Plain Language Summary
Introduction
Methods
Search Methodology
Study Selection and Data Extraction
Generic name | Abbreviation | Alternative names | Recommended label dose for RA (FDA unless otherwise stated) |
---|---|---|---|
Abatacept | ABA | Orencia®, bms-188667, CTLA4 ig | Sc 125 mg at week 0, then every week (with or without an iv loading dose) |
Adalimumab | ADA | Humira® | Sc 40 mg every other week (40 mg every week may be considered) |
Anakinra | ANK | Kineret® | Sc 100 mg per day |
Baricitinib | BARI | Olumiant® | EMA: 4 mg once daily |
Certolizumab pegol | CZP | Cimzia®, CDP 870, PHA738144 | Sc 400 mg at weeks 2 and 4, then 200 mg every other week (400 mg every 4 weeks may be considered) |
Etanercept | ETN | Enbrel® | Sc 25 mg twice weekly or 50 mg weekly |
Sarilumab | SRL | Kevzara® | Sc 200 mg once every 2 weeks |
Sirukumaba | SRK | N/A | N/A |
Tocilizumab | TCZ | Actemra®, Atlizumab®, R1569, Roactemra® | Iv 4 mg/kg at week 0, then 8 mg/kg every 4 weeks or sc 162 mg every other week, then every week |
Tofacitinib | TOFA | CP690550, Jakvinus®, tasocitinib, Xeljanz® | Oral 5 mg twice daily |
Risk of Bias Assessment
Compliance with Ethics Guidelines
Results
Literature Search Results
Author | Study name | Patient population | Study phase | Interventions and posologya | Total number of patients | ACR response rates at study endb | Setting | Treatment duration (weeks) | ||
---|---|---|---|---|---|---|---|---|---|---|
ACR20% | ACR50% | ACR70% | ||||||||
Emery et al. [18] | AVERT | MTX-naïve or MTX ≤ 10 mg qw for ≤ 4 weeks, with no MTX ≥ 1 month prior to enrolment | 3b | ABA, sc, 125 mg qw; n = 116 MTX (up to 20 mg qw); n = 116 ABA, sc, 125 mg qw plus MTX (up to 20 mg qw); n = 119 | 351 | ABA: 63.8 MTX: 65.5 ABA-MTX: 74.8 | ABA: 53.4 MTX: 46.6 ABA-MTX: 63.0 | ABA: 38.8 MTX: 34.5 ABA-MTX: 52.1 | Multicenter, multinational | 52 |
Emery et al. [19] (CA) | NR | NR | NR | |||||||
Burmester et al. [20] (CA) | NR | NR | NR | |||||||
Yazici et al. [21] (CA) | NR | NR | NR | |||||||
Furst et al. [22] (CA) | NR | NR | NR | |||||||
Moreland et al. [23] | – | csDMARD-U/I or ETN-U/I | Pilot | PBO, iv; n = 32 ABA, iv, 10 mg/kg; n = 32 | 214 | PBO: 31.6 ABA: 53.3 | PBO: 6.3 ABA: 15.7 | PBO: 0.0 ABA: 6.3 | Multicenter, multinational | 12 |
Breedveld et al. [24] | PREMIER | MTX-naïve | 3 | ADA, sc, 40 mg q2w; n = 274 MTX, oral, up to 20 mg qw; n = 257 ADA, sc, 40 mg q2w plus MTX, oral, up to 20 mg qw; n = 268 | 799 | ADA: 49 MTX: 56 ADA-MTX: 69 P < 0.001 combi vs ADA mono P = 0.002 combi vs MTX mono | ADA: 37 MTX: 43 ADA-MTX: 59 P < 0.001 combi vs either mono | ADA: 28 MTX: 28 ADA-MTX: 47 P < 0.001 combi vs either mono | Multicenter, multinational | 104 |
Miyasaka et al. [25] | CHANGE | csDMARD-U/I | 2/3 | PBO, sc, q2w; n = 87 ADA, sc, 40 mg q2w; n = 91 | 352 | PBO: 13.8 ADA: 44.0 P < 0.001 | PBO: 5.7 ADA: 24.2 P < 0.05 | PBO: 1.1 ADA: 12.1 P < 0.05 | Multicenter (Japan) | 24 |
van de Putte et al. [26] | – | csDMARD-U/I | 3 | PBO, sc, qw; n = 110 ADA, sc, 40 mg qw; n = 103 ADA, sc, 40 mg q2w; n = 113 | 544 | PBO: 19.1 ADA 40 mg qw: 53.4 ADA 40 mg q2w: 46.0 P < 0.001 ADA vs PBO | PBO: 8.2 ADA 40 mg qw: 35.0 ADA 40 mg q2w: 22.1 P < 0.001 ADA qw vs PBO P < 0.05 ADA q2w vs PBO | PBO: 1.8 ADA 40 mg qw: 18.4 ADA 40 mg q2w: 12.4 P < 0.001 ADA qw vs PBO P < 0.05 ADA q2w vs PBO | Multicenter, multinational | 26 |
Fleischmann et al. [27] | – | csDMARD-U/I | 2b | PBO, oral, bid; n = 59 TOFA, oral, 1 mg bid; n = 54 TOFA, oral, 3 mg bid; n = 51 TOFA, oral, 5 mg bid; n = 49 TOFA, oral, 10 mg bid; n = 61 TOFA, oral, 15 mg bid; n = 57 ADA, sc, 40 mg q2w, BL-10 weeks then TOFA, oral, 5 mg, 12–24 weeks; n = 53 | 384 | NR | NR | NR | Multicenter, multinational | 24 |
Popa et al. [28] | – | DMARD-experienced | 1 | PBO; n = 13 ADA; n = 33 (dose information not available) | 46 | NR | NR | NR | Single center | 2 |
Gabay et al. [29] | ADACTA | MTX-U/I | 4 | ADA, sc, 40 mg q2w; n = 163 TCZ, iv, 8 mg/kg q4w; n = 163 | 326 | ADA: 49.4 TCZ: 65.0 P = 0.004 | ADA: 27.8 TCZ: 47.2 P < 0.001 | ADA: 17.9 TCZ: 32.5 P = 0.002 | Multicenter, multinational | 24 |
Strand et al. [30] (CA) | NR | NR | NR | NR | NR | NR | ||||
Burmester et al. [31] (CA) | MONARCH | MTX-U/I | 3 | ADA, sc, 40 mg q2w; n = 185 SRL, sc, 200 mg q2w; n = 184 | 369 | ADA: 58.4 SRL: 71.7 P = 0.007 | ADA: 29.7 SRL: 45.7 P = 0.002 | ADA: 11.9 SRL: 23.4 P = 0.004 | Multicenter, multinational | 24 |
Burmester et al. [32] | NR | NR | NR | |||||||
Taylor et al. [33] (CA) | SIRROUND-H | MTX-U/I MTX-naïve | 3 | ADA, sc, 40 mg q2w; n = 186 SRK, sc, 50 mg q4w; n = 186 SRK, sc, 100 mg q2w; n = 187 | 559 | ADA: 56.5 SRK 50 mg: 53.8 SRK 100 mg: 58.8 | ADA: 31.7 SRK 50 mg: 26.9 SRK 100 mg: 35.3 | NR | Global | 24 |
Fleischmann et al. [34] (CA) | RA-BEGIN | csDMARD-naïve (≤ 3 weekly MTX doses permitted) | 3 | BARI, 4 mg qd; n = 159 MTX, up to 20 mg qw; n = 210 BARI, 4 mg qd plus MTX up to 20 mg qw; n =215 | 584 | BARI: 77 MTX: 62 BARI-MTX: 78 | BARI: 60 MTX: 43 BARI-MTX: 63 | BARI: 42 MTX: 21 BARI-MTX: 40 | Multicenter, multinational | 24 |
P ≤ 0.01 BARI vs MTX | P ≤ 0.01 BARI vs MTX | P ≤ 0.001 BARI/combi vs MTX | ||||||||
P ≤ 0.001 combi vs MTX | P ≤ 0.001 combi vs MTX | |||||||||
Fleischmann et al. [35] | NR | NR | NR | 52 | ||||||
Weinblatt et al. [36] | REALISTIC | csDMARD-U/I | 3b | PBO, sc, q2w; n = 212 CZP 200 mg, sc, q2w (following initial dosing of 400 mg) with or without MTX; n = 851 | 1063 | PBO: 25.9 CZP: 51.1 P < 0.001 | PBO: 9.9 CZP: 26.6 P < 0.001 | PBO: 2.8 CZP: 12.9 P < 0.001 | Multicenter, multinational | 12 |
Yamamoto et al. [37] | HIKARI | MTX-U/I | 3 | PBO, q2w; n = 114 CZP 200 mg, q2w (following initial dosing at weeks 0, 2, 4 with 400 mg) ± non-MTX DMARD; n = 116 | 230 | NR | NR | NR | Japan | 24 |
Fleischmann et al. [38] | FAST4WARD | csDMARD-U/I | 3 | PBO, sc, q4w; n = 109 CZP, sc, 400 mg q4w; n = 111 | 220 | PBO: 9.3 CZP: 45.5 P < 0.001 | PBO: 3.7 CZP: 22.7 P < 0.001 | PBO: 0.0 CZP: 5.5 P < 0.05 | Multicenter, multinational | 24 |
Johnsen et al. [39] | – | csDMARD-U/I | NR | ETN, sc, 25 mg bw; n = 26 | 77 | ETN: 65 | ETN: 38 | ETN: 15 | Multicenter (USA) | 24 |
Combe et al. [40] | – | SSZ-U/I | NR | ETN, sc, 25 mg bw; n = 103 SSZ (2, 2.5, or 3 g qd); n =50 ETN, sc, 25 mg bw plus SSZ (2, 2.5, 3 g qd); n = 101 | 254 | ETN: 73.8 SSZ: 28.0 ENT-SSZ: 74 P < 0.05 SSZ vs combi or ETN | ETN: 46.6 SSZ: 14.0 ETN-SSZ: 52.0 P < 0.05 SSZ vs combi or ETN | ETN: 21.4 SSZ: 2.0 ETN-SSZ: 25.0 P < 0.05 SSZ vs combi or ETN | Multicenter | 24 |
Combe et al. [41] | ETN: 67.0 SSZ: 33.7 ETN-SSZ: 77.2 P < 0.01 SSZ vs combi P < 0.05 SSZ vs ETN | ETN: 46.8 SSZ: 10.3 ETN-SSZ: 58.7 P < 0.01 SSZ vs combi P < 0.05 SSZ vs ETN | ETN: 24.4 SSZ: 2.0 ETN-SSZ: 28.1 P < 0.01 SSZ vs combi P < 0.05 SSZ vs ETN | 104 | ||||||
Kameda et al. [42] (CA) | JESMR | MTX-U/I | 4 | ETN, sc, 25 mg bw; n = 74 ETN, sc, 25 mg bw plus MTX (6–8 mg qw); n = 77 | 151 | NR | NR | NR | Multicenter (Japan) | 104 |
Kameda et al. [43] | ETN: 63.8 ETN-MTX: 90.4 P < 0.001 | ETN: 47.8 ETN-MTX: 64.4 | ETN: 26.1 ETN-MTX: 38.4 | 24 | ||||||
Klareskog et al. [44] | TEMPO | csDMARD-U/I | 3 | ETN, sc, 25 mg bw; n = 223 MTX, oral, up to 20 mg qw; n = 228 ETN, sc, 25 mg bw plus MTX, oral, up to 20 mg qw; n = 231 | 682 | ETN: 76 MTX: 75 ETN-MTX: 85 P = 0.009 combi vs MTX P = 0.015 combi vs ETN | ETN: 48 MTX: 43 ETN-MTX: 63 P < 0.001 combi vs MTX or ETN | ETN: 24 MTX: 19 ETN-MTX: 43 P < 0.001 combi vs MTX or ETN | Multicenter (multinational) | 52 |
van der Heijde et al. [45] | ETN: 75 MTX: 71 ETN-MTX: 86 P < 0.01 combi vs MTX or ETN | ETN: 54 MTX: 42 ETN-MTX: 71 P < 0.01 combi vs MTX or ETN | ETN: 27 MTX: 21 ETN-MTX: 49 P < 0.01 combi vs MTX or ETN | 104 | ||||||
van der Heijde et al. [46] | ETN: 70.9 MTX: 70.2 ETN-MTX: 85.3 P < 0.01 combi vs MTX or ETN | ETN: 45.7 MTX: 43.9 ETN-MTX: 67.1 P < 0.01 combi vs MTX or ETN | ETN: 26.0 MTX: 21.1 ETN-MTX: 47.2 P < 0.01 combi vs MTX or ETN | 156 | ||||||
Moreland et al. [47] | – | csDMARD-U/I | 3 | PBO, sc, bw; n = 80 ETN, sc, 25 mg bw; n = 78 | 234 | PBO: 11 ETN: 59 P < 0.001 | PBO: 5 ETN: 40 P < 0.001 | PBO: 1 ETN: 15 P < 0.031 | Multicenter (North America) | 26 |
Mathias et al. [48] | NR | NR | NR | |||||||
Bathon et al. [49] | ENBREL ERA | MTX-naïve | NR | ETN, sc, 25 mg bw; n = 207 MTX, oral, 7.5 mg qw; n = 217 | 632 | ETN: 72 MTX: 65 | NR | NR | NR | 52 |
Hu et al. [50] | – | csDMARD-experienced | NR | ETN, sc, 25 mg bw; n = 118 MTX, oral, up to 15 mg qw; n = 120 | 238 | ETN: 75.4 MTX: 70.0 | ETN: 40.7 MTX: 30.8 | ETN: 20.3 MTX: 10.8 P = 0.042 | Multicenter (China) | 24 |
Takeuchi et al. [51] | – | csDMARD-U/I | 3 | ETN, sc, 25 mg bw; n = 182 MTX, oral, 6–8 mg qw; n = 176 | 550 | ETN: 78.6 MTX: 62.5 P < 0.001 | ETN: 62.1 MTX: 36.9 P < 0.001 | ETN: 36.3 MTX: 15.9 P < 0.001 | Multicenter (Japan) | 52 |
Genovese et al. [52] | – | MTX-U/I | NR | ETN, sc, 25 mg bw; n = 80 ETN, sc, 25 mg bw plus ANK, 100 mg, qd; n = 81 | 242 | ETN: 68 ETN-ANK: 62 P = 0.037 | ETN: 41 ETN-ANK: 31 | ETN: 21 ETN-ANK: 14 | Multicenter (USA) | 24 |
Weinblatt et al. [53] | – | csDMARD-experienced | 2 | ETN, sc, 25 mg bw; n = 36 ETN, sc, 25 mg bw plus ABA, iv, 2 mg/kg; n = 85 | 121 | NR | NR | NR | Multicenter (USA) | 156 |
Burmester et al. [31] (CA) | MONARCH | MTX-U/I | 3 | ADA, sc, 40 mg q2w; n = 185 SRL, sc, 200 mg q2w; n = 184 | 369 | ADA: 58.4 SRL: 71.7 P = 0.007 | ADA: 29.7 SRL: 45.7 P = 0.002 | ADA: 11.9 SRL: 23.4 P = 0.004 | Multicenter, multinational | 24 |
Burmester et al. [32] | ADA: 58.4 SRL: 71.7 P ≤ 0.007 | ADA: 29.7 SRL: 45.7 P ≤ 0.007 | ADA: 11.9 SRL: 23.4 P ≤ 0.007 | |||||||
Takeuchi et al. [54] (CA) | – | NR | NR | SRK, 50 mg q4w; n = 56 SRK, 100 mg q2w; n = 58 | 122 | NR | NR | NR | Japan | 52 |
Takeuchi et al. [55] (CA) | SIRROUND-D | csDMARD-U/I | 3 | PBO, sc, q2w; n = 556 SRK, sc, 50 mg q4w; n =557 SRK, sc, 100 mg q2w; n = 557 | 1670 | NR | NR | NR | Global | 52 |
Aletaha et al. [56] | SIRROUND-T | csDMARD-U/I csDMARD-naïve | 3 | PBO, sc, q2w; n = 294 SRK, sc, 50 mg q4w; n =292 SRK, sc, 100 mg q2w; n = 292 | 878 | PBO: 26 SRK 50 mg q4w: 43 SRK 100 mg q2w: 43 P < 0.001 SRK vs PBO | PBO: 9 SRK 50 mg q4w: 21 SRK 100 mg q2w: 22 P < 0.001 SRK vs PBO | PBO: 4 SRK 50 mg q4w: 9 SRK 100 mg q2w: 10 P = 0.026 SRK 100 mg q2w vs PBO P = 0.006 SRK 50 mg q4w vs PBO | Global | 24 |
Taylor et al. [33] (CA) | SIRROUND-H | MTX-U/I MTX-naïve | 3 | ADA, sc, 40 mg q2w; n = 186 SRK, sc, 50 mg q4w; n =186 SRK, sc, 100 mg q2w; n = 187 | 559 | ADA: 56.5 SRK 50 mg q4w: 53.8 SRK 100 mg q2w: 58.8 | ADA: 31.7 SRK 50 mg q4w: 26.9 SRK 100 mg q2w: 35.3 | NR | Global | 24 |
Burmester et al. [57] (CA) | FUNCTION | MTX-naïve | 3 | TCZ, iv, 8 mg/kg q4w; n = 292 MTX, up to 7.5–20 mg qw; n = 289 TCZ, iv, 8 mg/kg q4w plus MTX, up to 20 mg qw; n = 291 | 1162 | NR | NR | NR | NR | 52 |
Burmester et al. [58] (CA) | TCZ: 61.6 MTX: 25.4 TCZ-MTX: 65.2 | TCZ: 53.1 MTX: 22.0 TCZ-MTX: 57.6 | TCZ: 39.4 MTX: 17.4 TCZ-MTX: 46.6 | 104 | ||||||
Burmester et al. [59] | TCZ: 62.7 MTX: 56.7 TCZ-MTX: 66.8 P = 0.012 MTX vs combi | TCZ: 49.1 MTX: 40.7 TCZ-MTX: 55.6 P < 0.001 MTX vs combi P = 0.036 MTX vs TCZ | TCZ: 35.8 MTX: 28.8 TCZ-MTX: 42.8 P < 0.001 MTX vs combi | 52 | ||||||
Burmester et al. [60] (CA) | FUNCTION AMBITION | MTX-naïve | 3 | TCZ, iv, 8 mg/kg; n = 408 MTX, oral; n = 412 | 820 | FUNCTION MTX: 65.2 TCZ: 70.2 AMBITION MTX: 60.0 TCZ: 73.3 | FUNCTION MTX: 43.2 TCZ: 47.6 AMBITION MTX: 40.8 TCZ: 53.4 | FUNCTION MTX: 25.4 TCZ: 30.1 AMBITION MTX: 19.2 TCZ: 35.3 | NR | 24 |
Weinblatt et al. [61] | ACT-STAR | csDMARD-U/I | 3b | TCZ, iv, 8 mg/kg q4w; n = 163 TCZ, iv, 8 mg/kg q4w, plus csDMARD; n = 360 | 886 | TCZ: 40.5 TCZ-DMARD: 38.0 | TCZ: 16.4 TCZ-DMARD: 12.0 | TCZ: 4.8 TCZ-DMARD: 4.1 | Multicenter (USA) | 24 |
Takeuchi et al. [62] (CA) | SURPRISE | MTX-U/I | NR | TCZ switch, iv, 8 mg/kg q4w; n = 115 MTX, 15 mg qw, plus TCZ add-on, iv, 8 mg/kg q4w; n = 118 | 233 | TCZ: 66.7 TCZ-MTX: 64.3 | TCZ: 53.2 TCZ-MTX: 48.7 | TCZ: 36.0 TCZ-MTX: 27.8 | Multicenter (Japan) | 24 |
Dougados et al. [63] | ACT-RAY | MTX-experienced | NR | TCZ switch, iv, 8 mg/kg q4w; n = 277 MTX, 15 mg qw, plus TCZ add-on, iv, 8 mg/kg q4w; n = 279 | 556 | TCZ: 70.3 TCZ-MTX: 71.5 | TCZ: 40.2 TCZ-MTX: 45.5 | TCZ: 25.4 TCZ-MTX: 24.5 | Multicenter | 24 |
Herold et al. [64] (CA) | OPTIMISE | MTX-U/I | NR | TCZ, iv, 8 mg/kg q4w; n = 33 TCZ, iv, 8 mg/kg q4w plus MTX, sc, 15–25 mg qw; n = 30 | 65 | NR | NR | NR | Austria | 24 |
Pablos et al. [65] (CA) | – | csDMARD-U/I | 3 | TCZ, iv, 8 mg/kg q4w; n = 82 TCZ, iv, 8 mg/kg q4w plus MTX, oral; n = 83 | 165 | NR | NR | NR | NR | 44 |
Nishimoto et al. [66] | STREAM | csDMARD-U/I | 2 | PBO, iv, q4w; n = 53 TCZ, iv, 8 mg/kg q4w; n = 55 | 162 | PBO: 11.3 TCZ: 78.2 P < 0.001 | PBO: 1.9 TCZ: 40.0 P < 0.001 | PBO: 0.0 TCZ: 16.4 P = 0.002 | Multicenter (Japan) | 12 |
Ogata et al. [67] | MUSASHI | csDMARD-U/I | 3 | TCZ, iv, 8 mg/kg q4w; n = 173 TCZ, sc, 162 mg q2w; n = 173 | 346 | TCZ iv: 86.0 TCZ sc: 79.2 | NR | NR | Multicenter (Japan) | 24 |
Ogata et al. [68] | TCZ iv: 84.5 TCZ sc: 76.2 | TCZ iv: 61.8 TCZ sc: 57.7 | TCZ iv: 37.7 TCZ sc: 34.9 | |||||||
Ogata et al. [69] (CA) | – | NR | NR | TCZ, sc, 162 mg qw; n = 21 TCZ, sc, 162 mg q2w; n = 21 | 42 | TCZ qw: 52.4 TCZ q2w: 20.0 | TCZ qw: 38.1 TCZ q2w: 15.0 | TCZ qw: 14.3 TCW q2w: 15.0 | Japan | 12 |
Durez et al. [70] | TOMERA | MTX-naïve | NR | TCZ, iv, 8 mg/kg q4w; n = 17 MTX, 20 mg/wk; n = 13 | 30 | NR | NR | NR | NR | 76 |
Jones et al. [71] | AMBITION | Not MTX-U/I | NR | TCZ, iv, 8 mg/kg q4w; n = 288 MTX, sc, up to 20 mg qw; n = 284 | 673 | TCZ: 69.9 MTX: 52.6 | TCZ: 44.1 MTX: 33.5 | TCZ: 28.0 MTX: 15.0 | Multicenter (multinational) | 24 |
Nishimoto et al. [72] | SAMURAI | csDMARD-U/I | NR | TCZ, iv, 8 mg/kg q4w; n = 157 csDMARD therapy; n = 145 | 302 | TCZ: 78 csDMARD: 34 P < 0.001 | TCZ: 64 csDMARD: 13 P < 0.001 | TCZ: 44 csDMARD: 6 P < 0.001 | Multicenter (Japan) | 52 |
Kawashiri et al. [73] | TCZ, iv, 8 mg/kg q4w; n = 9 csDMARD therapy; n = 10 | 19 | NR | NR | NR | 12 | ||||
Nishimoto et al. [74] | SATORI | MTX-U/I | NR | TCZ, iv, 8 mg/kg q4w; n = 61 MTX, sc, 8 mg qw; n = 64 | 125 | TCZ: 84.1 MTX: 35.1 | TCZ: 54.0 MTX: 15.9 | TCZ: 32.2 MTX: 10.9 | Multicenter (Japan) | 24 |
Gabay et al. [29] | ADACTA | MTX-U/I | 4 | ADA, sc, 40 mg q2w; n = 163 TCZ, iv, 8 mg/kg q4w; n = 163 | 326 | ADA: 49.4 TCZ: 65.0 P = 0.004 | ADA: 27.8 TCZ: 47.2 P < 0.001 | ADA: 17.9 TCZ: 32.5 P = 0.002 | Multicenter, multinational | 24 |
Strand et al. [30] (CA) | AMBITION ADACTA | MTX-naïve (AMBITION) MTX-U/I (ADACTA) | NR | TCZ, iv, 8 mg/kg q4w; n = 265 MTX, sc, up to 20 mg qw; n = 259 (AMBITION) ADA, sc, 40 mg q2w; n = 162 TCZ, iv, 8 mg/kg q4w; n = 163 (ADACTA) | NR | NR | NR | NR | NR | 24 |
Fleischmann et al. [75] | ORAL SOLO | DMARD-U/I | 3 | PBO, 13 weeks then TOFA, oral 5 mg bid for 13 weeks; n = 61 PBO, 13 weeks then TOFA, oral 10 mg bid for 13 weeks; n = 61 TOFA, oral 5 mg qd for 26 weeks; n = 243 TOFA, oral 10 mg qd for 26 weeks; n = 245 | 610 | PBO → TOFA 5 mg: 60 TOFA 5 mg: 68 | NR | NR | Multicenter, multinational | 26 |
Strand et al. [76] | NR | NR | NR | |||||||
Tanaka et al. [77] (CA) | – | csDMARD-U/I | 2b | PBO, oral, bid; n = 52 TOFA, oral, 1 mg bid; n = 53 TOFA, oral, 3 mg bid; n = 53 TOFA, oral, 5 mg bid; n = 52 TOFA, oral, 10 mg bid; n = 53 TOFA, oral, 15 mg bid; n = 54 | 317 | PBO: 15.4 TOFA 5 mg: 73.1 P < 0.001 | PBO: 7.7 TOFA 5 mg: 46.2 P < 0.001 | PBO: 1.9 TOFA 5 mg: 26.9 P < 0.05 | Japan | 12 |
Tanaka et al. [78] | 2 | PBO: 15.4 TOFA 5 mg: 73.1 P < 0.001 | PBO: 7.8 TOFA 5 mg: 45.6 P < 0.05 | PBO: 2.4 TOFA 5 mg: 26.7 P < 0.05 | ||||||
Kremer et al. [79] | – | MTX-U/I | 2a | PBO, bid; n = 65 TOFA, oral, 5 mg bid; n = 61 TOFA, oral, 15 mg bid; n = 69 TOFA, oral, 30 mg bid; n = 69 | 264 | PBO: 29.2 TOFA 5 mg: 70.5 P < 0.001 | PBO: 6.2 TOFA 5 mg: 33.0 P < 0.001 | PBO: 3.1 TOFA 5 mg: 13.3 P < 0.05 | Multicenter, multinational | 6 |
Fleischmann et al. [80] (CA) | ORAL START | MTX-naïve | 3 | TOFA, oral, 5 mg bid; n = 373 TOFA, oral, 10 mg bid; n = 397 MTX, 10–20 mg qw; n = 186 | 956 | NR | TOFA 5 mg: 50 MTX: 32 | TOFA 5 mg: 28 MTX: 15 | Multicenter, multinational | 24 |
Fleischmann et al. [81] (CA) | NR | TOFA 5 mg: 50 MTX: 32 | TOFA 5 mg: 28 MTX: 15 | 24 | ||||||
Lee et al. [82] (CA) | TOFA: 71.0 MTX: 50.5 P < 0.001 | TOFA: 46.6 MTX: 27.2 P < 0.001 | TOFA: 25.5 MTX: 12.0 P < 0.001 | 52 | ||||||
Fleischmann et al. [83] (CA) | Early RA TOFA: 68.9 MTX: 47.2 Established RA TOFA: 58.2 MTX: 36.8 All P < 0.05 | Early RA TOFA: 54.1 MTX: 32.1 Established RA TOFA: 42.9 MTX: 23.7 All P < 0.05 | Early RA TOFA: 40.8 MTX: 15.1 Established RA TOFA: 26.5 MTX: 15.8 All P < 0.05 | 104 | ||||||
Fleischmann et al. [84] | Early RA TOFA: 68.8 MTX: 47.3 P < 0.001 Established RA TOFA: 58.2 MTX: 36.8 P < 0.01 | Early RA TOFA: 54.0 MTX: 32.0 P < 0.001 Established RA TOFA: 43.0 MTX: 23.5 P < 0.01 | Early RA TOFA: 40.9 MTX: 15.0 P < 0.001 Established RA TOFA: 26.5 MTX: 15.8 P < 0.05 | 104 | ||||||
Alten et al. [85] (CA) | NR | NR | NR | 104 | ||||||
Strand et al. [86] | NR | NR | NR | 104 | ||||||
Strand et al. [87] (CA) | NR | NR | NR | 104 | ||||||
Charles-Schoeman et al. [88] (CA) | TOFA 5 mg +GC: 65.2 TOFA 5 mg –GC: 62.7 MTX +GC: 49.4 MTX –GC: 37.1 P < 0.05 TOFA vs MTX within subgroup | TOFA 5 mg +GC: 50.8 TOFA 5 mg –GC: 47.0 MTX +GC: 31.8 MTX –GC: 25.8 P < 0.05 TOFA vs MTX within subgroup | TOFA 5 mg +GC: 34.3 TOFA 5 mg –GC: 34.1 MTX +GC: 14.1 MTX –GC: 16.5 P < 0.05 TOFA vs MTX within subgroup | 104 | ||||||
Fleischmann et al. [27] | – | csDMARD-U/I | 2b | PBO, oral, bid; n = 59 TOFA, oral, 1 mg bid; n = 54 TOFA, oral, 3 mg bid; n = 51 TOFA, oral, 5 mg bid; n = 49 TOFA, oral, 10 mg bid; n = 61 TOFA, oral, 15 mg bid; n = 57 ADA, sc, 40 mg q2w, BL-10 weeks then TOFA, oral, 5 mg, 12–24 weeks; n = 53 | 384 | PBO: 25.4 TOFA 5 mg: 51.0 P ≤ 0.05 | PBO: 10.2 TOFA 5 mg: 34.7 P ≤ 0.05 | PBO: 6.8 TOFA 5 mg: 20.4 P ≤ 0.05 | Multicenter, multinational | 24 |