Table 8.
Results from combination therapy network meta-analysis study-level covariate analysis for American College of Rheumatology (ACR) criteria scores of 20, 50, and 70 end point
| Base case: random effects | OR v DMARD (95% CrI)‡ | ||
|---|---|---|---|
|
|
|||
| ACR 20 | ACR 50 | ACR 70† | |
| 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)‡ |
| Covariate analysis | |||
| ABA 10 mg/kg/4 weeks + DMARD | 3.314 (1.849, 5.878)‡ | 3.121 (1.656, 5.854)‡ | 2.994 (1.433, 6.802)‡ |
| ADA 40 mg/2 weeks + DMARD | 3.418 (2.051, 5.675)‡ | 3.862 (2.249, 6.904)‡ | 3.934 (2.035, 8.078)‡ |
| CZP 200 mg/2 weeks + DMARD | 11.18 (5.464, 23.63)‡ | 8.867 (3.968, 21.15)‡ | 10.5 (3.789, 37.14)‡ |
| ETN 2 × 25 mg/week + DMARD | 10.19 (3.733, 31.23)‡ | 24.67 (6.58, 109.5)‡ | 32.6 (4.276, 1399)‡ |
| GOL 50 mg/4 weeks + DMARD | 3.31 (1.436, 7.456)‡ | 6.091 (2.408, 16.59)‡ | 7.872 (2.3, 29.78)‡ |
| INF 3 mg/kg/8 weeks + DMARD | 3.371 (2.117, 5.416)‡ | 3.496 (2.131, 5.891)‡ | 3.758 (2.044, 7.593)‡ |
| RTX 2 × 1000 mg + DMARD | 3.809 (1.759, 8.296)‡ | 3.734 (1.556, 9.128)‡ | 2.208 (0.793, 7.004) |
| TOC 8 mg/kg/4 weeks + DMARD | 4.428 (2.483, 7.934)‡ | 5.335 (2.821, 9.869)‡ | 7.921 (3.773, 17.58)‡ |
| Coefficients (on log scale)‡ | Median (95% CrI) | ||
| βmtx: standard MTX dose | −0.037 (−1.092, 1.002) | −0.563 (−1.855, 0.631) | −1.775 (−4.292, 0.13) |
| βweeks: weeks of follow-up | −0.004 (−0.055, 0.046) | 0.039 (−0.018, 0.098) | 0.086 (0.012, 0.163)+ |
| Covariate analysis: adjusted odds ratios^ | OR v DMARD (95% CrI) | ||
| ABA 10 mg/kg/4 weeks + DMARD | 3.265 (1.879, 5.621)‡ | 3.396 (1.871, 6.122)‡ | 3.487 (1.77, 7.447)‡ |
| ADA 40 mg/2 weeks + DMARD | 3.374 (2.002, 5.65)‡ | 4.203 (2.421, 7.558)‡ | 4.58 (2.342, 9.481)‡ |
| CZP 200 mg/2 weeks + DMARD | 11.02 (5.441, 23.06)‡ | 9.647 (4.354, 22.61)‡ | 12.2 (4.501, 43.03)‡ |
| ETN 2 × 25 mg/week + DMARD | 10.04 (3.618, 31.17)‡ | 26.9 (6.909, 122.9)‡ | 38.2 (4.743, 1636)‡ |
| GOL 50 mg/4 weeks + DMARD | 3.268 (1.357, 7.651)‡ | 6.612 (2.524, 18.99)‡ | 9.151 (2.527, 36.8)‡ |
| INF 3 mg/kg/8 weeks + DMARD | 3.323 (2.086, 5.376)‡ | 3.8 (2.282, 6.521)‡ | 4.361 (2.335, 9.025)‡ |
| RTX 2 × 1000 mg + DMARD | 3.753 (1.761, 8.115)‡ | 4.064 (1.711, 9.807)‡ | 2.563 (0.949, 8.036)‡ |
| TOC 8 mg/kg/4 weeks + DMARD | 4.363 (2.441, 7.89)‡ | 5.797 (3.035, 10.88)‡ | 9.23 (4.318, 20.9)‡ |
Notes:
Results adjusted to 24 weeks of follow-up and standard dose of MTX based on coefficients βweeks and βmtx;
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; the coefficients were not statistically significant except for + (for ACR 70 outcome, longer length of follow-up was associated with higher odds of ACR 70).
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; OR, odds ratio; RTX, rituximab; SUL, sulfasalazine; TOC, tocilizumab.