Key Strategies to Optimize Outcomes in Mild-to-Moderate Ulcerative Colitis
Abstract
:1. Introduction
2. Current Recommendations in Mild-to-Moderate UC
3. Drawbacks and Challenges in Mild-to-Moderate UC Management
4. Key Strategies to Improve the Management of Mild-to-Moderate UC
4.1. 5-ASA Optimization
4.1.1. Once-Daily (OD) Dosing
4.1.2. Combination of Oral and Rectal 5-ASA
4.1.3. Increasing Dose of 5-ASA
4.2. Budesonide MMX Integration in the Therapeutic Armamentarium
4.3. Patient Stratification for Earlier Intervention
4.4. Shared Decision-Making and Patient Involvement
5. A Proposed Algorithm for Practical Guidance
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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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 |
Author (Year) | Study Design | Number of Patients | Study Arms | Primary Outcome | Results | Conclusions |
---|---|---|---|---|---|---|
Sandborn et al. (2012) [63] | RCT | 509 | Budesonide MMX 9 mg Budesonide 6 mg Mesalamine 2.4 g Placebo | Combined clinical and endoscopic remission (UCDAI score ≤1 point, with sub-scores of 0 for both rectal bleeding and stool frequency, no mucosal friability on colonoscopy, and a ≥1-point reduction from baseline in the endoscopic index score) at w 8 | 17.9% (p = 0.0143) 13.2% (p = 0.1393) 12.1% (p = 0.2200) 7.4% | Budesonide MMX 9 mg is safe and more effective than placebo in inducing remission |
Travis et al. (2014) [64] | RCT | 410 | Budesonide MMX 9 mg Budesonide MMX 6 mg Budesonide 9 mg Placebo | Combined clinical and endoscopic remission (UCDAI score ≤1, with a rectal bleeding score of 0, stool frequency score of 0, mucosal appearance score of 0 and a ≥1-point reduction in baseline endoscopic index score) at w 8 | 17.4% (p = 0.0047) 8.3% (p > 0.05) 12.6% (p = 0.0481) 4.5% | Budesonide MMX 9 mg is safe and more effective than placebo in inducing combined clinical and endoscopic remission |
Rubin et al. (2017) [67] | RCT | 510 | Budesonide MMX 9 mg Placebo | Combined clinical and endoscopic remission (UCDAI score of ≤1, with subscale scores of 0 for rectal bleeding, stool frequency, and mucosal appearance) at w 8 | 13.0% (p = 0.049) 7.5% | Budesonide MMX is safe and efficacious for inducing clinical and endoscopic remission for mild-to-moderate UC refractory to oral mesalamine therapy |
Maconi et al. (2019) [69] | Retrospective cohort study | 82 | Budesonide MMX | Clinical remission (pMayo of 0–1 with a rectal bleeding sub-score = 0) at mo. 2 | 50% | Budesonide MMX is safe and effective in patients with mild disease activity |
Danese et al. (2019) [70] | Prospective cohort study | 326 | Cohort 1: budesonide MMX + 5-ASA at least 14 days after increased/optimized 5-ASA dose Cohort 2: budesonide MMX + 5-ASA within 14 days since 5-ASA increased/optimized or without 5-ASA dose modification Cohort 3: budesonide MMX as monotherapy | Clinical benefit (≥3 point reduction UCDAI clinical sub-score) at the end of induction treatment | 64.3% (p = 0.0096) 62.1% 33.3% | Budesonide is safe and well tolerated in about 60% of mild-to-moderate UC patients, in a real-life setting |
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Solitano, V.; D’Amico, F.; Fiorino, G.; Paridaens, K.; Peyrin-Biroulet, L.; Danese, S. Key Strategies to Optimize Outcomes in Mild-to-Moderate Ulcerative Colitis. J. Clin. Med. 2020, 9, 2905. https://doi.org/10.3390/jcm9092905
Solitano V, D’Amico F, Fiorino G, Paridaens K, Peyrin-Biroulet L, Danese S. Key Strategies to Optimize Outcomes in Mild-to-Moderate Ulcerative Colitis. Journal of Clinical Medicine. 2020; 9(9):2905. https://doi.org/10.3390/jcm9092905
Chicago/Turabian StyleSolitano, Virginia, Ferdinando D’Amico, Gionata Fiorino, Kristine Paridaens, Laurent Peyrin-Biroulet, and Silvio Danese. 2020. "Key Strategies to Optimize Outcomes in Mild-to-Moderate Ulcerative Colitis" Journal of Clinical Medicine 9, no. 9: 2905. https://doi.org/10.3390/jcm9092905