Background
Methods
Systematic literature search and study selection
Data extraction and outcome assessment
Statistical analysis
Results
Literature search and study characteristics
Study | Treatment arms | Design | Study length (weeks) | Enrolled patients (n) | csDMARD-naïve at baseline (yes, no) | Previous biologic therapy (%) | Mean age (years) | Female (%) | Symptom duration (years) | ESR (mm/h) | CRP (mg/l) | DAS28 | HAQ |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
TCZCOMBI vs. TCZMONO
| |||||||||||||
SURPRISE (2016) | TCZCOMBI
| Open label | 52 | 115 | No | 0 | 56 (12) | 87 | 4 (3) | 41 (28) | 12 (15) | 5.1 (1) | 1.0 (0.7) |
TCZMONO
| 111 | 56 (3) | 87 | 4 (3) | 45 (30) | 18 (26) | 5.3 (1.2) | 1.0 (0.7) | |||||
FUNCTION (2015) | TCZCOMBI
| Double-blind | 52 | 291 | Nof
| 0 | 50 (14) | 79 | 6 (6)g
| 53 (30) | 26 (30) | 6.7 (1.1) | 1.5 (0.6) |
TCZMONO
| 292 | 50 (12) | 75 | 6 (6)g
| 51 (28) | 25 (32) | 6.7(1.0) | 1.6 (0.7) | |||||
ACT-RAY (2013) | TCZCOMBI
| Open-label, double-blindc
| 24 | 277 | No | 0 | 53 (13) | 82 | 8 (8) | NR | NR | 6.3 (1) | 1.5 (0.7) |
TCZMONO
| 276 | 54 (12) | 79 | 8 (8) | 6.4 (1) | 1.5 (0.6) | |||||||
ACT-STAR (2013)a
| TCZCOMBI
| Open-label | 24 | 360 | No | 67 | 54 (12) | 78 | 11 (9) | NR | 14 (21) | 5.5 (1) | NR |
TCZMONO
| 163 | 87 | 54 (13) | 80 | 14 (10) | 19 (33) | 6.0 (1) | ||||||
CHARISMA (2006)b
| TCZCOMBI
| Double-blind | 16 | 50 | No | 14 | 50 (NR) | 78 | 11 (NR)c
| 39 (NR) | 24 (NR) | 6.5 (NR) | NR |
TCZMONO
| 52 | 50 (NR) | 73 | 9 (NR)c
| 39 (NR) | 22 (NR) | 6.4 (NR) | ||||||
TCZCOMBI vs. csDMARD | |||||||||||||
FUNCTION (2015) | TCZCOMBI
| Double-blind | 52 | 291 | No | 0 | 50 (14) | 79 | 6 (6)c
| 53 (30) | 26 (30) | 6.7 (1.1) | 1.5 (0.6) |
csDMARD | 289 | 50 (13) | 80 | 5 (6)c
| 50 (27) | 23 (27) | 6.6 (1.0) | 1.5 (0.7) | |||||
ROSE (2012) | TCZCOMBI
| Double-blind | 24 | 409 | No | 38 | 55 (12) | 80 | 9 (9) | 46 (24) | 17 (21) | 6.5 (1) | 4.1 (1.7)h
|
csDMARD | 205 | 38 | 56 (12) | 84 | 9 (9) | 47 (22) | 17 (22) | 6.6 (1) | 4.0 (2.1)h
| ||||
LITHE (2011)a
| TCZCOMBI
| Double-blindd
| 52 | 398 | No | 11 | 53 (12) | 82 | 9 (NR) | 46 (25) | 23 (26) | 6.6 (1) | 1.5 (0.6) |
csDMARD | 393 | 12 | 51 (12) | 83 | 9 (NR) | 47 (25) | 22 (25) | 6.5 (1) | 1.5 (0.6) | ||||
TOWARD (2008) | TCZCOMBI
| Double-blind | 24 | 803 | No | NS | 53 (13) | 81 | 10 (9) | 48 (28) | 26 (32) | 6.7 (1) | 1.5 (0.6) |
csDMARD | 413 | 54 (13) | 84 | 10 (9) | 49 (28) | 26 (47) | 6.6 (1) | 1.5 (0.6) | |||||
OPTION (2008)a
| TCZCOMBI
| Double-blind | 24 | 205 | No | 5 | 51 (12) | 85 | 8 (7) | 51 (27) | 26 (26) | 6.8 (1) | 1.6 (0.6) |
csDMARD | 204 | 9 | 51 (12) | 78 | 8 (7) | 50 (26) | 24 (28) | 6.8 (1) | 1.5 (0.6) | ||||
RADIATE (2008)a
| TCZCOMBI
| Double-blind | 24 | 170 | No | 100 | 54 (13) | 84 | 13 (9) | 49 (28) | 28 (33) | 6.8 (1) | 1.7 (0.6) |
csDMARD | 158 | 53 (13) | 79 | 11 (9) | 55 (33) | 37 (41) | 6.8 (1) | 1.7 (0.6) | |||||
CHARISMA (2006)b
| TCZCOMBI
| Double-blind | 16 | 50 | No | 14 | 50 (NR) | 78 | 11 (NR)c
| 39 (NR) | 24 (NR) | 6.5 (NR) | NR |
csDMARD | 49 | 51 (NR) | 78 | 11 (NR)c
| 43 (NR) | 32 (NR) | 6.8 (NR) | ||||||
TCZMONO vs. csDMARD | |||||||||||||
FUNCTION (2015) | TCZMONO
| Double-blind | 52 | 292 | No | 0 | 50 (12) | 75 | 6 (6)c
| 51 (28) | 25 (32) | 6.7(1.0) | 1.6 (0.7) |
csDMARD | 289 | 50 (13) | 80 | 5 (6)c
| 50 (27) | 23 (27) | 6.6 (1.0) | 1.5 (0.7) | |||||
AMBITION (2010) | TCZMONO
| Double-blind | 24 | 286 | No | 8 | 51 (13) | 83 | 6 (8) | 50 (28) | 30 (33) | 6.8 (1) | 1.6 (0.7) |
csDMARD | 284 | 7 | 50 (13) | 79 | 6 (8) | 49 (26) | 31 (34) | 6.8 (1) | 1.5 (0.6) | ||||
SATORI (2009) | TCZMONO
| Double-blind | 24 | 61 | No | NS | 53 (11) | 90 | 9 (8) | 52 (28) | 30 (20) | 6.1 (1) | NR |
csDMARD | 64 | 51 (12) | 75 | 9 (7) | 52 (24) | 32 (26) | 6.2 (1) | ||||||
SAMURAI (2007) | TCZMONO
| Open-labele
| 52 | 157 | No | NS | 53 (12) | 80 | 2 (1) | 71 (28) | 47 (29) | 6.5 (1) | NR |
csDMARD | 145 | 53 (13) | 82 | 2 (1) | 71 (25) | 49 (29) | 6.4 (1) | ||||||
CHARISMA (2006)b
| TCZMONO
| Double-blind | 16 | 52 | No | 14 | 50 (NR) | 73 | 9 (NR)c
| 39 (NR) | 22 (NR) | 6.4 (NR) | NR |
csDMARD | 49 | 51 (NR) | 78 | 11 (NR)c
| 43 (NR) | 32 (NR) | 6.8 (NR) |
Efficacy outcomes
DAS28 < 2.6
ACR20 response
ACR50 response
ACR70 response
Safety outcomes
Adverse events
Publication bias
Sensitivity analysis
Meta-analysis | Sensitivity analysesa
| |||||
---|---|---|---|---|---|---|
Outcome measures | RR | 95 % CI |
P
| RR | 95 % CI |
P
|
TCZCOMBI vs. TCZMONO
| ||||||
DAS28 < 2.6 | 1.21 | 1.09, 1.36 | <0.001 | 1.20 | 1.07, 1.34 | 0.002 |
ACR20 | 1.05 | 0.99, 1.12 | 0.11 | 1.05 | 0.98, 1.11 | 0.17 |
ACR50 | 1.14 | 1.03, 1.26 | 0.008 | 1.13 | 1.02, 1.25 | 0.02 |
ACR70 | 1.19 | 0.94, 1.51 | 0.14 | 1.12 | 0.95, 1.33 | 0.19 |
AEs | 1.08 | 0.97, 1.21 | 0.17 | 1.09 | 0.86, 1.38 | 0.48 |
SAEs | 1.40 | 1.03, 1.92 | 0.03 | 1.34 | 0.79, 2.27 | 0.27 |
TCZCOMBI vs. csDMARD | ||||||
DAS28 < 2.6 | 8.77 | 4.10, 18.75 | <0.001 | 10.39 | 4.38, 24.65 | <0.001 |
ACR20 | 2.10 | 1.48, 2.99 | <0.001 | 2.15 | 1.45, 3.19 | <0.001 |
ACR50 | 3.00 | 1.80, 4.99 | <0.001 | 3.24 | 1.82, 5.78 | <0.001 |
ACR70 | 5.32 | 2.31, 12.25 | <0.001 | 6.23 | 2.29, 16.93 | <0.001 |
AEs | 1.12 | 1.06, 1.18 | <0.001 | 1.14 | 1.07, 1.20 | <0.001 |
SAEs | 1.21 | 0.91, 1.60 | 0.19 | 1.13 | 0.80, 1.60 | 0.48 |
TCZMONO vs. csDMARD | ||||||
DAS28 < 2.6 | 3.95 | 2.23, 7.00 | <0.001 | 4.50 | 2.34, 8.64 | <0.001 |
ACR20 | 1.68 | 1.21, 2.32 | 0.002 | 1.71 | 1.18, 2.48 | 0.005 |
ACR50 | 1.87 | 1.19, 2.95 | 0.007 | 2.01 | 1.18, 3.42 | 0.01 |
ACR70 | 2.11 | 1.18, 3.78 | 0.01 | 2.49 | 1.29, 4.81 | 0.007 |
AEs | 1.08 | 1.01, 1.15 | 0.03 | 1.13 | 0.92, 1.39 | 0.24 |
SAEs | 1.21 | 0.87, 1.69 | 0.26 | 1.37 | 0.64, 2.93 | 0.42 |