Table S4.
Combination therapy network meta-analysis sensitivity analysis results for American College of Rheumatology (ACR) criteria scores of 20, 50, and 70 end point
| OR v DMARD (95% CrI)‡ | |||
|---|---|---|---|
|
|
|||
| ACR 20 | ACR 50 | ACR 70† | |
| Base case: random effects | |||
| ABA 10 mg/kg/4 weeks + DMARD | 3.255 (2.056, 5.159)‡ | 3.633 (2.093, 6.341)‡ | 3.954 (1.974, 8.8)‡ |
| ADA 40 mg/2 weeks + DMARD | 3.439 (2.187, 5.303)‡ | 3.87 (2.303, 6.598)‡ | 3.868 (1.91, 7.83)‡ |
| CZP 200 mg/2 weeks + DMARD | 11.06 (6.055, 21.06)‡ | 9.773 (4.604, 22.65)‡ | 13.18 (4.489, 43.5)‡ |
| ETN 2 × 25 mg/week + DMARD | 9.341 (4.845, 19.29)‡ | 11.15 (4.947, 27.95)‡ | 20.69 (4.921, 158.6)‡ |
| GOL 50 mg/4 weeks + DMARD | 3.387 (1.604, 6.863)‡ | 4.917 (2.051, 12.34)‡ | 4.988 (1.401, 18.28)‡ |
| INF 3 mg/kg/8 weeks + DMARD | 3.347 (2.271, 4.983)‡ | 3.602 (2.246, 5.924)‡ | 3.694 (2.021, 7.307)‡ |
| RTX 2 × 1000 mg + DMARD | 3.716 (1.915, 7.418)‡ | 4.103 (1.821, 9.73)‡ | 2.644 (0.909, 8.387) |
| TOC 8 mg/kg/4 weeks + DMARD | 4.399 (2.704, 7.125)‡ | 5.401 (2.911, 9.561)‡ | 7.656 (3.442, 16.5)‡ |
| As base case, but excluding MTX-naïve studies (MTX-experienced population) | |||
| ABA 10 mg/kg/4 weeks + DMARD | 3.31 (1.83, 5.52)‡ | 3.86 (1.91, 7.09)‡ | 4.91 (1.87, 11.1)‡ |
| ADA 40 mg/2 weeks + DMARD | 3.65 (2.04, 6.12)‡ | 4.27 (2.17, 7.75)‡ | 4.17 (1.67, 8.92)‡ |
| CZP 200 mg/2 weeks + DMARD | 12 (5.46, 23.67)‡ | 10.99 (4.08, 24.9)‡ | 17.01 (3.97, 52.62)‡ |
| ETN 2 × 25 mg/week + DMARD | 12.08 (3.83, 30.26)‡ | 28.5 (5.23, 104.6)‡ | 111 (3.04, 702.1)‡ |
| GOL 50 mg/4 weeks + DMARD | 3.67 (1.46, 7.69)‡ | 5.91 (1.96, 13.91)‡ | 6.62 (1.29, 20.6)‡ |
| INF 3 mg/kg/8 weeks + DMARD | 3.87 (2.24, 6.3)‡ | 4.02 (2.08, 7.16)‡ | 4.06 (1.63, 9.1)‡ |
| RTX 2 × 1000 mg + DMARD | 4.07 (1.74, 8.21)‡ | 4.67 (1.63, 10.76)‡ | 3.71 (0.88, 10.88) |
| TOC 8 mg/kg/4 weeks + DMARD | 4.48 (1.97, 8.9)‡ | 5.25 (1.92, 11.62)‡ | 8.18 (2.14, 22.14)‡ |
| As base case, but excluding RAPID 1 and RAPID 2 | |||
| ABA 10 mg/kg/4 weeks + DMARD | 3.239 (1.951, 5.364)‡ | 3.608 (2.024, 6.503)‡ | 4.055 (1.914, 9.659)‡ |
| ADA 40 mg/2 weeks + DMARD | 3.418 (2.111, 5.53)‡ | 3.884 (2.252, 6.853)‡ | 3.885 (1.871, 8.409)‡ |
| CZP 200 mg/2 weeks + DMARD | NA | NA | NA |
| ETN 2 × 25 mg/week + DMARD | 9.477 (4.771, 19.78)‡ | 11.3 (4.84, 29.37)‡ | 21.2 (4.751, 157.8)‡ |
| GOL 50 mg/4 weeks + DMARD | 3.364 (1.563, 7.297)‡ | 4.979 (2.064, 12.92)‡ | 4.869 (1.38, 18.76)‡ |
| INF 3 mg/kg/8 weeks + DMARD | 3.343 (2.187, 5.148)‡ | 3.628 (2.203, 6.106)‡ | 3.767 (1.967, 7.976)‡ |
| RTX 2 × 1000 mg + DMARD | 3.732 (1.824, 7.873)‡ | 4.103 (1.792, 10.01)‡ | 2.685 (0.854, 9.246) |
| TOC 8 mg/kg/4 weeks + DMARD | 4.389 (2.539, 7.569)‡ | 5.371 (2.841, 9.792)‡ | 7.659 (3.288, 17.58)‡ |
| As base case, but excluding low-quality ETN studies | |||
| ABA 10 mg/kg/4 weeks + DMARD | 3.271 (2.309, 4.614)‡ | 3.614 (2.057, 6.371)‡ | 4.063 (1.873, 9.751)‡ |
| ADA 40 mg/2 weeks + DMARD | 3.439 (2.375, 4.934)‡ | 3.876 (2.289, 6.699)‡ | 3.918 (1.837, 8.591)‡ |
| CZP 200 mg/2 weeks + DMARD | 10.93 (6.786, 18.51)‡ | 9.78 (4.502, 22.36)‡ | 13.37 (4.062, 54.14)‡ |
| ETN 2 × 25 mg/week + DMARD | 8.53 (4.776, 16.04)‡ | 11.55 (4.85, 29.68)‡ | 20.83 (4.695, 182.9)‡ |
| GOL 50 mg/4 weeks + DMARD | 3.505 (1.878, 6.219)‡ | 4.953 (2.037, 12.79)‡ | 4.954 (1.387, 19.9)‡ |
| INF 3 mg/kg/8 weeks + DMARD | 3.345 (2.485, 4.552)‡ | 3.614 (2.257, 5.956)‡ | 3.737 (1.912, 7.952)‡ |
| RTX 2 × 1000 mg + DMARD | 3.701 (2.139, 6.261)‡ | 4.046 (1.78, 9.64)‡ | 2.748 (0.838, 9.316) |
| TOC 8 mg/kg/4 weeks + DMARD | 4.411 (3.055, 6.369)‡ | 5.376 (2.918, 9.762)‡ | 7.541 (3.207, 18.02)‡ |
| As base case, but excluding studies in TNF-α-exposed patients | |||
| DMARD | – | – | – |
| ABA 10 mg/kg/4 weeks + DMARD | 3.479 (1.598, 7.638)‡ | 3.543 (1.59, 7.82)‡ | 3.345 (1.472, 8.01)‡ |
| ADA 40 mg/2 weeks + DMARD | 3.418 (1.906, 6.213)‡ | 3.908 (2.148, 7.375)‡ | 3.814 (1.915, 7.752)‡ |
| CZP 200 mg/2 weeks + DMARD | NA | NA | NA |
| ETN 2 × 25 mg/week + DMARD | 9.755 (4.387, 22.63)‡ | 11.32 (4.564, 31.03)‡ | 19.55 (4.814, 147.4)‡ |
| GOL 50 mg/4 weeks + DMARD | 3.315 (1.292, 8.238)‡ | 5.2 (1.905, 14.96)‡ | 4.722 (1.449, 18.3)‡ |
| INF 3 mg/kg/8 weeks + DMARD | 3.457 (1.926, 6.357)‡ | 4.08 (2.169, 7.935)‡ | 4.224 (2.137, 9.672)‡ |
| RTX 2 × 1000 mg + DMARD | 3.813 (1.576, 9.494)‡ | 4.145 (1.593, 11.29)‡ | 2.671 (0.934, 8.725) |
| TOC 8 mg/kg/4 weeks + DMARD | NA | NA | NA |
| As base case, but including TEMPO | |||
| ABA 10 mg/kg/4 weeks + DMARD | 3.249 (1.767, 6.024)‡ | 3.629 (1.916, 6.932)‡ | 4.11 (1.92, 9.757)‡ |
| ADA 40 mg/2 weeks + DMARD | 3.402 (1.947, 5.956)‡ | 3.896 (2.159, 7.215)‡ | 3.853 (1.836, 8.394)‡ |
| CZP 200 mg/2 weeks + DMARD | 11.24 (5.128, 25.42)‡ | 9.821 (4.05, 25.4)‡ | 13.26 (4.306, 48.4)‡ |
| ETN 2 × 25 mg/week + DMARD | 5.137 (2.816, 10.08)‡ | 5.482 (2.891, 11.75)‡ | 6.448 (2.832, 19.11)‡ |
| GOL 50 mg/4 weeks + DMARD | 3.308 (1.373, 8.033)‡ | 5.153 (1.943, 14.73)‡ | 4.801 (1.369, 18.95)‡ |
| INF 3 mg/kg/8 weeks + DMARD | 3.403 (2.048, 5.69)‡ | 3.664 (2.149, 6.397)‡ | 3.769 (1.946, 7.951)‡ |
| RTX 2 × 1000 mg + DMARD | 3.813 (1.631, 8.947)‡ | 4.13 (1.648, 10.85)‡ | 2.688 (0.878, 9.141) |
| TOC 8 mg/kg/4 weeks + DMARD | 4.392 (2.317, 8.34)‡ | 5.344 (2.648, 10.42)‡ | 7.655 (3.283, 17.96)‡ |
Notes:
‡
Licensed combination had significantly higher odds (based on the 95% CrI) compared to DMARD alone;
†
for the ACR 70 network meta-analysis, a continuity correction (0.5) was applied to the data.
Abbreviations: ABA, abatacept; ADA, adalimumab; ANA, anakinra; CrI, credible interval (Bayesian probability interval); CZP, certolizumab pegol; DMARD, disease-modifying antirheumatic drug (MTX or SUL); ETN, etanercept; exp, experienced; GOL, golimumab; INF, infliximab; MTX, methotrexate; NA, not applicable; OR, odds ratio; RTX, rituximab; SUL, sulfasalazine; TNF, tumor necrosis factor; TOC, tocilizumab.