Table 2.
Summary of findings: methotrexate naive patients
| Intervention | Absolute risk (95% CrI) | Average treatment effect relative to oral MTX (95% CrI) | Probability treatment superior to oral MTX | No of trials providing direct evidence | Quality of evidence |
|---|---|---|---|---|---|
| ACR50 (29 studies; 10 697 patients) | No of events/1000 patients at 1 year | Odds ratio | % | ||
| MTX | 405 | Reference | – | – | – |
| MTX + abatacept (IV) | 555 (407 to 699) | 1.84 (1.01 to 3.42) | 98 | 1 | High |
| MTX + abatacept (SC) | 574 (390 to 730) | 1.98 (0.94 to 3.97) | 97 | 1 | High |
| MTX + adalimumab | 588 (508 to 661) | 2.10 (1.52 to 2.87) | >99 | 4 | High |
| IM/SC MTX + adalimumab | 601 (353 to 805) | 2.22 (0.80 to 6.06) | 94 | 0 | Moderate (imprecision) |
| MTX + certolizumab | 504 (361 to 646) | 1.49 (0.83 to 2.68) | 93 | 1 | Moderate (study limitations) |
| MTX + etanercept | 671 (578 to 757) | 3.00 (2.02 to 4.59) | >99 | 2 | High |
| MTX + golimumab (SC) | 476 (315 to 638) | 1.33 (0.68 to 2.59) | 83 | 1 | Moderate (study limitations) |
| MTX + infliximab | 580 (470 to 719) | 2.03 (1.30 to 3.77) | >99 | 3 | High |
| MTX + rituximab | 622 (469 to 750) | 2.42 (1.30 to 4.42) | 99 | 1 | High |
| MTX + tocilizumab (4 mg/kg) | 529 (392 to 665) | 1.66 (0.95 to 2.92) | 97 | 1 | Moderate (study limitations) |
| MTX + tocilizumab (8 mg/kg) | 565 (426 to 696) | 1.91 (1.09 to 3.36) | 98 | 2 | High |
| MTX + tofacitinib | 674 (416 to 864) | 3.04 (1.05 to 9.37) | 98 | 1 | Moderate (imprecision) |
| MTX + ciclosporin | 539 (370 to 695) | 1.72 (0.86 to 3.36) | 94 | 1 | Low (indirectness, imprecision, study limitations) |
| IM/SC MTX + ciclosporin | 516 (234 to 803) | 1.57 (0.44 to 6.01) | 75 | 0 | Low (imprecision, study limitations) |
| MTX + hydroxychloroquine/chloroquine | 346 (136 to 663) | 0.78 (0.23 to 2.90) | 35 | 0 | Moderate (imprecision) |
| MTX + sulfasalazine | 427 (219 to 654) | 1.10 (0.41 to 2.78) | 57 | 1 | Low (indirectness, imprecision, study limitations) |
| MTX + sulfasalazine + hydroxychloroquine | 612 (442 to 765) | 2.32 (1.17 to 4.79) | 99 | 0 | Moderate (indirectness) |
| IM/SC MTX | 434 (288 to 595) | 1.13 (0.59 to 2.16) | 65 | 1 | Moderate (study limitations) |
| Radiographic progression (18 studies; 7594 patients) | Mean change on Sharp-VdH scale over 1 year (points) | Standardized mean difference | % | ||
| MTX | 2.34 | Reference | – | – | |
| MTX + abatacept (IV) | 1.11 (−1.29 to 3.47) | −0.20 (−0.60 to 0.19) | 88 | 1 | Moderate (imprecision) |
| MTX + adalimumab | 0.09 (−1.52 to 1.88) | −0.37 (−0.64 to −0.08) | 99 | 2 | High |
| MTX + certolizumab | −0.01 (−1.74 to 1.74) | −0.39 (−0.68 to −0.10) | 99 | 2 | Moderate (study limitations) |
| MTX + etanercept | 0.12 (−1.19 to 1.67) | −0.37 (−0.59 to −0.11) | 99 | 3 | High |
| MTX + golimumab (SC) | 1.57 (−0.87 to 4.08) | −0.13 (−0.53 to 0.29) | 76 | 1 | Low (study limitations, imprecision) |
| MTX + infliximab | −0.26 (−2.59 to 2.10) | −0.43 (−0.82 to −0.04) | 98 | 1 | High |
| MTX + rituximab | 0.03 (−2.40 to 2.42) | −0.38 (−0.79 to 0.01) | 97 | 1 | Moderate (imprecision) |
| MTX + tocilizumab (4 mg/kg) | 0.84 (−1.64 to 3.30) | −0.25 (−0.66 to 0.16) | 91 | 1 | Moderate (study limitations) |
| MTX + tocilizumab (8 mg/kg) | 0.14 (−2.28 to 2.54) | −0.37 (−0.77 to 0.03) | 97 | 1 | Moderate (study limitations) |
| MTX + tofacitinib | 1.09 (−2.78 to 5.17) | −0.21 (−0.85 to 0.47) | 73 | 1 | Moderate (imprecision) |
| MTX + ciclosporin | 1.07 (−0.68 to 2.94) | −0.21 (−0.50 to 0.10) | 92 | 2 | Low (study limitations, imprecision) |
| MTX + sulfasalazine + hydroxychloroquine | 2.14 (−2.18 to 6.69) | −0.03 (−0.75 to 0.72) | 54 | 0 | Moderate (imprecision) |
| Withdrawals due to adverse events (37 studies; 10 528 patient years) | No of events/1000 patients in 1 year | Rate ratio | % | ||
| MTX | 76 | Reference | – | – | |
| MTX + abatacept (IV) | 52 (15 to 163) | 0.70 (0.21 to 2.35) | 74 | 1 | High |
| MTX + abatacept (SC) | 71 (15 to 310) | 0.97 (0.20 to 4.89) | 52 | 1 | Moderate (imprecision) |
| MTX + adalimumab | 88 (46 to 153) | 1.21 (0.63 to 2.18) | 24 | 4 | High |
| IM/SC MTX + adalimumab | 60 (5.1 to 458) | 0.81 (0.07 to 8.06) | 58 | 0 | Moderate (imprecision) |
| MTX + etanercept | 59 (33 to 117) | 0.80 (0.45 to 1.64) | 77 | 3 | High |
| MTX + golimumab (SC) | 164 (49 to 520) | 2.36 (0.67 to 9.67) | 8 | 1 | Low (study limitations, imprecision) |
| MTX + infliximab | 175 (69 to 448) | 2.53 (0.94 to 7.81) | 3 | 4 | Moderate (imprecision) |
| MTX + rituximab | 61 (17 to 204) | 0.83 (0.22 to 3.01) | 62 | 1 | High |
| MTX + tocilizumab (4 mg/kg) | 96 (35 to 249) | 1.33 (0.46 to 3.77) | 25 | 1 | Low (study limitations, imprecision) |
| MTX + tocilizumab (8 mg/kg) | 158 (61 to 384) | 2.26 (0.82 to 6.38) | 5 | 1 | Low (study limitations, imprecision) |
| MTX + tofacitinib | 66 (13 to 293) | 0.90 (0.17 to 4.56) | 55 | 1 | Moderate (imprecision) |
| MTX + azathioprine | 356 (113 to 842) | 5.79 (1.58 to 24.31) | 1 | 3 | Moderate (indirectness) |
| MTX + ciclosporin | 77 (28 to 166) | 1.06 (0.37 to 2.38) | 44 | 2 | Moderate (indirectness) |
| IM/SC MTX + ciclosporin | 491 (71 to 999) | 8.89 (0.98 to 139.30) | 3 | 0 | Very low (extreme imprecision, indirectness) |
| MTX + hydroxychloroquine/chloroquine | 98 (30 to 392) | 1.35 (0.40 to 5.26) | 30 | 1 | Low (imprecision) |
| MTX + sulfasalazine | 95 (49 to 190) | 1.31 (0.67 to 2.78) | 21 | 4 | Moderate (indirectness) |
| MTX + sulfasalazine + hydroxychloroquine | 49 (21 to 109) | 0.67 (0.28 to 1.51) | 84 | 2 | Moderate (imprecision) |
| IM/SC MTX | 131 (42 to 399) | 1.85 (0.56 to 6.69) | 14 | 1 | Moderate (imprecision) |
CrI=credible interval; IM=intramuscular; IV=intravenous; MTX=methotrexate; SC=subcutaneous; VdH=van der Heijde.