Table 3.
Incidence of MTX discontinuation (MTX-D) due to liver injury in IBD and non-IBD patients.
| IBD | Non-IBD | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Groups | No. of articles | Cumulative incidence | 95% CI | No. of articles | Cumulative incidence | 95% CI | RR | 95% CI of RR | P of RR |
| Total | 39 | 2.6% | 1.8- 3.6% | 139 | 1.8% | 1.3–2.3% | 1.48 | 0.94–2.33 | 0.089 |
| Subgroup: Year of publication, before 2000 | 9 | 2.8% | 1.1–5.1% | 30 | 3.2% | 1.8–5% | 0.86 | 0.34–2.21 | 0.76 |
| Subgroup: Year of publication, after 2000 | 30 | 2.7% | 1.7–3.8% | 109 | 1.5% | 1.1–2% | 1.76 | 1.05–2.94 | 0.031 |
| Subgroup: Region of study, North America | 13 | 3.1% | 1.7–4.6% | 41 | 1.2% | 0.5–2.1% | 2.52 | 1.09–5.81 | 0.03 |
| Subgroup: Region of study, Europe | 21 | 2.7% | 1.5–4.2% | 57 | 3.2% | 2.2–4.3% | 0.85 | 0.46–1.58 | 0.609 |
| Subgroup: Study design, prospective | 10 | 2.1% | 0.7–4.2% | 95 | 1.5% | 1–2.1% | 1.39 | 0.51–3.75 | 0.516 |
| Subgroup: Study design, retrospective | 29 | 2.8% | 1.8–3.9% | 44 | 2.3% | 1.4–3.5% | 1.2 | 0.66–2.2 | 0.548 |
| Subgroup: Children | 10 | 2.7% | 1.6–4.1% | 5 | 2.1% | 0–6.8% | 1.29 | 0.05–34.85 | 0.881 |
| Subgroup: Adult | 29 | 2.6% | 1.5–3.9% | 134 | 1.8% | 1.3–2.3% | 1.48 | 0.86–2.56 | 0.159 |
| Subgroup: Sample size, ≤ 100 | 35 | 2.5% | 1.5–3.7% | 66 | 2.4% | 1.3–3.9% | 1.04 | 0.52–2.1 | 0.911 |
| Subgroup: Sample size, >100 | 4 | NAa | NA | 73 | 1.6% | 1.1–2.1% | NA | NA | NA |
| Subgroup: Administration of MTX, intramuscularly | 9 | 1.9% | 0.4–4% | 5 | 1.1% | 0.2–2.5% | 1.67 | 0.31–9 | 0.55 |
| Subgroup: Administration of MTX, orally | 8 | 2.8% | 1.6–4.2% | 68 | 2.5% | 1.7–3.6% | 1.08 | 0.58–2.03 | 0.8 |
| Subgroup: Administration of MTX, subcutaneously | 8 | 1.9% | 0.6–3.7% | 4 | NA | NA | NA | NA | NA |
| Subgroup: Administration of MTX, combination | 11 | 4.1% | 1.9–6.9% | 14 | 1.5% | 0.4–3.2% | 2.68 | 0.76–9.45 | 0.13 |
| Subgroup: Dose of MTX, low | 13 | 3.1% | 1.8–4.7% | 95 | 1.7% | 1.1–2.3% | 1.83 | 0.99–3.36 | 0.052 |
| Subgroup: Dose of MTX, high | 26 | 2.4% | 1.3–3.6% | 38 | 1.5% | 0.8–2.4% | 1.56 | 0.75–3.25 | 0.231 |
| Subgroup: Duration of MTX, short term | 34 | 2.5% | 1.7–3.4% | 115 | 1.8% | 1.3–2.4% | 1.38 | 0.86–2.24 | 0.186 |
| Subgroup: Duration of MTX, long term | 5 | 4.1% | 0.5–9.9% | 22 | 1.4% | 0.5–2.6% | 2.89 | 0.55–15.23 | 0.21 |
| Subgroup: Usage of steroid, Yes | 30 | 2.7% | 1.8–3.8% | 34 | 0.7% | 0.2–1.2% | 4.09 | 1.66–10.08 | 0.002 |
| Subgroup: Usage of folic acid, Yes | 21 | 3% | 1.9–4.2% | 64 | 1.9% | 1.3–2.7% | 1.53 | 0.89–2.65 | 0.127 |
| Subgroup: Steroid + low dose + short term | 9 | 3.3% | 1.8–5.2% | 21 | 0.8% | 0.2–1.7% | 4.24 | 1.12–16.13 | 0.034 |
| Subgroup: Steroid + high dose/long term | 21 | 2.5% | 1.4–3.9% | 11 | 0.5% | 0–1.3% | 5.16 | 0.74–36.14 | 0.098 |
| Subgroup: Folic acid + low dose + short term | 6 | 3.9% | 1.9–6.5% | 32 | 2.3% | 1.3–3.6% | 1.7 | 0.77–3.75 | 0.19 |
| Subgroup: Folic acid + high dose/long term | 15 | 2.6% | 1.4–4.1% | 30 | 1.2% | 0.6–2% | 2.12 | 0.95–4.75 | 0.067 |
| Subgroup: Steroid/folic acid + low dose/short term | 10 | 3.3% | 1.9–5% | 44 | 1.8% | 1–2.7% | 1.84 | 0.91–3.69 | 0.087 |
| Subgroup: Steroid/folic acid + high dose/long term | 24 | 2.7% | 1.6–4% | 38 | 1.1% | 0.6–1.7% | 2.52 | 1.24–5.11 | 0.01 |
a
NA indicates that analysis is not performed due to limited number of articles (<5).
MTX, methotrexate; IBD, inflammatory bowel disease; CI, confidence interval; RR, relative risk.