Table 1.
Randomized, Controlled Trials Evaluating MTX for CD or UC.
| Reference and year | MTX dose | Disease | Objective | Severity | No. of patients | Intervention | Duration | Comedication | Outcome |
|---|---|---|---|---|---|---|---|---|---|
| Feagan 1995 [22] | 25 mg/wk parenteral | CD | Induction of remission | Active CD (CDAI > 150) for a minimum of 3 months despite a minimum of 12.5 mg prednisolone | 141 | MTX (n = 94) or placebo (n = 47) | 16 weeks | Steroid to be tapered, mesalazine, steroid enemas, antibiotics (perianal disease) | CDAI < 150 without prednisolone at week 16; MTX superior to placebo (p = 0.025) |
| Arora 1999 [21] | 15–22.5 mg/wk orally | CD | Induction of remission | Steroid-dependent CD | 33 | MTX (n = 15) or placebo (n = 18) | 12 months | Prednisolone ≥10 mg/day | MTX not superior to placebo for induction of remission (p > 0.05) |
| Oren 1997 [25] | 12.5 mg/wk orally | CD | Induction and maintenance of remission | Steroid-dependent CD | 84 | MTX (n = 26) or 6-MP (n = 32) or placebo (n = 26) | 9 months | Steroids and mesalazine | The proportions of patients entering first remission (HBI < 3) or experiencing a relapse (HBI ≥ 3) were without statistically significant differences in the three treatment arms |
| Feagan 2014 [24] | 10–25 mg/wk parenteral | CD | Induction and maintenance of remission (combination of MTX with IFX versus IFX alone) | Active CD initiated on prednisolone induction therapy | 126 | MTX + IFX (n = 63) or IFX + placebo (n = 63) | 50 weeks | IFX; prednisolone to be tapered no later than week 14 | Time to treatment failure (i.e., failure of CDAI < 150 at week 14 or failure to maintain this remission through week 50); MTX was not superior to concomitant treatment with placebo (p = 0.63) |
| Feagan 2000 [23] | 15 mg/wk parenteral | CD | Maintenance of remission | CDAI ≤ 150 at inclusion after previous MTX induction therapy | 76 | MTX (n = 40) or placebo (n = 36) | 40 weeks | Hydrocortisone ointment for perianal disease | Increase in CDAI of more than 100 points or use of rescue medication (steroid/antimetabolite) MTX superior to placebo (p = 0.04) |
| Schröder 2006 [26] |
20 mg/wk perenteral for first 5 weeks then orally | CD | Combination with IFX for induction of remission and maintenance | Active CD resistant or intolerant to thiopurines | 19 | MTX + IFX (n = 11) or IFX (n = 8) | 48 weeks | 5-ASA at doses of 4 g or more, prednisolone 40 mg/day or less (sTable 4 weeks before study entry) | CDAI < 150; time to achieve clinical remission and the corticosteroid tapering effect of treatment; MTX + IFX not superior to IFX at week 48 (p = 0.63) |
| Oren 1996 [28] | 12.5 mg/wk orally | UC | Induction and maintenance of remission | Mayo score ≥ 7 | 67 | MTX (n = 30) or placebo (n = 37) | 9 months | Mesalazine and/or steroids | Proportion entering remission/maintenance of remission, no difference (p > 0.73) |
| Carbonnel 2016 [12] |
25 mg/wk parenteral | UC | Induction of remission | Mayo score 0–12 but steroid dependent | 111 | MTX (n = 60) or placebo (n = 51) | 24 weeks | Steroid to be tapered | Mayo score ≤ 2 at week 16 without steroid; no difference (p = 0.15) |
| Onuk 1996 [27] | 15 mg/wk orally | UC | Maintenance of remission | N/A | 26 | MTX + SASP (n = 14) or MTX (n = 12) | 12 months | Sulfasalazine | Symptoms, sigmoidoscopic and histologic activity; no significant difference (p-value not stated) |
| Herfarth 2018 [13] | 25 mg/wk parenteral | UC | Maintenance of remission | Active UC nonresponding to other therapies treated with MTX open label for 16 weeks | 84 | (Only responders to 16-week induction) to placebo (n = 40) or MTX (n = 44) | 32 weeks MTX | Mesalazine 2.4 g/day | Relapse-free and combined clinical and endoscopic remission; no difference (p = 0.78) |