TABLE 1.
The characteristics of the included studies.
| Source | Mean Age (years) | Disease duration (years) | Baseline DAS28 | Sample Size (Female/Male) | Intervention and dose | Main Outcomes | Age Range | Treatment duration | Disease Stage | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Trial Group | Control Group | Trial Group | Control Group | Trial Group | Control Group | Trial Group | Control Group | ||||||
| Ishiguro N 2015 | 54.8 ± 9.9 | 53.5 ± 10.0 | 4.48 ± 0.83 | 4.48 ± 0.88 | 4.87 ± 0.89 | 4.97 ± 0.86 | 164 (134/30) | 88 (70/18) | IGU 25 mg qd-bid + MTX 6/8 mg qw VS. MTX 6/8 mg qw + PLA | ACR50/70, DAS28, HAQ, RF | 20<years<70 | 24w | - |
| Shi X D 2015 | 48.9 ± 12.2 | 48.4 ± 10.2 | 7.5 ± 4.8 | 7.1 ± 6.6 | 5.2 ± 1.3 | 5.2 ± 1.9 | 30/30 (42/18) | MTX 10–12.5 mg qw + IGU 25 mg bid VS. MTX 10–12.5 mg qw | ACR20/50/70, DAS28, VAS, PGA, EGA, HAQ, SJC, TJC, ESR, CRP, AEs | 22 < years<70 | 24w | First-visit | |
| Bai Q H 2015 | - | - | - | - | - | - | 50/50 (76/24) | IGU 25 mg bid + MTX 10 mg qw VS. MTX 10 mg qw | ACR20/50, AEs | 22 < years<62 | 12w24w | - | |
| Mo H 2015 | 31.8 ± 8.5 | 31.9 ± 8.6 | 5.6 ± 1.8 | 5.5 ± 1.9 | - | - | 30 (22/8) | 30 (21/9) | IGU 25 mg bid + MTX 15 mg qw VS. MTX 15 mg qw | ACR20/50/70, ESR, CRP, RF, Anti-CCP, AEs | 18 < years<72 | 12w | - |
| Xiong Y M 2015 | 56 ± 12 | 51 ± 13 | - | - | - | - | 30 (24/6) | 28 (21/6) | IGU 25 mg bid + MTX 10 mg qw VS. MTX 10 mg qw | DAS28, ESR, CRP, RF, Anti-CCP | 21 < years<68 | 12w,24w | - |
| Xu B J 2015 | 46.10 ± 17.09 | A:43.28 ± 10.46 B:44.71 ± 9.32 | 4.7 ± 0.58 | A:4.34 ± 0.78 B:4.23 ± 0.94 | - | - | 40 (23/17) | A:38 (24/14) B:32 (20/12) | IGU 25 mg bid + MTX 7.5–20 mg qw VS. IGU 25 mg bid VS. MTX 7.5–20 mg qw | PGA, Morning stiffness, TJC, SJC, ESR, CRP, RF, AEs | 23 < years<72 | 52w | - |
| Wang Z J 2016 | 48.71 ± 8.77 | 47.68 ± 7.67 | 8.31 ± 2.61 | 7.28 ± 2.58 | 5.95 ± 1.64 | 6.48 ± 1.92 | 44 (29/15) | 43 (21/6) | IGU 25 mg bid + MTX 15 mg qw VS. MTX 15 mg qw | DAS28, AEs | 35 < years<70 | 24w | Refractory |
| Meng D Q 2016 | 41.6 ± 20.3 | 45.1 ± 19.2 | - | - | 6.40 ± 1.90 | 5.97 ± 1.62 | 30 (26/4) | 30 (23/7) | IGU 25 mg bid + MTX 15 mg qw VS. MTX 15 mg qw | DAS28, AEs | 18 < years<65 | 16w | Refractory |
| Xu L M 2017 | 46.34 ± 2.29 | 46.19 ± 2.57 | - | - | 6.92 ± 2.91 | 6.72 ± 2.94 | 42 (23/19) | 41 (22/19) | IGU 25 mg bid + MTX 7.5–20 mg qw VS. MTX 7.5–20 mg qw | DAS28, Morning stiffness time, ESR, CRP | 21 ≤ year≤70 | 52W | - |
| Cao L N 2018 | 67.5 ± 3.2 | A:68.0 ± 2.8 B:68.5 ± 2.0 | - | - | 4.99 ± 0.17 | A:4.98 ± 0.27 B:4.91 ± 0.30 | 43 (23/19) | A:30 (15/15) B:30 (20/10) | IGU 25 mg bid + MTX 10–12.5 mg qw VS. IGU 25 mg bid VS. MTX 10–12.5 mg qw | DAS28, HAQ | 61 ≤ year≤78 | 24w | - |
| Zhao H N 2018 | 47.20 ± 3.40 | 46.90 ± 3.60 | 4.28 ± 0.36 | 4.23 ± 0.34 | 6.9 ± 2.8 | 6.8 ± 2.9 | 36 (24/12) | 36 (23/13) | MTX 10 mg qw + IGU 25 mg bid VS. MTX 10 mg qw | Morning stiffness, ESR, CRP, AEs | 23 < years<75 | 12w | - |
| Ju Y J 2020 | 42.31 ± 13.78 | 41.87 ± 13.94 | 4.72 ± 0.43 | 4.56 ± 0.58 | 6.46 ± 2.24 | 6.27 ± 2.12 | 58 (23/35) | 58 (25/33) | IGU 25 mg bid + MTX 10–15 mg qw-biw VS. MTX 10–15 mg qw-biw | DAS28, ESR, CRP, RF, AEs | 20.7 < years<69.3 | 24w | Refractory |
| Xiong M L 2020 | 48.21 ± 3.78 | 48.33 ± 5.93 | 1.98 ± 0.43 | 1.54 ± 0.39 | - | - | 51 (29/22) | 51 (30/21) | IGU 25 mg bid + MTX 10–15 mg qw VS. MTX 10–15 mg qw | Morning stiffness, SJC, TJC, AEs | 26 < years<65 | 24w | - |
| Jing J 2020 | 50.03 ± 9.96 | 49.87 ± 9.78 | 6.13 ± 1.53 | 6.26 ± 1.61 | 6.31 ± 0.85 | 6.29 ± 0.83 | 46 (25/21) | 46 (26/20) | IGU 25 mg bid + MTX 10–12.5mg/w VS. MTX 10–12.5mg/w | DAS28, Morning stiffness, ESR, CRP, TJC, SJC, RF | 31 < years<73 | 24w | - |
| Xie L 2018 | 62.89 ± 4.57 | 62.74 ± 3.96 | 6.41 ± 2.16 | 7.35 ± 1.87 | 6.75 ± 1.69 | 6.84 ± 1.87 | 39 (27/12) | 39 (25/14) | IGU 25 mg bid + MTX 10–15 mg qw-biw VS. MTX 10–15 mg qw-biw | DAS28, AEs | 25 < years<71 | 16w | Refractory |
| Qi D X 2019 | - | - | - | - | - | - | 40/40/40 (Unknown) | IGU 25 mg bid + MTX 7.5–10 mg qw VS. IGU 25 mg bid VS. MTX 7.5–10 mg qw | ACR20/50/70, PGA, EGA, HAQ, TCJ, SJC, ESR, CRP, RF, Anti-CCP, AEs | 25<years<65 | 24w | - | |
| Wang L H 2019 | 48.13 ± 6.40 | 47.83 ± 6.37 | 5.60 ± 0.70 | 5.41 ± 0.72 | 6.30 ± 0.88 | 6.27 ± 0.85 | 47 (23/23) | 46 (25/22) | IGU 25 mg bid + MTX 15 mg qw VS. MTX 15 mg qw | DAS28, TJC, SJC, ESR, CRP, RF, AEs | 30 < years<80 | 24w | - |
| Yan K H 2019 | 43.74 ± 4.83 | 43.58 ± 4.6 | 11.54 ± 2.36 | 11.56 ± 2.41 | - | - | 40 (28/12) | 40 (29/11) | IGU 25 mg bid + MTX 15 mg qw VS. MTX 15 mg qw | ACR20/50/70, AEs | 22 < years<69 | 12w/9w | - |
| Zhao W Z 2021 | 48.41 ± 6.39 | 48.36 ± 6.36 | 8.44 ± 2.39 | 8.39 ± 2.36 | 6.28 ± 1.85 | 6.31 ± 1.86 | 52 (26/26) | 52 (28/24) | IGU 25 mg bid + MTX 10 mg qw VS. MTX 10 mg qw | DAS28, Morning stiffness, TJC,SJC,ESR,RF, AEs | 42 < years<55 | 24w | - |
| Duan X 2015 | 48.9 ± 12.2 | 48.4 ± 10.2 | 7.5 ± 4.8 | 7.1 ± 6.6 | 5.2 ± 1.3 | 5.2 ± 0.9 | 30/30 (42/18) | IGU 25 mg bid + MTX 10–12.5 mg qw VS. MTX 10–12.5 mg qw | ACR20/50/70, VAS, PGA, EGA, TJC, SJC, ESR, CRP, AEs | 24w | - | ||
| Xia Z 2016 | 46.63 ± 10.61 | - | - | - | 3.82 ± 0.07 | A:3.98 ± 0.09 B:3.79 ± 0.08 | 44/38/39 (107/24) | IGU 25 mg bid + MTX 10 mg qw VS. IGU 25 mg bid VS. MTX 10 mg qw | Morning stiffness. SJC, TJC, ESR, CRP | 46.63 ± 10.61 | 24w | - | |
| Li S Y 2019 | 45.25 ± 2.78 | 45.425 ± 2.57 | 7.26 ± 0.82 | 7.21 ± 0.80 | - | - | 40 (13/27) | 40 (15/25) | IGU 25 mg bid + MTX 7.5 m g-15 mg qw VS. MTX 7.5 m g-15 mg qw | Morning stiffness, ESR, CRP, AEs | 32 < years<79 | 4w | - |
| Du F 2021 | 48.37 ± 0.69 | A:46.87 ± 0.67 B:47.63 ± 10.70 | 11.67 ± 7.27 | A:11.67 ± 7.16 B:11.60 ± 7.98 | 5.103 ± 0.956 | A:5.084 ± 0.994 B: 5.102 ± 0.979 | 305 (238/67) | A:297 (230/67) B:293 (232/61) | IGU 25 mg bid + MTX 10–15 mg qw VS. IGU 25 mg bid VS. MTX 10–15 mg qw | ACR20,AEs | 52w | First-visit | |
| Chen X Y 2018 | 50.3 ± 6.8 | 7.2 ± 1.5 | - | - | 40/40 (56/24) | IGU 25 mg bid + MTX 10–12.5 mg qw VS. MTX 10–12.5 mg qw | ACR20/50/70, AEs | 31 < years<71 | 4w,8w | - | |||
| Xia Z B 2017 | 54.50 ± 4.50 | 55.25 ± 4.75 | - | - | - | - | 27 (12/15) | 28 (12/16) | IGU 25 mg bid + MTX 10 mg qw-biw VS. MTX 10 mg qw-biw | ESR, CRP, RF | 8w | Refractory | |
| Zhao L 2017 | 45.97 ± 10.75 | A:46.46 ± 11.01 B:46.31 ± 10.89 | - | - | 7.40 ± 0.67 | A: 7.12 ± 0.63 B:7.07 ± 0.50 | 29 (26/3) | A:34 (27/7) B:33 (28/5) | IGU 25 mg bid + MTX 10 mg qw VS. IGU 25 mg bid + PLA 10 mg qw VS. MTX 10 mg qw + PLA 25 mg bid | DAS28-ESR、VAS、PGA、EGA、HAQ、ESR、CRP | 20 < years<69 | 24w | - |
| Chen B X 2021 | 52.73 ± 3.39 | 53.13 ± 3.64 | 9.23 ± 1.52 | 9.94 ± 1.73 | - | - | 30 (18/12) | 30 (20/10) | IGU 25 mg bid + MTX 10 mg qw VS. MTX 10 mg qw + HCQ 200 mg bid | CRP, AEs | 41 < years<70 | 24w | - |
| Liu C L 2020 | 44.4 ± 11.2 | 46.5 ± 12.8 | 8.2 ± 4.1 | 5.7 ± 4.2 | 6.75 ± 2.09 | 6.78 ± 2.13 | 73 (40/33) | 73 (30/43) | IGU 25 mg bid + MTX 10–15 mg qw VS. MTX 10–15 mg qw + HCQ 200 mg bid | DAS28, TJC, SJC, ESR, CRP, RF, AEs | 30 < years<65 | 24w | - |
| Tian X P 2020 | 50 ± 10 | 49 ± 11 | 6.08 ± 6.25 | 6.75 ± 7.33 | - | - | 107 (87/20) | 100 (90/10) | IGU 25 mg bid + MTX 10 mg qw PLA 20 mg qd VS. MTX 10 mg qw + LEF 20 mg qd + PLA 25 mg qd | ACR20/50/70, HAQ, TJC, SJC, ESR, CRP, AEs | 18 < years<70 | 52w | - |
| Zhu L J 2017 | 67.2 ± 3.0 | 66.8 ± 3.1 | 2.7 ± 0.5 | 2.8 ± 0.4 | - | - | 42 (22/20) | 42 (23/19) | IGU 25 mg bid + MTX 10 mg qw VS. LEF 20 mg qd + MTX 10 mg qw | DAS28, Morning stiffness, SJC, TJC, AEs | 67.2 ± 3.0 66.8 ± 3.1 | 24w | First-visit |
| Ma C 2017 | 64.41 ± 6.21 | 6.11 ± 3.41 | 64.22 ± 5.81 | 5.95 ± 3.54 | - | - | 32 (22/10) | 32 (23/9) | IGU 25 mg bid + MTX 10–15 mg qw VS. LEF 20 mg qd + MTX 10–15 mg qw | TJC, SJC, ESR, CRP, AEs | 45 < years<89 | 24w | - |
| Niu M 2021 | 48.16 ± 10.26 | 49.08 ± 11.13 | 6.27 ± 3.21 | 6.57 ± 3.35 | 5.23 ± 0.86 | 5.21 ± 0.79 | 64 (35/29) | 64 (33/31) | IGU 25 mg bid + MTX 10 mg qw VS. LEF 20 mg qd + MTX 10 mg qw | DAS28, VAS, Morning stiffness, TJC, SJC, AEs | 30 < years<65 | 24w | - |
| Meng D Q 2015 | 44.2 ± 20.5 | 41.7 ± 22.8 | - | - | 6.53 ± 1.65 | 6.37 ± 1.89 | 33 (29/4) | 33 (26/7) | IGU 25 mg bid + MTX 10mg/w VS. MTX 10mg/w + LEF 10 mg qd | ACR20/50/70, DAS28, AEs | 44.2 ± 20.5 41.7 ± 22.8 | 8w,16w | Refractory |
| Mo M L 2018 | 45 ± 11.56 | 43.30 ± 10.25 | 0.75 ± 0.58 | 0.82 ± 0.54 | 6.65 ± 1.78 | 6.78 ± 1.55 | 30 (22/8) | 30 (24/6) | IGU 25 mg bid + MTX 10 mg qw VS. MTX 10 mg qw + Tripterygium Glycosides 20 mg tid | DAS28, ESR, CRP, Anti-CCP, RF, AEs | 31 < years<57 | 4w,8w,12w | - |
| Xia N 2020 | 3.73 ± 2.78 | 3.62 ± 2.45 | 4.20 ± 1.41 | 4.17 ± 1.22 | - | - | 50 (39/11) | 50 (37/13) | IGU 25 mg bid + MTX 7.5–15 mg qw VS. MTX 10 mg qw + Tripterygium Glycosides 1–1.5 mg/(kg.d) tid | TJC, SJC, CRP, ESR | 41 < years<68 | 12w | - |
| Li J Y 2021 | 45.32 ± 7.44 | 7.56 ± 8.13 | 4.34 ± 2.19 | 4.12 ± 2.85 | 7.21 ± 1.25 | 7.58 ± 1.63 | 30 (22/8) | 30 (19/11) | IGU 25 mg bid + MTX 10 mg qw VS. MTX 10 mg qw + Tripterygium Glycosides 1–1.5 mg/(kg.d) tid | DAS28, Morning stiffness, SJC, TJC, ESR, CRP, RF, AEs | 45.32 ± 7.44 47.56 ± 8.13 | 24w | Refractory |
| Yang C X 2016 | 45.1 ± 9.1 | 41.9 ± 9.2 | - | - | - | - | 40 (16/24) | 40 (12/28) | IGU 50 qd VS. MTX 10 mg qw | ACR20/50/70 | 39 < years<68 | 12w | - |
| Zhu H 2019 | 46.6 ± 5.9 | 64.4 ± 3.9 | - | - | 5.39 ± 0.70 | 5.46 ± 0.70 | 30 (25/5) | 30 (27/3) | IGU 25 mg bid VS. MTX10 mg qw | ACR20/50/70, AEs | 66.6 ± 5.9 64.4 ± 3.9 | 4w,12w,24w | - |