Table 2.
Meta-analyses of VTE risk in clinical trials of JAK inhibitors for RA and other IMIDs
| Study | JAK inhibitors | No. of study† | JAK inhibitors† | Placebo† | ORs/RRs/RDs (95% CI) * |
Others | ||
|---|---|---|---|---|---|---|---|---|
| Events | Total | Events | Total | |||||
| Xie et al. [64] | Overall | 25 for RA | 12 | 2193 PYs | 3 | 982 PYs | OR 1.16 (0.48–2.81) | (Dose dependency: OR) |
| Tofacitinib | 9 | 1 | 809 PYs | 2 | 205 PYs | OR 0.17 (0.03–1.05) | 5 vs. 10 mg: 0.81 (0.22–3.03) | |
| Baricitinib | 6 | 7 | 693 PYs | 1 | 561 PYs | OR 2.33 (0.62–8.75) | 2 vs. 4 mg: 0.23 (0.02–2.17) | |
| Upadacitinib | 4 | 4 | 285 PYs | 0 | 115 PYs | OR 1.77 (0.20–16.00) | 15 vs. 30 mg: 4.36 (0.47–40) | |
| Filgotinib | 1 | 0 | 178 PYs | 0 | 42 PYs | – | – | |
| Peficitinib | 3 | 0 | 179 PYs | 0 | 42 PYs | – | – | |
| Decernotinib | 2 | 0 | 49 PYs | 0 | 17 PYs | – | – | |
| Xie et al. [65] | Tofacitinib | 12 for RA | 1 | 881 PYs | 2 | 263 PYs | OR 0.06 (0.00–0.95) |
(Dose dependency: OR) 10 vs. 5 mg: 1.47 (0.25–8.50) |
| Yates et al. [66] | Overall | 18 for IMIDs (11 for RA) | 12 (10) | 1950 PYs (1601PYs) | 4 (3) | 709 PYs (625 PYs) | RR 0.68 (0.36–1.29) for IMIDs |
RR 0.44 (0.28–0.70) for PE RR 0.59 (0.31–1.15) for DVT |
| Tofacitinib | 7 (3) | 2 (1) | 1069 (758) | 3 (2) | 122 (77) | – | – | |
| Baricitinib | 2 (2) | 3 (3) | 234 (234) | 0 | 107 (107) | – | – | |
| Upadacitinib | 6 (5) | 6 (6) | 475 (450) | 1 (1) | 378 (352) | – | – | |
| Filgotinib | 3 (1) | 1 (0) | 172 (159) | 0 | 102 (89) | – | – | |
| Olivera et al. [67] | Overall | 10 for IMIDs (6 for RA) | 12 (11) | n = 3740 (2566) | 3 (0) | n = 1403 (997) | RR 0.90 (0.32–2.54) for IMIDs | RR 1.70 (0.48–6.01) for RA |
| Tofacitinib | 4 (2) | 3 (3) | 2060 (1009) | 3 (0) | 536 (254) | – | – | |
| Baricitinib | 1 (1) | 2 (2) | 374 (374) | 0 | 210 (210) | – | – | |
| Upadacitinib | 2 (2) | 5 (5) | 883 (883) | 0 | 385 (385) | – | – | |
| Filgotinib | 3 (1) | 2 (1) | 423 (300) | 0 | 272 (148) | – | – | |
| Bilal et al. [68] | Overall | 25 for IMIDs (14 for RA) | 50 (26) | n = 8933 (6254) | 27 (4) | n = 3612 (2490) | OR 0.91 (0.57–1.47) for IMIDs | OR 1.11 (0.50–2.44) for RA |
| Tofacitinib | 7 (4) | 5 (4) | 3690 (2301) | 5 (2) | 908 (521) | OR 0.27 (0.08–0.89) for IMIDs |
OR 0.54 (0.15–1.96) for 10 mg BID OR 0.49 (0.15–1.55) for 5 mg BID |
|
| Baricitinib | 5 (3) | 9 (7) | 1292 (862) | 1 (1) | 487 (348) | OR 1.12 (0.27–4.69) for IMIDs |
OR 2.69 (0.42‒17.21) for 4 mg QD OR 3.05 (0.12‒75.43) for 2 mg QD |
|
| Upadacitinib | 4 (4) | 12 (12) | 2277 (2277) | 1 (1) | 1256 (1256) | OR 2.25 (0.55–9.25) for IMIDs |
OR2.64 (0.27‒25.45) for 30 mg QD OR2.91 (0.69‒12.21) for 15 mg QD |
|
| Filgotinib | 2 (1) | 2 (1) | 358 (300) | 0 | 206 (148) | OR 2.13 (0.22–20.64) for IMIDs | – | |
| Ruxolitinib | 4 (0) | 19 (0) | 591 (0) | 20 (0) | 482 (0) | OR 0.85 (0.31–2.29) for IMIDs | – | |
| Decernotinib | 2 (2) | 2 (2) | 514 (514) | 0 | 217 (217) | OR 1.07 (0.18–6.43) for IMIDs | – | |
| Abrocitinib | 1 (0) | 1 (0) | 211 (0) | 0 | 56 (0) | OR 0.81 (0.03–20.03) for IMIDs | ‒ | |
| Gimenez Poderos et al. [69] | Tofacitinib | 5 for IMIDs (2 for RA) | – | – | – | – | OR 0.29 (0.10–0.84) for all doses |
OR 1.19 (0.12–11.69) for 3 mg BID OR 0.18 (0.02–1.60) for 5 mg BID OR 0.19 (0.04–0.91) for 10 mg BID OR 0.32 (0.01–8.05) for 15 mg BID |
| Baricitinib | 5 for IMIDs (4 for RA) | – | – | – | – | OR 3.39 (0.82–14.04) for all doses |
OR 3.05 (0.12–75.43) for 2 mg QD OR 3.64 (0.59–22.46) for 4 mg QD OR 3.00 (0.12–76.49) for 7 mg QD |
|
| Khoo et al. [70] ‡ | Overall | 27 for IMIDs (21 for RA) | 12 (10) | n = 8363 (7270) | 3 (3) | n = 3314 (2858) | RD 0.000 (− 0.002–0.003) | – |
| Tofacitinib | 10 (8) | 3 (3) | 4178 (3705) | 2 (2) | 1251 (1095) | 0.000 (− 0.003–0.003) | – | |
| Baricitinib | 7 (6) | 3 (2) | 2176 (1967) | 1 (1) | 1354 (1249) | 0.000 (− 0.003–0.004) | – | |
| Upadacitinib | 2 (2) | 2 (2) | 469 (469) | 0 | 106 (106) | 0.005 (− 0.015–0.024) | – | |
| Filgotinib | 2 (0) | 1 (0) | 123 (0) | 0 | 124 (0) | 0.005 (− 0.020–0.030) | – | |
| Peficitinib | 1 (1) | 0 | 238 (238) | 0 | 51 (51) | 0.000 (− 0.027–0.027) | – | |
| Decernotinib | 2 (1) | 1 (1) | 451(163) | 0 | 112 (41) | 0.001 (− 0.016–0.019) | – | |
| Fostamatinib | 3 (3) | 2 (2) | 728 (728) | 0 | 316 (316) | 0.003 (− 0.006–0.012) | – | |
VTE events included PE and DVT, occurring both individually and in combination
*The ORs, RRs, and RDs of VTE events in patients receiving JAK inhibitors were calculated compared with those receiving placebo
†The numbers in parentheses represent study numbers, PYs, event numbers, or patient numbers for RA patients
‡Only PE events were included
JAK, Janus kinase; RA, rheumatoid arthritis; IMID, immune-mediated inflammatory disease; VTE, venous thromboembolism; PE, pulmonary embolism; DVT, deep vein thrombosis; PYs, person-years; OR, odds ratio; RR, risk ratio; RD, risk difference; 95% CI, 95% confidence interval; BID, twice a day; QD, once a day