Table 1.
Studies reporting the efficacy of different doses and formulations of mesalamine in patients with mild-to-moderate ulcerative colitis.
| Author (Year) | Study Design | Number of Patients | Study Arms | Primary Outcome | Results | Conclusions |
|---|---|---|---|---|---|---|
| Dignass et al. (2009) [41] | Randomized non-inferiority trial | 362 | 5-ASA (2 g) OD 5-ASA (1 g) BD |
1-yr. remission rates (UCDAI score <2) | 70.9% 58.9% (p = 0.024) |
Prolonged-release oral 5-ASA 2 g once daily is associated with better remission rates |
| Flourie et al. (2013) [43] | Randomized non-inferiority trial | 206 | 5-ASA (4 g/day) OD + enema 1 g/day 5-ASA (4 g/day) BD + enema 1 g/day |
Clinical and endoscopic remission at w 8 (UCDAI score <1) | 52.1% 41.8% (p = 0.14) |
Combined with 5-ASA enema, prolonged-release 5-ASA OD 4 g is as effective as 2 g twice daily for inducing remission |
| D’Haens et al. (2017) [44] | Randomized non-inferiority trial | 817 | 5-ASA (3.2 g) OD 5-ASA (3.2 g) BD |
Clinical and endoscopic remission at w 8 (MCS ≤ 2 with no individual score >1) |
22.4% 24.6% (p = 0.005) |
3.2 mg 5-ASA OD is non-inferior to a BD regimen |
| Sandborn et al. (2010) [45] | Randomized non-inferiority trial | 1023 | 5-ASA (1.6–2.4 g/day) OD 5-ASA (1.6–2.4 g/day) BD |
Clinical remission (SCCAI score ≤2 points) at mo. 6 |
90.5% 91.8% (p = 0.05) |
OD dosing of delayed-release 5-ASA is as effective as BD dosing for maintenance of clinical remission |
| Kamm et al. (2007) [46] | RCT | 343 | MMX 5-ASA 2.4 g/day OD MMX 5-ASA 4.8 g/day OD Delayed-release oral 5-ASA 2.4 g/day (3 divided doses) Placebo |
Proportion of patients in clinical and endoscopic remission (modified UCDAI <1 with rectal bleeding and stool frequency scores of 0, no mucosal friability, and a >1-point reduction in sigmoidoscopy score from baseline) at w 8 | 40.5% (p = 0.01) 41.2% (p = 0.007) 32.6% (p = 0.124) 22.1% |
OD MMX 5-ASA 2.4 or 4.8 g/day are both superior to placebo in the induction of clinical and endoscopic remission |
| Lichtenstein et al. (2007) [47] | RCT | 280 | MMX 5-ASA 2.4 g/day BD MMX 5-ASA 4.8 g/day OD Placebo |
Clinical and endoscopic remission (modified UCDAI score <1, with a score of 0 for rectal bleeding and stool frequency, and at least a 1-point reduction in sigmoidoscopy score) at w 8 | 34.1% (p < 0.01) 29.2% 12.9% |
BD and OD MMX 5-ASA are efficacious for the induction of clinical and endoscopic remission |
| Kane et al. (2012) [48] | Phase IV multicentre open label | 290 | MMX 5-ASA 2.4 g/day OD | Clinical recurrence (defined as ≥4 bowel movements per day above the patient’s normal frequency and which were associated with any of the following symptoms: urgency, abdominal pain, or rectal bleeding) at mo. 6 | 23.5% | MMX 5-ASA 2.4 g/day OD is effective for maintaining quiescence |
| D’Albasio et al. (1997) [49] | RCT | 69 | 5-ASA tablets (1.6 g/day) and 5-ASA enemas (4 g/100 mL) twice weekly 5-ASA (1.6 g/day) and placebo enemas/twice weekly |
Maintenance of remission (mild symptoms and normal endoscopic appearance of mucosa) at mo. 12 | 39% 69% (p = 0.036) |
5-ASA given daily by oral route and intermittently by topical route can be more effective than oral therapy alone. |
| Yokoyama et al. (2007) [50] | RCT | 24 | Weekend 5-ASA enema group (1 g 5-ASA enemas in the weekend plus oral 5-ASA 3 g/day for 7 days) Daily oral 5-ASA use only group (only oral 5-ASA 3 g/day for 7 days) |
Incidence of relapse (as a score of ≥6 in clinical activity index and ≥3 in the endoscopic index) | 18.2% 76.9% (multivariate HR: 0.19, 95% CI, 0.04–0.94) |
Adding weekend 1 g 5-ASA enema to daily 3 g oral 5-ASA as maintenance therapy |
| Hanauer et al. (2007) [51] | RCT | 301 | 5-ASA 2.4 g/day 5-ASA 4.8 g/day |
Overall improvement (defined as complete remission or response to therapy) from baseline to w 6 | 57% 72% (p = 0.0384) |
4.8 g/day dose may enhance treatment success rates in patients with moderate disease compared with mesalamine 2.4 g/day |
| Hanauer et al. (2005) [52] | RCT | 386 | 5-ASA 2.4 g/day 5-ASA 4.8 g/day |
Overall improvement (defined as either complete remission or a clinical response to therapy) from baseline to w 6 | 59% 72% (p = 0.036) |
4.8 g/day dose results in significantly higher rates of overall improvement in patients with moderate disease compared with 2.4 g/day |
| Hiwatashi et al. (2011) [53] | RCT | 123 | 5-ASA 4 g/day (2 divided doses) 5-ASA 2.25 g/day (3 divided doses) |
UCDAI score before and after 8 weeks of treatment | 3.0 (95% CI −3.8 to −2.3) 0.8 (95% CI −1.8 to 0.1) |
4 g/day results in a significantly superior change in UCDAI score compared with 2.25 g/day |
| Pica et al. (2015) [54] | RCT | 112 | 5-ASA 4.8 g 5-ASA 2.4 g |
Maintenance of remission (defined as the absence of symptoms and the endoscopically documented absence of the inflammatory changes typical of active UC) at mo. 12 | 75% 64.2% (p = 0.3) |
A daily dose of 4.8 g oral mesalamine results in increased rates and duration of remission compared to 2.4 g, in patients younger than 40 years and/or with extensive disease |
Abbreviations: BD, bis in die (twice daily); MCS, Mayo Clinic Score; HR, hazard ratio; MX, multimatrix system; mo., month; OD, once daily; RCT, randomized controlled trial; SCCAI, Simple Clinical Colitis Activity Index; UC, ulcerative colitis; UCDAI, UC disease activity index; w, week; yr., year; CI, confidence interval.