PMID- 32786164 OWN - NLM STAT- MEDLINE DCOM- 20201009 LR - 20231230 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 8 IP - 8 DP - 2020 Aug 12 TI - Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. PG - CD000543 LID - 10.1002/14651858.CD000543.pub5 [doi] LID - CD000543 AB - BACKGROUND: Oral 5-aminosalicylic acid (5-ASA) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. It was previously found that 5-ASA drugs in doses of at least 2 g/day were more effective than placebo but no more effective than SASP for inducing remission in ulcerative colitis (UC). This review is an update of a previously published Cochrane Review. OBJECTIVES: To assess the efficacy, dose-responsiveness and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators (i.e. other formulations of 5-ASA) for induction of remission in active UC. A secondary objective was to compare the efficacy and safety of once-daily dosing of oral 5-ASA versus conventional dosing regimens (two or three times daily). SEARCH METHODS: We searched MEDLINE, Embase and the Cochrane Library on 11 June 2019. We also searched references, conference proceedings and study registers to identify additional studies. SELECTION CRITERIA: We considered randomized controlled trials (RCTs) including adults (aged 18 years or more) with active UC for inclusion. We included studies that compared oral 5-ASA therapy with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily to conventional dosing as well as dose-ranging studies. DATA COLLECTION AND ANALYSIS: Outcomes include failure to induce global/clinical remission, global/clinical improvement, endoscopic remission, endoscopic improvement, adherence, adverse events (AEs), serious adverse events (SAEs), withdrawals due to AEs, and withdrawals or exclusions after entry. We analyzed five comparisons: 5-ASA versus placebo, 5-ASA versus sulfasalazine, once-daily dosing versus conventional dosing, 5-ASA (e.g. MMX mesalamine, Ipocol, Balsalazide, Pentasa, Olsalazine and 5-ASA micropellets) versus comparator 5-ASA (e.g. Asacol, Claversal, Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (95% CI) for each outcome. We analyzed data on an intention-to-treat basis, and used GRADE to assess the overall certainty of the evidence. MAIN RESULTS: We include 54 studies (9612 participants). We rated most studies at low risk of bias. Seventy-one per cent (1107/1550) of 5-ASA participants failed to enter clinical remission compared to 83% (695/837) of placebo participants (RR 0.86, 95% CI 0.82 to 0.89; 2387 participants, 11 studies; high-certainty evidence). We also observed a dose-response trend for 5-ASA. There was no difference in clinical remission rates between 5-ASA and SASP. Fifty-four per cent (150/279) of 5-ASA participants failed to enter remission compared to 58% (144/247) of SASP participants (RR 0.90, 95% CI 0.77 to 1.04; 526 participants, 8 studies; moderate-certainty evidence). There was no difference in remission rates between once-daily dosing and conventional dosing. Sixty per cent (533/881) of once-daily participants failed to enter clinical remission compared to 61% (538/880) of conventionally-dosed participants (RR 0.99, 95% CI 0.93 to 1.06; 1761 participants, 5 studies; high-certainty evidence). Eight per cent (15/179) of participants dosed once daily failed to adhere to their medication regimen compared to 6% (11/179) of conventionally-dosed participants (RR 1.36, 95% CI 0.64 to 2.86; 358 participants, 2 studies; low-certainty evidence). There does not appear to be any difference in efficacy among the various 5-ASA formulations. Fifty per cent (507/1022) of participants in the 5-ASA group failed to enter remission compared to 52% (491/946) of participants in the 5-ASA comparator group (RR 0.94, 95% CI 0.86 to 1.02; 1968 participants, 11 studies; moderate-certainty evidence). There was no evidence of a difference in the incidence of adverse events and serious adverse events between 5-ASA and placebo, once-daily and conventionally-dosed 5-ASA, and 5-ASA and comparator 5-ASA formulation studies. Common adverse events included flatulence, abdominal pain, nausea, diarrhea, headache and worsening UC. SASP was not as well tolerated as 5-ASA. Twenty-nine per cent (118/411) of SASP participants experienced an AE compared to 15% (72/498) of 5-ASA participants (RR 0.48, 95% CI 0.36 to 0.63; 909 participants, 12 studies; moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is high-certainty evidence that 5-ASA is superior to placebo, and moderate-certainty evidence that 5-ASA is not more effective than SASP. Considering relative costs, a clinical advantage to using oral 5-ASA in place of SASP appears unlikely. High-certainty evidence suggests 5-ASA dosed once daily appears to be as efficacious as conventionally-dosed 5-ASA. There may be little or no difference in efficacy or safety among the various 5-ASA formulations. CI - Copyright (c) 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Murray, Alistair AU - Murray A AD - Schulich School of Medicine & Dentistry, University of Western Ontario, London, Canada. FAU - Nguyen, Tran M AU - Nguyen TM AD - Robarts Clinical Trials, London, Canada. FAU - Parker, Claire E AU - Parker CE AD - Robarts Clinical Trials, London, Canada. FAU - Feagan, Brian G AU - Feagan BG AD - Robarts Clinical Trials, London, Canada. AD - Department of Medicine, University of Western Ontario, London, Canada. AD - Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada. FAU - MacDonald, John K AU - MacDonald JK AD - Department of Medicine, University of Western Ontario, London, Canada. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20200812 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Placebos) RN - 3XC8GUZ6CB (Sulfasalazine) RN - 4Q81I59GXC (Mesalamine) SB - IM UOF - Cochrane Database Syst Rev. 2016 Apr 21;4:CD000543. PMID: 27101467 MH - Administration, Oral MH - Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/adverse effects MH - Bias MH - Colitis, Ulcerative/*drug therapy MH - Drug Administration Schedule MH - Humans MH - Induction Chemotherapy/methods MH - Mesalamine/*administration & dosage/adverse effects MH - Patient Dropouts/statistics & numerical data MH - Placebos/therapeutic use MH - Randomized Controlled Trials as Topic MH - Remission Induction MH - Sulfasalazine/*administration & dosage/adverse effects MH - Treatment Failure PMC - PMC8189994 COIS- AM: no known conflicts of interest. TMN: no known conflicts of interest. CEP: no known conflicts of interest. BGF has received fees from Abbott/AbbVie, Amgen, Astra Zeneca, Avaxia Biologics Inc., Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Ferring, JnJ/Janssen, Merck, Nestles, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Takeda, Teva, TiGenix, Tillotts Pharma AG and UCB Pharma for Scientific Advisory Board membership; fees from Abbott/AbbVie, Actogenix, Akros, Albireo Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Avir Pharma, Axcan, Baxter Healthcare Corp., Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma, Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nektar, Nestles, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Protagonist, Receptos, Salix Pharma, Serono, Shire, Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, VHsquared Ltd., Warner-Chilcott, Wyeth, Zealand, and Zyngenia for consultancy; payment for lectures from Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-Chilcott, UCB Pharma; his institution has received grants/grants pending from Abbott/AbbVie, Amgen, Astra Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen, Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts, and UCB Pharma. Dr Feagan was the author of one study that was included in this review. JKM: no known conflicts of interest. EDAT- 2020/08/14 06:00 MHDA- 2020/10/10 06:00 PMCR- 2021/08/12 CRDT- 2020/08/14 06:00 PHST- 2020/08/14 06:00 [entrez] PHST- 2020/08/14 06:00 [pubmed] PHST- 2020/10/10 06:00 [medline] PHST- 2021/08/12 00:00 [pmc-release] AID - CD000543.pub5 [pii] AID - 10.1002/14651858.CD000543.pub5 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2020 Aug 12;8(8):CD000543. doi: 10.1002/14651858.CD000543.pub5.