Table 1.
Prospective controlled studies using methotrexate in Crohn’s disease.
| Indication | Comparator | No. of patients | MTX formulation | MTX dosage (mg/week) | Concomitant steroids (% of patients) | Previous thiopurines | Outcome | |
|---|---|---|---|---|---|---|---|---|
| Feagan et al. 39 | Chronically active CD despite daily dose of at least 12.5 mg of prednisone with at least one attempt to discontinue treatment | Placebo | 141 (MTX = 94; placebo = 47) | i.m. | 25 | 100% | Naive | 16-week clinical remission; 39.4% MTX versus 19.1% placebo (p = 0.025) |
| Oren et al. 41 | Chronic active CD (at least 7.5 mg/day for at least 4 months during the preceding 12 months) | Placebo | 84 (MTX = 26; 6-MP = 32; placebo = 26) | os | 12.5 | 80% (MTX) versus 79% (6-MP) versus 73% (placebo) | 12% (MTX), 27% (6-MP), 15% (placebo). Patients had to be off immunosuppressors for at least 3 months at the time of trial entry | 9-month clinical remission; 39% MTX versus 41% 6-MP versus 46% placebo (p = n.s.) |
| Arora et al. 42 | Steroid-dependent CD | Placebo | 28 (MTX = 13; placebo = 15) | os | 15–22.5 | 26.7% taking at least 20 mg/day prednisone (versus 55.6% in placebo group) | 46.7% (MTX), 22.2% (placebo) | 1-year clinical relapse; 46% MTX versus 80% placebo (p = n.s.) |
| Mate-Jimenez et al. 10 | Steroid-dependent CD | 6-MP 1.5 mg/kg/die, mesalazine 3 g/die | 38 (MTX = 15; 6-MP = 16; placebo = 7) | os | 15 | 100% | Naive | 30-week clinical remission; 93.7% 6-MP versus 80% MTX (p = n.s.) versus 14% 5-ASA (p = 0.01). 76-week remission (in early responders); 53.3% 6-MP versus 66.6% MTX p = n.s.) versus 0% 5-ASA (p < 0.001) |
| Feagan et al. 43 | Chronically active CD despite daily dose of at least 12.5 mg of prednisone with at least one attempt to discontinue treatment | Placebo | 76 (MTX = 40; placebo = 36) responders to MTX 25 mg/week for 16–24 weeks | i.m. | 15 | 0% | 2% | 40-week clinical remission; 65% MTX versus 39% placebo (p = 0.04) |
| Ardizzone et al. 40 | Chronic active CD despite daily dose of at least 10 mg of prednisone with at least one attempt to discontinue treatment | AZA | 54 (MTX = 27; AZA = 27) | i.v. for 3 months, then os for 3 months | 25 | 100% | 15% (MTX), 7% (AZA). Patients had to be off immunosuppressors for at least 3 months at the time of trial entry | 3-month clinical remission; 44% MTX versus 33% AZA (p = n.s.) 6-month clinical remission; 56% MTX versus 63% AZA (p = n.s.) |
Black-coloured cells, negative outcomes; CD, Crohn’s disease; grey-coloured cells, positive outcomes; i.m., intramuscular; i.v., intravenous; MTX, methotrexate; n.s., not significant.