TABLE 2.
Studies on the Efficacy of Methotrexate in UC Patients
| Author | Type of Study | Clinical Type of UC | n | Methotrexate mg/week |
Mode of Application |
Study Length or Period |
Outcome |
|---|---|---|---|---|---|---|---|
| Kozarek 1989 (13) |
Case series | Refractory* | 7 | 25 | IM | 12 weeks | Remission 71% |
| Kozarek 1992 (14) (A) |
Case series | Refractory* | 30 | 25 for 12 weeks then 7.5–15 |
IM (12 weeks) then O |
Median 59 weeks | After 12 weeks 70% response, after 59 weeks 40% remained in remission, 50% colectomy. |
| Baron 1993(15) | Open label study | Steroid dependent | 8 | 15 | O | 18 weeks | Steroid sparing and partial response in 38% |
| Oren 1996(16) | Prospective, placebo controlled |
Moderate acitive; Mayo score ≥ 7 |
30 | 12.5 | O | 9 months | Remission placebo 49%, methotrexate 47%. In this study response not defined as primary or secondary outcome |
| Egan 1999(32) | Randomized, single blind, parallel group comparison (include- ing CD) |
Steroid dependent | 14 | 25 or 15 | P | 16 weeks | Only pooled results for UC (n=14) and CD (n=16) reported: 39% improvement in 15 mg group, 33% improvement in 25 mg group, 17% remission both dose groups. |
| Mate-Jiminez 2000 (54) |
Prospective, open- label either 5-ASA, 6-MP or methotrexate |
Steroid dependent | 12 | 15 | O | 30 weeks | 25% remission on 5-ASA (3 g) 79% remission on 6-MP (1.5 mg/kg.bw) 58% remission on methotrexate |
| Paoluzi 2002 (19) |
Steroid and 6-MP/ azathioprine intolerant or refractory |
10 | 12.5 | IM | 6 months | 100% remission, 60% endoscopic and histologic remission |
|
| Fraser 2002 (20) |
Retrospective, single center (including CD) |
Thiopurine refractory or intolerant |
22 | Mean 20 (range 10–25) |
IM, O | Mean 17.1 months (range 0.5–71) |
Only pooled results for UC (n=22) and CD (n=48) reported: 62% remission after 3 months |
| Fraser 2003 (A) (55) |
Prospective, single center |
Steroid dependent and 6-MP/ azathioprine refractory |
8 | 25 | P | 16 weeks | 25% stopped therapy due to adverse event, 75% completed study without achieving response or remission |
| Sieveke 2003 (56) |
Case series | Not mentioned | 4 | 25 | IM | Not mentioned | 100% remission |
| Soon 2004 (57) | Retrospective, single center (including CD) |
Steroid dependent | 6 | Mean 18 (range 5–30) |
O, IM | 6 months | 100 % steroid sparing, 50% clinical response |
| Cummings 2005 (21) |
Retrospective, single center |
Thiopurine refractory or intolerant or concurrent RA |
50 | 20–25 | O | Median 30 weeks (range: 7–395) |
45% remission, 58% response in thiopurine intolerant 0% remission, 27% response in thiopurine failure 62% remission, 80% response in concomitant RA |
| Rook 2005 (A)(58) |
Retrospective, single center |
Thiopurine intolerant | 8 | 25 for 12 weeks then 15 |
SC for 12 weeks then O |
Mean 10 months (range 4–18) |
75% clinical remission |
| Naik 2007 (A) (59) |
Retrospective, single center |
Thiopurine intolerant or steroid dependent |
54 | 15±6 (O) 18±8 (SC) |
O, SC | > 6 months | 31 patient long term therapy with 84% of these patients benefiting from methotrexate therapy |
| Nathan 2008 (22) |
Retrospective, single center (including CD) |
Thiopurine refractory or intolerant |
23 | Mean 23 (range 15–25) |
SC (90%) O (10%) |
Median 15 months (range 3–37) |
48% remission, 67% response |
| Gonzalez-Lama 2009 (A) (60) |
Retrospective several centers (including CD) |
steroid dependent or steroid resistance |
15 | Mean 15 (range 83–25) |
O, IM, SC | Mean 17 months (range 1–108) |
Only pooled results for UC (n=15) and CD (n=62) reported:82% response, 28% remission. |
| Wahed 2009 (23) |
Retrospective, single center (including CD) |
Thiopurine refractory or intolerant |
32 | Induction Median 25 (range 10–25) Maintenance Median 20 mg (range 10–25) |
O, IM | 6 months | 65% response in thiopurine intolerant 78% response in thiopurine refractory 35% steroid withdrawal |
(A) published as meeting abstract only;
*
no exact definition provided; P, parenteral; O, oral; SC, subcutaneous; IM, intramuscular; bw, bodyweight; RA, rheumatoid arthritis.