Table 2 Summary of subgroup analysis for the safety of voriconazole and other antifungals
Outcome | Subgroup | Variables | No. of studies | No. of patients | OR (95% CI) | I 2% | P | |
|---|---|---|---|---|---|---|---|---|
VRC | counterpart | |||||||
Tolerability | Antifungals | FLU | 2 | 5/218 | 2/197 | 0.86 (0.02, 38.38) | 73 | 0.94 |
AMB | 1 | 19/415 | 23/422 | 0.83 (0.45, 1.55) | NA | 0.56 | ||
ITRA | 3 | 91/330 | 70/311 | 1.42 (0.98, 2.06) | 0 | 0.06 | ||
MCF | 4 | 52/184 | 24/183 | 3.19 [1.77, 5.76] | 0 | 0.0001 | ||
ISA | 1 | 35/259 | 21/257 | 1.76 (0.99, 3.11) | NA | 0.05 | ||
Therapeutic purpose | definitive | 6 | 69/830 | 31/672 | 1.87 [1.20, 2.92] | 0 | 0.005 | |
empirical | 3 | 63/511 | 44/521 | 2.10 (0.72, 6.15) | 80 | 0.18 | ||
prophylaxis | 3 | 87/313 | 71/299 | 1.35 (0.67, 2.69) | 34 | 0.40 | ||
Duration | <14d | 3 | 63/511 | 44/521 | 2.10 (0.72, 6.15) | 80 | 0.18 | |
≥14d | 9 | 156/1143 | 102/971 | 1.54 [1.16, 2.05] | 0 | 0.003 | ||
Neurotoxicity | Antifungals | FLU | 1 | 10/200 | 13/191 | 0.72 [0.31, 1.69] | NA | 0.45 |
AMB | 2 | 20/609 | 3/607 | 6.87 [2.04, 23.16] | 21 | 0.002 | ||
ITRA | 3 | 29/330 | 15/311 | 1.62 [0.84, 3.14] | 52 | 0.15 | ||
MCF | 3 | 13/138 | 0/134 | 10.28 [1.91, 55.44] | 0 | 0.007 | ||
ISA | 1 | 175/259 | 165/257 | 1.16 [0.81, 1.67] | NA | 0.42 | ||
Therapeutic purpose | definitive | 6 | 208/776 | 182/735 | 1.27 [0.93, 1.73] | 26 | 0.13 | |
empirical | 2 | 22/465 | 2/472 | 9.57 [2.57, 35.60] | 0 | 0.0008 | ||
prophylaxis | 2 | 17/295 | 12/293 | 1.40 [0.66, 2.97] | 69 | 0.39 | ||
Duration | ≥14d | 8 | 225/1071 | 194/1028 | 1.29 [0.97, 1.72] | 29 | 0.08 | |
<14d | 2 | 22/465 | 2/472 | 9.57 [2.57, 35.60] | 0 | 0.0008 | ||
Visual toxicity | Antifungals | FLU | 3 | 77/523 | 35/492 | 2.11 [1.38, 3.24] | 66 | 0.0006 |
AMB | 3 | 97/624 | 4/625 | 28.83 [10.84, 76.64] | 75 | <0.00001 | ||
ITRA | 2 | 37/259 | 0/259 | 46.57 [5.89, 368.06] | 0 | 0.0003 | ||
MCF | 3 | 31/138 | 0/134 | 26.63 [5.15, 137.62] | 0 | <0.0001 | ||
ISA | 1 | 69/259 | 39/257 | 2.03 [1.31, 3.15] | NA | 0.002 | ||
Therapeutic purpose | definitive | 8 | 175/1039 | 57/875 | 3.33 [2.41, 4.59] | 49 | <0.00001 | |
empirical | 2 | 103/465 | 2/472 | 53.85 [15.23, 190.37] | 0 | <0.00001 | ||
prophylaxis | 3 | 44/547 | 20/542 | 1.93 [1.11, 3.36] | 68 | 0.02 | ||
Duration | <14d | 11 | 219/1586 | 77/1417 | 2.92 [2.21, 3.85] | 57 | <0.00001 | |
≥14d | 2 | 103/465 | 2/472 | 53.85 [15.23, 190.37] | 0 | <0.00001 | ||
Hepatotoxicity | Antifungals | FLU | 2 | 14/218 | 7/197 | 1.76 (0.71, 4.36) | 0 | 0.22 |
AMB | 3 | 128/624 | 131/625 | 0.99 (0.74, 1.32) | 0 | 0.95 | ||
ITRA | 4 | 46/363 | 21/344 | 2.19 (1.27, 3.76) | 0 | 0.005 | ||
MCF | 3 | 35/138 | 15/134 | 2.78 (1.38, 5.60) | 4 | 0.004 | ||
ISA | 1 | 42/259 | 23/257 | 1.97 (1.15, 3.38) | NA | 0.01 | ||
Therapeutic purpose | definitive | 8 | 156/1039 | 76/875 | 1.79 (1.18, 2.71) | 29 | 0.006 | |
empirical | 2 | 128/465 | 132/472 | 0.98 (0.73, 1.30) | 0 | 0.88 | ||
prophylaxis | 4 | 44/346 | 21/332 | 2.11 (1.22, 3.63)0 | 0 | 0.07 | ||
Duration | <14d | 2 | 128/465 | 132/472 | 0.98 (0.73, 1.30) | 0 | 0.88 | |
≥14d | 11 | 194/1352 | 93/1174 | 1.82 (1.31, 2.54) | 19 | 0.0003 | ||
Nephrotoxicity | Antifungals | FLU | 0 | NA | NA | NA | NA | NA |
AMB | 3 | 45/624 | 110/625 | 0.15 (0.03, 0.84) | 78 | 0.03 | ||
ITRA | 1 | 1/71 | 0/52 | 2.23 (0.09, 55.94) | NA | 0.62 | ||
MCF | 3 | 8/138 | 10/134 | 0.70 (0.25, 1.94) | 0 | 0.49 | ||
ISA | 1 | 58/259 | 55/257 | 1.06 (0.70, 1.61) | NA | 0.79 | ||
Therapeutic purpose | definitive | 6 | 89/804 | 122/666 | 0.36 (0.14, 0.91) | 78 | 0.03 | |
empirical | 2 | 44/465 | 81/472 | 0.50 (0.34, 0.74) | 0 | 0.0006 | ||
prophylaxis | 1 | 1/71 | 0/52 | 2.23 (0.09, 55.94) | NA | 0.62 | ||
Duration | <14d | 2 | 44/465 | 81/472 | 0.50 (0.34, 0.74) | 0 | 0.0006 | |
≥14d | 7 | 90/875 | 122/718 | 0.41 (0.17, 0.98) | 74 | 0.05 | ||