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5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

ABSTRACT: BACKGROUND: Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis. METHODS: Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observational studies (case-control and cohort) about the effect of 5-aminosalicylates on the risk of colorectal neoplasia among patients with ulcerative colitis. The Newcastle-Ottawa Scale was used to assess the quality of studies. Adjusted odds ratios (ORs) were extracted from each study. A random-effects model was used to generate pooled ORs and 95% confidence intervals (95%CI). Publication bias and heterogeneity were assessed. RESULTS: Seventeen studies containing 1,508 cases of colorectal neoplasia and a total of 20,193 subjects published from 1994 to 2012 were analyzed. 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis (OR 0.63; 95%CI 0.48-0.84). Pooled OR of a higher average daily dose of 5-aminosalicylates (sulfasalazine ? 2.0 g/d, mesalamine ? 1.2 g/d) was 0.51 [0.35-0.75]. Pooled OR of 5-aminosalicylates use in patients with extensive ulcerative colitis was 1.00 [0.53-1.89]. CONCLUSION: Our pooled results indicated that 5-aminosalicylates use was associated with a reduced risk of colorectal neoplasia in patients with ulcerative colitis, especially in the cases with a higher average daily dose of 5-aminosalicylates use. However, the chemopreventive benefit of 5-aminosalicylates use in patients with extensive ulcerative colitis was limited.

SUBMITTER: Zhao LN

PROVIDER: S-EPMC3978022 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

Zhao Li-Na LN Li Jie-Yao JY Yu Tao T Chen Guang-Cheng GC Yuan Yu-Hong YH Chen Qi-Kui QK

PloS one 20140407 4

<h4>Background</h4>Although the chemopreventive effect of 5-aminosalicylates on patients with ulcerative colitis has been extensively studied, the results remain controversial. This updated review included more recent studies and evaluated the effectiveness of 5-aminosalicylates use on colorectal neoplasia prevention in patients with ulcerative colitis.<h4>Methods</h4>Up to July 2013, we searched Medline, Embase, Web of Science, Cochrane CENTRAL, and SinoMed of China for all relevant observation ...[more]

PMID: 24710620

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Project description:BackgroundWhilst continuation of 5-aminosalicylates (5-ASA) after escalation to biologic therapy is considered ineffective in patients with ulcerative colitis (UC), their role in patients escalated to anti-metabolites is unclear.AimTo compared patterns and outcomes of continuing vs stopping 5-ASA in patients with UC who escalated to anti-metabolite monotherapy, using a de-identified administrative claims database.MethodsWe identified patients with UC who were new users of anti-metabolite monotherapy who were receiving 5-ASA, and were followed for at least 12 months after starting anti-metabolite therapy. We evaluated patterns of 5-ASA use (stopped 5-ASA, short-term 5-ASA use for <6 months after starting anti-metabolites, persistent 5-ASA use for >6 months after starting anti-metabolites). We compared outcomes (risk of UC-related hospitalisation and/or surgery, need for corticosteroids, treatment escalation to biologic therapy) by pattern of 5-ASA use, using Cox proportional hazard analysis adjusting for age, sex, race, comorbidity burden, and hospitalisation or emergency department visit, abdominal surgery and corticosteroid use in the previous 12 months (as measures of disease severity), with a 12-month immortal time period.ResultsOf 4068 patients with UC who were new-users of anti-metabolite monotherapy, 578 (14.2%), 782 (19.2%) and 2708 (66.6%) stopped 5-ASA, used 5-ASA transiently or persistently, respectively. Compared to patients who stopped 5-ASA after starting anti-metabolites, persistent 5-ASA use was associated with a higher risk of UC-related hospitalisation (HR, 1.40 [1.07-1.83]) and corticosteroid use (HR, 1.48 [1.28-1.70]), without an increase in risk of UC-related surgery (HR, 1.32 [0.86-2.00]) or treatment escalation (HR, 0.80 [0.53-1.20]). Sensitivity analyses using a 3 months window after initiation of anti-metabolites to classify patients as continuing vs stopping 5-ASA showed similar results. Residual confounding by disease severity could not be excluded.Conclusion5-ASA are usually continued long-term even after escalating to anti-metabolite therapy in patients with UC without clinical benefit.

Project description:Background & aimsWe compared the efficacy and safety of different first-line (biologic-naïve) and second-line (prior exposure to tumor necrosis factor [TNF] antagonists) agents for treatment of moderate to severely active ulcerative colitis in a systematic review and network meta-analysis.MethodsWe searched publication databases through September 30, 2019, for randomized trials of adults with moderate to severe ulcerative colitis treated with TNF antagonists, vedolizumab, tofacitinib, or ustekinumab, as first-line or second-line agents, compared with placebo or another active agent. Efficacy outcomes were induction and maintenance of remission and endoscopic improvement; safety outcomes were serious adverse events and infections. We performed a fixed-effects network meta-analysis using the frequentist approach, and calculated odds ratios (ORs) and 95% CI values. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Overall quality of evidence was rated using GRADE (Grading of Recommendations, Assessment, Development and Evaluation).ResultsIn biologic-naïve patients, infliximab was ranked highest for induction of clinical remission (OR vs placebo, 4.07; 95% CI, 2.67-6.21; SUCRA, 0.95) and endoscopic improvement (SUCRA, 0.95) (moderate confidence in estimates [CE]). In patients with prior exposure to TNF antagonists, ustekinumab (SUCRA, 0.87) and tofacitinib (SUCRA, 0.87) were ranked highest for induction of clinical remission and were superior to vedolizumab (ustekinumab vs vedolizumab: OR, 5.99; 95% CI, 1.13-31.76 and tofacitinib vs vedolizumab: OR, 6.18; 95% CI, 1.003-8.00; moderate CE) and adalimumab (ustekinumab vs adalimumab: OR, 10.71; 95% CI, 2.01-57.20 and tofacitinib vs adalimumab: OR, 11.05; 95% CI, 1.79-68.41; moderate CE). Vedolizumab had the lowest risk of infections (SUCRA, 0.81), followed by ustekinumab (SUCRA, 0.63) in maintenance trials.ConclusionsIn a systematic review and network meta-analysis, we found infliximab to be ranked highest in biologic-naïve patients, and ustekinumab and tofacitinib were ranked highest in patients with prior exposure to TNF antagonists, for induction of remission and endoscopic improvement in patients with moderate to severe ulcerative colitis. More trials of direct comparisons are needed to inform clinical decision making with greater confidence.

Dataset Information

5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

Publications

5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis.

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