) | 2.07 (0.79 to 6.00) | 1.02 (0.15 to 6.71) | ‐‐ | ‐0.08 (‐0.27 to 0.11) | ‐‐ | ‐‐ | ‐‐ |
| MTX + infliximab | 2.16 (1.46 to 3.62) | 3.27 (1.74 to 7.23) | 1.52 (0.77 to 3.04) | ‐‐ | 3.09 (1.34 to 7.51) | 0.18 (0.04 to 0.86) | ‐0.57 (‐1.16 to 0.05) | ‐0.39 (‐0.56 to ‐0.22) | ‐‐ | ‐‐ | ‐‐ |
| MTX + rituximab | 2.30 (1.18 to 4.52) | 2.36 (0.83 to 6.79) | 3.27 (1.66 to 6.44) | ‐‐ | 2.19 (1.14 to 4.18) | ‐‐ | ‐1.19 (‐2.00 to ‐0.40) | ‐0.25 (‐0.43 to ‐0.07) | ‐‐ | ‐‐ | ‐‐ |
| MTX + tocilizumab (4 mg/kg) | 1.43 (0.78 to 2.64) | 1.63 (0.63 to 4.29) | 2.35 (1.31 to 4.20) | ‐‐ | ‐‐ | 0.30 (0.06 to 1.47) | ‐‐ | ‐0.27 (‐0.44 to ‐0.09) | ‐1.80 (‐7.40 to 3.79) | ‐‐ | ‐0.20 (‐2.73 to 2.36) |
| MTX+ tocilizumab (8 mg/kg) | 1.75 (0.94 to 3.21) | 2.10 (0.81 to 5.32) | 4.37 (2.46 to 7.82) | ‐‐ | ‐‐ | 0.07 (0.007 to 0.49) | ‐‐ | ‐0.24 (‐0.41 to ‐0.07) | ‐8.59 (‐13.95 to ‐3.12) | ‐‐ | ‐0.23 (‐2.75 to 2.33) |
| MTX + tofacitinib | 3.02 (1.05 to 9.65) | 1.06 (0.24 to 4.54) | 2.91 (0.82 to 12.59) | 4.63 (0.31 to 69.67) | ‐‐ | NE | ‐1.10 (‐2.25 to 0.05) | ‐‐ | ‐‐ | ‐‐ | ‐‐ |
| MTX + azathioprine | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | NE | ‐‐ | ‐‐ | ‐‐ | 0.006 (‐1.91 to 1.91) | ‐‐ |
| MTX + cyclosporine | 2.76 (1.09 to 7.39) | 1.86 (0.60 to 5.78) | 1.44 (0.86 to 2.45) | ‐‐ | 0.79 (0.27 to 2.12) | 0.85 (0.28 to 2.75) | ‐0.21 (‐0.78 to 0.35) | ‐0.19 (‐0.33 to ‐0.05) | ‐3.95 (‐10.81 to 2.77) | ‐‐ | ‐‐ |
| IM/sc MTX + cyclosporine | 1.01 (0.27 to 4.03) | 5.28 (0.85 to 33.45) | ‐‐ | ‐‐ | ‐‐ | NE | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ |
| MTX + hydroxychloroquine/ chloroquine | 0.67 (0.19 to 2.28) | 0.74 (0.12 to 4.90) | ‐‐ | ‐‐ | ‐‐ | NE | ‐‐ | ‐0.17 (‐0.50 to 0.14) | 0.18 (‐9.06 to 9.64) | ‐0.77 (‐3.15 to 1.59) | ‐‐ |
| MTX + sulfasalazine | 1.51 (0.85 to 2.64) | 1.61 (0.36 to 8.21) | ‐‐ | 1.59 (0.12 to 20.34) | 2.24 (0.60 to 10.49) | 0.89 (0.22 to 3.82) | ‐‐ | ‐0.06 (‐0.41 to 0.31) | ‐5.94 (‐11.77 to 0.10) | ‐0.68 (‐1.88 to 0.48) | ‐‐ |
| MTX + sulfasalazine + hydroxychloroquine | 2.30 (1.12 to 4.92) | 1.49 (0.47 to 5.27) | ‐‐ | 2.63 (0.20 to 33.51) | 1.41 (0.52 to 3.63) | 0.29 (0.07 to 1.02) | ‐‐ | ‐0.23 (‐0.36 to ‐0.08) | ‐9.39 (‐16.65 to ‐2.33) | ‐1.09 (‐3.42 to 1.27) | ‐‐ |
| IM/sc MTX | 1.46 (0.71 to 2.91) | 1.38 (0.47 to 3.82) | ‐‐ | ‐‐ | ‐‐ | 0.46 (0.05 to 4.11) | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ |
| MTX‐inadequate response | |||||||||||
| MTX + abatacept (IV) | 3.75 (2.93 to 4.84) | 4.17 (2.65 to 6.86) | 5.73 (3.41 to 10.73) | ‐‐ | ‐‐ | 0.20 (0.08 to 0.49) | ‐1.20 (‐1.55 to ‐0.86) | ‐0.32 (‐0.40 to ‐0.24) | ‐18.37 (‐23.15 to ‐13.49) | ‐0.60 (‐1.16 to ‐0.01) | ‐‐ |
| MTX + abatacept (sc) | 4.09 (2.99 to 5.96) | 5.00 (2.78 to 9.50) | 6.01 (3.07 to 13.97) | ‐‐ | ‐‐ | 0.47 (0.11 to 2.50) | ‐1.21 (‐1.74 to ‐0.70) | ‐0.31 (‐0.42 to ‐0.22) | ‐21.77 (‐27.48 to ‐15.81) | ‐0.64 (‐1.55 to 0.28) | ‐‐ |
| MTX + adalimumab | 3.60 (2.95 to 4.51) | 4.44 (3.06 to 6.89) | 4.82 (2.54 to 9.30) | 2.95 (1.13 to 7.99) | ‐‐ | 0.27 (0.10 to 0.71) | ‐0.86 (‐1.46 to ‐0.27) | ‐0.29 (‐0.37 to ‐0.21) | ‐12.41 (‐15.63 to ‐9.37) | ‐0.65 (‐1.07 to ‐0.24) | ‐‐ |
| MTX + certolizumab | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | 0.35 (0.14 to 0.89) | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ |
| MTX + etanercept | 7.30 (4.15 to 13.19) | 11.33 (3.17 to 53.51) | ‐‐ | ‐‐ | ‐‐ | 0.59 (0.08 to 2.84) | ‐1.50 (‐2.33 to ‐0.67) | ‐0.20 (‐0.39 to ‐0.02) | ‐24.48 (‐41.54 to ‐9.75) | ‐‐ | ‐‐ |
| MTX + golimumab (sc) | 3.94 (2.84 to 5.40) | 5.97 (2.59 to 14.72) | 5.90 (2.41 to 15.59) | 3.85 (2.17 to 6.74) | 1.43 (0.30 to 7.07) | 0.33 (0.05 to 1.52) | ‐1.30 (‐1.90 to ‐0.68) | ‐0.37 (‐0.46 to ‐0.27) | ‐‐ | ‐‐ | ‐5.35 (‐7.68 to ‐3.05) |
| MTX + golimumab (IV) | 3.92 (2.43 to 6.56) | 5.31 (1.83 to 16.87) | 4.19 (1.27 to 14.41) | ‐‐ | 2.55 (0.31 to 20.55) | 0.53 (0.01 to 35.46) | ‐1.20 (‐1.98 to ‐0.44) | ‐0.32 (‐0.46 to ‐0.17) | ‐‐ | ‐‐ | ‐5.40 (‐8.18 to ‐2.59) |
| MTX + infliximab | 3.21 (2.49 to 4.12) | 3.67 (2.20 to 6.31) | 3.91 (1.86 to 9.37) | 3.33 (1.61 to 7.10) | 7.86 (0.82 to 66.77) | 0.26 (0.07 to 0.73) | ‐0.89 (‐1.33 to ‐0.45) | ‐0.29 (‐0.41 to ‐0.18) | ‐‐ | ‐0.47 (‐1.06 to 0.11) | ‐‐ |
| MTX + rituximab | 3.42 (2.34 to 5.08) | 3.55 (1.64 to 7.78) | 4.53 (1.07 to 23.14) | 3.56 (2.20 to 6.21) | ‐‐ | 0.13 (0.02 to 0.39) | ‐1.07 (‐1.68 to ‐0.48) | ‐0.16 (‐0.36 to 0.04) | ‐‐ | ‐0.46 (‐1.29 to 0.35) | ‐3.81 (‐6.75 to ‐0.70) |
| MTX + tocilizumab (4 mg/kg) | 2.49 (1.63 to 3.90) | 2.16 (0.89 to 5.07) | 7.44 (1.99 to 34.88) | 3.05 (1.40 to 6.63) | ‐‐ | 0.16 (0.03 to 0.57) | ‐1.11 (‐1.85 to ‐0.38) | ‐0.18 (‐0.37 to 0.01) | ‐11.10 (‐17.53 to ‐4.51) | ‐0.42 (‐1.23 to 0.39) | ‐3.26 (‐6.47 to ‐0.22) |
| MTX+ tocilizumab (8 mg/kg) | 3.77 (2.52 to 5.53) | 4.41 (2.06 to 9.32) | 16.16 (5.25 to 59.96) | 7.37 (3.24 to 16.20) | ‐‐ | 0.07 (0.02 to 0.24) | ‐1.71 (‐2.27 to ‐1.14) | ‐0.21 (‐0.39 to ‐0.02) | ‐16.10 (‐22.36 to ‐9.43) | ‐0.62 (‐1.44 to 0.19) | ‐4.60 (‐7.87 to ‐1.50) |
| MTX + tofacitinib | 4.14 (2.86 to 6.32) | 8.86 (4.19 to 19.60) | 4.40 (1.67 to 11.78) | 3.57 (1.38 to 9.35) | ‐‐ | 0.43 (0.09 to 1.58) | ‐0.82 (‐1.33 to ‐0.32) | ‐0.28 (‐0.42 to ‐0.14) | ‐11.79 (‐16.28 to ‐7.36) | ‐0.54 (‐1.23 to 0.07) | ‐3.76 (‐8.95 to 1.32) |
| MTX + cyclosporine | 5.63 (2.76 to 12.10) | ‐‐ | ‐‐ | ‐‐ | ‐‐ | 0.10 (0.003 to 0.90) | ‐‐ | ‐0.28 (‐0.46 to ‐0.10) | ‐9.55 (‐18.64 to ‐0.41) | ‐0.49 (‐1.34 to 0.35) | ‐‐ |
| MTX + hydroxychloroquine/ chloroquine | 3.24 (0.79 to 11.36) | 4.28 (0.41 to 53.49) | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ |
| MTX + IM gold | 3.91 (1.31 to 11.54) | NE | ‐‐ | ‐‐ | ‐‐ | 0.13 (0.01 to 0.90) | ‐‐ | ‐0.11 (‐0.42 to 0.17) | ‐6.00 (‐25.27 to 13.54) | ‐0.40 (‐1.33 to 0.52) | ‐‐ |
| MTX + leflunomide | 3.59 (1.86 to 6.82) | 5.20 (1.22 to 29.24) | ‐‐ | ‐‐ | ‐‐ | 0.58 (0.11 to 3.12) | ‐‐ | ‐0.33 (‐0.48 to ‐0.18) | ‐16.98 (‐24.20 to ‐9.60) | ‐0.45 (‐1.28 to 0.36) | ‐‐ |
| MTX + sulfasalazine | 1.47 (0.34 to 5.19) | 2.03 (0.13 to 29.43) | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ | ‐‐ |
| MTX + sulfasalazine + hydroxychloroquine | 6.92 (3.48 to 14.02) | 5.13 (1.18 to 29.09) | ‐‐ | ‐‐ | ‐‐ | 0.84 (0.13 to 3.92) | ‐1.50 (‐2.52 to ‐0.51) | ‐0.18 (‐0.40 to 0.03) | ‐24.05 (‐41.74 to ‐8.45) | ‐‐ | ‐‐ |
Abbreviations: IM, intra‐muscular; IV, intravenous; MD, mean difference; MTX, methotrexate; NE, not estimable; OR, odds ratio; sc, subcutaneous; SMD, standardized mean difference