Table 3.
Summary of findings: methotrexate inadequate response 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 (45 studies; 12 549 patients) | No of events/1000 patients at 1 year | Odds ratio | % | ||
| MTX | 127 | Reference | – | – | |
| MTX + abatacept (IV) | 357 (290 to 437) | 3.81 (2.80 to 5.33) | >99 | 5 | High |
| MTX + abatacept (SC) | 377 (284 to 488) | 4.16 (2.72 to 6.53) | >99 | 0 | High |
| MTX + adalimumab | 389 (330 to 462) | 4.37 (3.38 to 5.89) | >99 | 10 | High |
| MTX + etanercept | 642 (456 to 818) | 12.31 (5.76 to 30.78) | >99 | 3 | Moderate (study limitations) |
| MTX + golimumab (SC) | 395 (273 to 539) | 4.49 (2.57 to 8.01) | >99 | 3 | Moderate (study limitations, indirectness) |
| MTX + golimumab (IV) | 343 (207 to 514) | 3.58 (1.79 to 7.25) | >99 | 1 | Moderate (study limitations) |
| MTX + infliximab | 335 (264 to 422) | 3.46 (2.46 to 5.00) | >99 | 6 | High |
| MTX + rituximab | 343 (241 to 477) | 3.59 (2.18 to 6.27) | >99 | 3 | High |
| MTX + tocilizumab (4 mg/kg) | 273 (171 to 399) | 2.57 (1.42 to 4.56) | >99 | 2 | High |
| MTX + tocilizumab (8 mg/kg) | 377 (264 to 499) | 4.16 (2.46 to 6.85) | >99 | 3 | High |
| MTX + tofacitinib | 441 (325 to 568) | 5.42 (3.31 to 9.01) | >99 | 3 | High |
| MTX + hydroxychloroquine/chloroquine | 566 (241 to 871) | 8.94 (2.18 to 46.14) | >99 | 0 | Low (high imprecision) |
| MTX + IM gold | 704 (228 to 988) | 16.34 (2.03 to 553.42) | >99 | 1 | Very low (extreme imprecision) |
| MTX + leflunomide | 453 (245 to 703) | 5.69 (2.23 to 16.27) | >99 | 1 | Moderate (imprecision) |
| MTX + sulfasalazine | 267 (67 to 667) | 2.50 (0.49 to 13.76) | 87 | 0 | Low (high imprecision) |
| MTX + sulfasalazine + hydroxychloroquine | 605 (394 to 818) | 10.51 (4.46 to 30.81) | >99 | 0 | Moderate (study limitations) |
| Radiographic progression (10 studies; 3238 patients) | Mean change on Sharp-VdH scale over 1 year (points) | Standardized mean difference | % | ||
| MTX | 3.35 | Reference | – | – | |
| MTX + abatacept (IV) | 1.45 (−5.85 to 8.80) | −0.30 (−1.44 to 0.85) | 84 | 1 | Moderate (imprecision) |
| MTX + abatacept (SC) | 0.26 (−9.65 to 11.10) | −0.48 (−2.03 to 1.21) | 86 | 0 | Moderate (imprecision) |
| MTX + adalimumab | 0.51 (−6.42 to 7.96) | −0.44 (−1.53 to 0.72) | 90 | 1 | Moderate (study limitations, imprecision) |
| MTX + etanercept | −0.49 (−12.09 to 11.06) | −0.60 (−2.41 to 1.21) | 87 | 0 | Moderate (imprecision) |
| MTX + golimumab (SC) | 2.44 (−2.77 to 7.66) | −0.14 (−0.96 to 0.67) | 76 | 2 | Low (study limitations, inconsistency, indirectness, imprecision) |
| MTX + golimumab (IV) | 0.52 (−6.56 to 7.98) | −0.44 (−1.55 to 0.73) | 89 | 1 | Low (study limitations, imprecision) |
| MTX + infliximab | −1.08 (−8.34 to 6.35) | −0.69 (−1.83 to 0.47) | 94 | 1 | Low (study limitations, imprecision) |
| MTX + sulfasalazine + hydroxychloroquine | 0.70 (−9.58 to 11.05) | −0.41 (−2.02 to 1.20) | 82 | 0 | Low (indirectness, imprecision) |
| Withdrawals due to adverse events (53 studies; 9950 patient years) | No of events/1000 patients in 1 year | Rate ratio | % | ||
| MTX | 73 | Reference | – | – | |
| MTX + abatacept (IV) | 54 (31 to 90) | 0.76 (0.44 to 1.30) | 85 | 6 | High |
| MTX + abatacept (SC) | 39 (21 to 72) | 0.55 (0.28 to 1.03) | 97 | 0 | Moderate (indirectness) |
| MTX + adalimumab | 100 (67 to 155) | 1.44 (0.95 to 2.30) | 4 | 8 | High |
| MTX + certolizumab | 99 (56 to 196) | 1.42 (0.79 to 2.99) | 13 | 4 | Low (study limitations, indirectness) |
| MTX + etanercept | 89 (40 to 195) | 1.28 (0.56 to 2.92) | 29 | 3 | Moderate (study limitations) |
| MTX + golimumab (SC) | 72 (28 to 184) | 1.02 (0.39 to 2.78) | 48 | 3 | Low (study limitations, indirectness) |
| MTX + golimumab (IV) | 92 (26 to 370) | 1.32 (0.36 to 6.31) | 34 | 1 | Low (study limitations, imprecision) |
| MTX + infliximab | 112 (70 to 179) | 1.62 (0.99 to 2.70) | 3 | 6 | High |
| MTX + rituximab | 141 (53 to 376) | 2.07 (0.74 to 6.45) | 8 | 3 | Moderate (imprecision) |
| MTX + tocilizumab (4 mg/kg) | 112 (67 to 191) | 1.63 (0.95 to 2.90) | 4 | 3 | High |
| MTX + tocilizumab (8 mg/kg) | 118 (74 to 188) | 1.71 (1.01 to 2.84) | 2 | 5 | High |
| MTX + tofacitinib | 87 (52 to 152) | 1.24 (0.74 to 2.26) | 21 | 4 | High |
| MTX + ciclosporin | 212 (84 to 503) | 3.27 (1.20 to 9.57) | 1 | 2 | Low (indirectness, imprecision) |
| MTX + IM gold | 260 (35 to 999) | 4.12 (0.49 to 102.75) | 10 | 1 | Very low (extreme imprecision) |
| MTX + leflunomide | 127 (53 to 290) | 1.86 (0.74 to 4.68) | 8 | 1 | Moderate (imprecision) |
| MTX + sulfasalazine + hydroxychloroquine | 125 (62 to 249) | 1.82 (0.87 to 3.92) | 5 | 0 | Moderate (imprecision) |
CrI=credible interval; IM=intramuscular; IV=intravenous; MTX=methotrexate; SC= subcutaneous; VdH= van der Heijde.