Table 4.
ACR20/50/70 data used in the combination therapy NMA
| Study | Population for sensitivity analysis | Treatment group for analysis | Follow-up (weeks) | Number of patients | ACR 20 n (%) | ACR 50 n (%) | ACR 70 n (%) |
|---|---|---|---|---|---|---|---|
| Abe et al58 | MTX exp; MTX low dose (max 8 mg/wk) | DMARD (MTX) | 14 | 47 | 11 (23.4%) | 4 (8.5%) | 0 (0.0%) |
| INF 3 mg/kg/8 weeks + DMARD (MTX) | 14 | 49 | 30 (61.2%) | 15 (30.6%) | 5 (10.2%) | ||
| INF 10 mg/kg/8 weeks + DMARD (MTX) | 14 | 51 | 27 (52.9%) | 18 (35.3%) | 8 (15.7%) | ||
| Chen et al59 | MTX exp | ADA 40 mg/2 weeks + DMARD (MTX) | 12 | 35 | 19 (54.3%) | 12 (34.3%) | 5 (14.3%) |
| DMARD (MTX) | 12 | 12 | 4 (33.3%) | 2 (16.7%) | 0 (0.0%) | ||
| Combe et al42 | DMARD exp | DMARD (SUL) | 24 | 50 | 14 (28.0%) | 7 (14.0%) | 1 (2.0%) |
| ETN 2 × 25 mg/week | 24 | 103 | 76 (73.8%) | 48 (46.6%) | 22 (21.4%) | ||
| ETN 2 × 25 mg/week + DMARD (SUL) | 24 | 100 | 74 (74.0%) | 52 (52.0%) | 25 (25.0%) | ||
| Durez et al60 | MTX exp | PM 1 mg + DMARD (MTX) | 14 | 15 | 1 (6.7%) | 0 (0.0%) | 0 (0.0%) |
| INF 3 mg/kg/8 weeks + DMARD (MTX) | 14 | 13 | 9 (69.2%) | 6 (46.2%) | 0 (0.0%) | ||
| Edwards et al81 | MTX exp | DMARD (MTX) | 24 | 40 | 15 (37.5%) | 5 (12.5%) | 2 (5.0%) |
| RTX 2 × 1000 mg | 24 | 40 | 26 (65.0%) | 13 (32.5%) | 6 (15.0%) | ||
| RTX 2 × 1000 mg + CYC | 24 | 41 | 31 (75.6%) | 17 (41.5%) | 6 (14.6%) | ||
| RTX 2 × 1000 mg + DMARD (MTX) | 24 | 40 | 29 (72.5%) | 17 (42.5%) | 9 (22.5%) | ||
| Emery et al61 | MTX exp | DMARD (MTX) | 24 | 172 | 40 (23.3%) | 16 (9.3%) | 9 (5.2%) |
| RTX 2 × 500 mg + DMARD (MTX) | 24 | 168 | 92 (54.8%) | 44 (26.2%) | 15 (8.9%) | ||
| RTX 2 × 1000 mg + DMARD (MTX) | 24 | 172 | 87 (50.6%) | 45 (26.2%) | 17 (9.9%) | ||
| Genovese et al48 | MTX exp | ETN 2 × 25 mg/week + DMARD (MTX) | 24 | 80 | 54 (67.5%) | 33 (41.3%) | 17 (21.3%) |
| ETN 1 × 25 mg/week + ANA + DMARD (MTX) | 24 | 81 | 41 (50.6%) | 32 (39.5%) | 19 (23.5%) | ||
| ETN 2 × 25 mg/week + ANA + DMARD (MTX) | 24 | 81 | 50 (61.7%) | 25 (30.9%) | 11 (13.6%) | ||
| Genovese et al43 | DMARD exp; <15% TNF-α exp | TOC 8 mg/kg/4 weeks + DMARD | 24 | 803 | 457 (56.9%) | 282 (35.1%) | 154 (19.2%) |
| DMARD | 24 | 413 | 91 (22.0%) | 33 (8.0%) | 11 (2.7%) | ||
| Huang et al62 | MTX exp | ADA 40 mg/2 weeks + DMARD (MTX) | 24 | 121 | 88 (72.7%) | 49 (40.5%) | 21 (17.4%) |
| ADA 80 mg/2 weeks + DMARD (MTX) | 24 | 121 | 86 (71.1%) | 48 (39.7%) | 21 (17.4%) | ||
| DMARD (MTX) | 24 | 60 | 41 (68.3%) | 26 (43.3%) | 11 (18.3%) | ||
| Kameda et al46 | MTX exp; MTX low dose (max 8 mg/wk) | ETN 2 × 25 mg/week | 24 | 74 | 47 (63.5%) | 35 (47.3%) | 19 (25.7%) |
| ETN 2 × 25 mg/week + DMARD (MTX) | 24 | 77 | 70 (90.9%) | 50 (64.9%) | 30 (39.0%) | ||
| Kay et al63 | MTX exp | DMARD (MTX) | 16 | 35 | 13 (37.1%) | 2 (5.7%) | 0 (0.0%) |
| GOL 50 mg/4 weeks + DMARD (MTX) | 16 | 35 | 21 (60.0%) | 13 (37.1%) | 3 (8.6%) | ||
| GOL 50 mg/2 weeks + DMARD (MTX) | 16 | 34 | 17 (50.0%) | 8 (23.5%) | 5 (14.7%) | ||
| GOL 100 mg/4 weeks + DMARD (MTX) | 16 | 34 | 19 (55.9%) | 10 (29.4%) | 6 (17.6%) | ||
| GOL 100 mg/2 weeks + DMARD (MTX) | 16 | 34 | 27 (79.4%) | 11 (32.4%) | 3 (8.8%) | ||
| Keystone et al64 | MTX exp | ADA 40 mg/2 weeks + DMARD (MTX) | 24 | 207 | 131 (63.3%) | 81 (39.1%) | 43 (20.8%) |
| ADA 20 mg/2 weeks + DMARD (MTX) | 24 | 212 | 129 (60.8%) | 87 (41.0%) | 37 (17.5%) | ||
| DMARD (MTX) | 24 | 200 | 59 (29.5%) | 19 (9.5%) | 5 (2.5%) | ||
| Keystone et al44 | MTX exp;<15% TNF-α exp | DMARD (MTX) | 24 | 199 | 27 (13.6%) | 15 (7.5%) | 6 (3.0%) |
| CZP 200 mg/2 weeks + DMARD (MTX) | 24 | 393 | 231 (58.8%) | 146 (37.2%) | 84 (21.4%) | ||
| CZP 400 mg/2 weeks + DMARD (MTX) | 24 | 390 | 237 (60.8%) | 156 (40.0%) | 80 (20.5%) | ||
| Keystone et al82 | MTX exp | DMARD (MTX) | 24 | 133 | 37 (27.8%) | 18 (13.5%) | 7 (5.3%) |
| GOL 100 mg/4 weeks | 24 | 133 | 47 (35.3%) | 26 (19.5%) | 15 (11.3%) | ||
| GOL 50 mg/4 weeks + DMARD (MTX) | 24 | 89 | 53 (59.6%) | 33 (37.1%) | 18 (20.2%) | ||
| GOL 100 mg/4 weeks + DMARD (MTX) | 24 | 89 | 53 (59.6%) | 29 (32.6%) | 13 (14.6%) | ||
| Kim et al65 | MTX exp | DMARD (MTX) | 24 | 63 | 23 (36.5%) | 9 (14.3%) | 5 (7.9%) |
| ADA 40 mg/2 weeks + DMARD (MTX) | 24 | 65 | 40 (61.5%) | 28 (43.1%) | 14 (21.5%) | ||
| Kremer et al49 | MTX exp;<15% TNF-α exp | DMARD (MTX) | 24 | 119 | 42 (35.3%) | 14 (11.8%) | 2 (1.7%) |
| ABA 2 mg/kg/4 weeks + DMARD (MTX) | 24 | 105 | 44 (41.9%) | 24 (22.9%) | 11 (10.5%) | ||
| ABA 10 mg/kg/4 weeks + DMARD (MTX) | 24 | 115 | 69 (60.0%) | 42 (36.5%) | 19 (16.5%) | ||
| Kremer et al66 | MTX exp | ABA 10 mg/kg/4 weeks + DMARD (MTX) | 24 | 433 | 294 (67.9%) | 173 (40.0%) | 86 (19.9%) |
| DMARD (MTX) | 24 | 219 | 87 (39.7%) | 37 (16.9%) | 14 (6.4%) | ||
| Kremer et al50 | MTX exp;<15% TNF-α exp | DMARD (MTX) | 24 | 129 | 32 (24.8%) | 12 (9.3%) | 4 (3.1%) |
| GOL 2 mg/kg | 24 | 128 | 29 (22.7%) | 11 (8.6%) | 4 (3.1%) | ||
| GOL 4 mg/kg | 24 | 129 | 38 (29.5%) | 15 (11.6%) | 8 (6.2%) | ||
| GOL 2 mg/kg + DMARD (MTX) | 24 | 129 | 48 (37.2%) | 24 (18.6%) | 8 (6.2%) | ||
| GOL 4 mg/kg + DMARD (MTX) | 24 | 128 | 64 (50.0%) | 32 (25.0%) | 10 (7.8%) | ||
| Lan et al67 | MTX exp | ETN 2 × 25 mg/week + DMARD (MTX) | 12 | 29 | 26 (89.7%) | 19 (65.5%) | 7 (24.1%) |
| DMARD (MTX) | 12 | 29 | 10 (34.5%) | 3 (10.3%) | 0 (0.0%) | ||
| Maini et al68 | MTX exp | DMARD (MTX) | 30 | 88 | 18 (20.5%) | 4 (4.5%) | 0 (0.0%) |
| INF 3 mg/kg/8 weeks + DMARD (MTX) | 30 | 86 | 43 (50.0%) | 23 (26.7%) | 7 (8.1%) | ||
| INF 3 mg/kg/4 weeks + DMARD (MTX) | 30 | 86 | 46 (53.5%) | 25 (29.1%) | 9 (10.5%) | ||
| INF 10 mg/kg/8 weeks + DMARD (MTX) | 30 | 87 | 45 (51.7%) | 27 (31.0%) | 16 (18.4%) | ||
| INF 10 mg/kg/4 weeks + DMARD (MTX) | 30 | 81 | 47 (58.0%) | 21 (25.9%) | 9 (11.1%) | ||
| Maini et al51 | MTX exp;<15% TNF-α exp | TOC 2 mg/kg/4 weeks | 16 | 53 | 16 (30.2%) | 3 (5.7%) | 1 (1.9%) |
| TOC 4 mg/kg/4 weeks | 16 | 54 | 33 (61.1%) | 15 (27.8%) | 3 (5.6%) | ||
| TOC 8 mg/kg/4 weeks | 16 | 52 | 33 (63.5%) | 21 (40.4%) | 8 (15.4%) | ||
| TOC 2 mg/kg/4 weeks + DMARD (MTX) | 16 | 52 | 33 (63.5%) | 17 (32.7%) | 7 (13.5%) | ||
| TOC 4 mg/kg/4 weeks + DMARD (MTX) | 16 | 49 | 31 (63.3%) | 18 (36.7%) | 6 (12.2%) | ||
| TOC 8 mg/kg/4 weeks + DMARD (MTX) | 16 | 50 | 37 (74.0%) | 27 (54.0%) | 19 (38.0%) | ||
| DMARD (MTX) | 16 | 49 | 20 (40.8%) | 14 (28.6%) | 8 (16.3%) | ||
| Schiff et al69 | MTX exp | ABA 10 mg/kg/4 weeks + DMARD (MTX) | 28 | 156 | 104 (66.7%) | 63 (40.4%) | 32 (20.5%) |
| DMARD (MTX) | 28 | 110 | 46 (41.8%) | 22 (20.0%) | 10 (9.1%) | ||
| INF 3 mg/kg/8 weeks + DMARD (MTX) | 28 | 165 | 98 (59.4%) | 61 (37.0%) | 40 (24.2%) | ||
| Smolen et al52 | MTX exp;<15% TNF-α exp | TOC 4 mg/kg/4 weeks + DMARD (MTX) | 24 | 214 | 103 (48.1%) | 66 (30.8%) | 26 (12.1%) |
| TOC 8 mg/kg/4 weeks + DMARD (MTX) | 24 | 205 | 121 (59.0%) | 90 (43.9%) | 45 (22.0%) | ||
| DMARD (MTX) | 24 | 204 | 53 (26.0%) | 22 (10.8%) | 4 (2.0%) | ||
| Smolen et al45 | MTX exp;<15% TNF-α exp | DMARD (MTX) | 24 | 127 | 11 (8.7%) | 4 (3.1%) | 1 (0.8%) |
| CZP 200 mg/2 weeks + DMARD (MTX) | 24 | 246 | 141 (57.3%) | 80 (32.5%) | 39 (15.9%) | ||
| CZP 400 mg/2 weeks + DMARD (MTX) | 24 | 246 | 142 (57.7%) | 81 (32.9%) | 26 (10.6%) | ||
| van Riel et al47 | MTX exp | ETN 2 × 25 mg/week | 16 | 160 | 114 (71.3%) | 67 (41.9%) | 28 (17.5%) |
| ETN 2 × 25 mg/week + DMARD (MTX) | 16 | 155 | 104 (67.1%) | 62 (40.0%) | 29 (18.7%) | ||
| Weinblatt et al70 | MTX exp | DMARD (MTX) | 24 | 30 | 8 (26.7%) | 1 (3.3%) | 0 (0.0%) |
| ETN 2 × 25 mg/week + DMARD (MTX) | 24 | 59 | 42 (71.2%) | 23 (39.0%) | 9 (15.3%) | ||
| Weinblatt et al71 | MTX exp | DMARD (MTX) | 24 | 62 | 9 (14.5%) | 5 (8.1%) | 3 (4.8%) |
| ADA 20 mg/2 weeks + DMARD (MTX) | 24 | 69 | 33 (47.8%) | 22 (31.9%) | 7 (10.1%) | ||
| ADA 40 mg/2 weeks + DMARD (MTX) | 24 | 67 | 45 (67.2%) | 37 (55.2%) | 18 (26.9%) | ||
| ADA 80 mg/2 weeks + DMARD (MTX) | 24 | 73 | 48 (65.8%) | 31 (42.5%) | 14 (19.2%) | ||
| Westhovens et al72 | MTX exp | DMARD (MTX) | 22 | 363 | 87 (24.0%) | 33 (9.1%) | 16 (4.4%) |
| INF 3 mg/kg/8 weeks + DMARD (MTX) | 22 | 360 | 199 (55.3%) | 110 (30.6%) | 48 (13.3%) | ||
| INF 10 mg/kg/8 weeks + DMARD (MTX) | 22 | 361 | 205 (56.8%) | 119 (33.0%) | 54 (15.0%) | ||
| Zhang et al53 | MTX exp;<15% TNF-α exp | INF 3 mg/kg/8 weeks + DMARD (MTX) | 14 | 87 | 66 (75.9%) | 38 (43.7%) | 20 (23.0%) |
| DMARD (MTX) | 14 | 86 | 42 (48.8%) | 22 (25.6%) | 12 (14.0%) | ||
| TEMPO (sensitivity analysis only; data from CSR)55 | Mixed naïve and experienced population | DMARD (MTX) | 24 | 228 | 168 (73.7%) | 93 (40.8%) | 35 (15.4%) |
| ETN 2 × 25 mg/week + DMARD (MTX) | 24 | 231 | 189 (81.8%) | 137 (59.3%) | 83 (35.9%) |
Notes: Treatments in bold are treatments of interest (licensed doses); DMARD is the reference treatment.
Abbreviations: ABA, abatacept; ADA, adalimumab; ANA, anakinra; CSR, corporate social responsibility; CYC, cyclophosphate; CZP, certolizumab pegol; DMARD, disease-modifying anti-rheumatic drug; ETN, etanercept; exp, experienced; GOL, golimumab; INF, infliximab; MTX, methotrexate; PM, pulse methylprednisolone; RTX, rituximab; SUL, sulfasalazine; TOC, tocilizumab.