Abstract
Pharmacotherapy is the cornerstone of management in ulcerative colitis. However, controversy remains over optimal medical strategies. Specifically, differences in the onset of action of various drug therapies are thought to influence the achievement and maintenance of remission of disease, yet this is poorly characterised.
There is a wide range of recent data concerning aminosalicylates, with much debate as to the relative merits of the various formulations and delivery systems. Meta-analyses confirm the efficacy of aminosalicylates for the induction and maintenance of remission and suggest that the newer agents are comparable in efficacy to sulfasalazine. Among aminosalicylates, data from clinical trials reveal that the onset of action is earlier with balsalazide than mesalazine. Although the efficacy of the newer 5-aminosalicylate agents is no greater than that of sulfasalazine, they have better adverse effect profiles. Factors such as tolerability and adherence appear more important than onset of action in long-term maintenance.
Corticosteroids have long been used in the treatment of ulcerative colitis, yet there is a paucity of data regarding this. They have a rapid onset of action but considerable systemic adverse effects. Therefore, corticosteroids are reserved for disease that fails to respond to other agents or for primary therapy in patients with severe disease, although there is no universal acceptance of a threshold at which to initiate corticosteroid treatment.
Rectal preparations of both aminosalicylates and corticosteroids have been developed in an attempt to exert a more rapid and direct onset of action while minimising adverse systemic effects. In clinical trials, topical preparations of both aminosalicylates and corticosteroids are effective in inducing remission. However, patient acceptability and proximal extent of disease dictate selection of a topical agent more than concern with rate of onset.
A wide range of immunomodulators have been investigated in patients with steroid-refractory ulcerative colitis. The thioguanine derivatives are the most widely used but have a limited evidence base to support this use with controlled trials providing equivocal results regarding efficacy in severe ulcerative colitis. In addition, the thioguanine derivatives have a protracted onset of action and a considerable serious adverse effect profile. Calcineurin inhibitors and methotrexate have a more rapid onset of action than the thiopurines but have even less data to support their widespread use. They are widely regarded as salvage therapy and further data are required. Regarding biological agents, infliximab revolutionised the treatment of Crohn’s disease, yet results in ulcerative colitis have been disappointing. Further trials are ongoing with great anticipation for more favourable data.
The practical clinical implications of any differences between the agents depend on patient satisfaction with various therapies. Noncompliance is a major concern in maintenance therapy and is probably associated with relapse. Dose administration schedules and acceptability of therapy appear to be important factors in adherence. Overall, it is not clear that onset of action has a major influence on patient adherence and addressing issues of compliance may have more direct clinical impact.
Similar content being viewed by others
Notes
The use of trade names is for product identification purposes only and does not imply endorsement.
References
Hanauer SB. Medical therapy for ulcerative colitis 2004. Gastroenterology 2004 May; 126(6): 1582–92
Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults. Gut 2004 Sep; 53 Suppl. 5: V1–16
Sutherland L, Roth D, Beck P, et al. Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2002; (4): CD000544
Sutherland L, MacDonald JK. Oral 5-aminosalicylic acid for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2003; (3): CD000543
Svartz N. Salazopyrin, a new sulfanilamide preparation. Acta Med Scand 1942; 110: 557–90
Baron JH, Connell AM, Lennard-Jones JE, et al. Sulphasalazine and salicylazosulphadimidine in ulcerative colitis. Lancet 1962 May; I: 1094–6
Goldman P, Peppercorn MA. Drug therapy: sulfasalazine. N Engl J Med 1975 Jul; 293(1): 20–3
Toovey S, Hudson E, Hendry WF, et al. Sulphasalazine and male infertility: reversibility and possible mechanism. Gut 1981 Jun; 22(6): 445–51
Birnie GG, McLeod TI, Watkinson G. Incidence of sulphasalazine-induced male infertility. Gut 1981 Jun; 22(6): 452–5
Azad Khan AK, Piris J, Truelove SC. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 1977 Oct; II(8044): 892–5
Klotz U, Maier K, Fischer C, et al. Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn’s disease. N Engl J Med 1980 Dec; 303(26): 1499–502
Das KM, Eastwood MA, McManus JP, et al. The metabolism of salicylazosulphapyridine in ulcerative colitis: I. The relationship between metabolites and the response to treatment in inpatients. Gut 1973 Aug; 14(8): 631–41
Das KM, Eastwood MA, McManus JP, et al. Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med 1973 Sep; 289(10): 491–5
Doering J, Begue B, Lentze MJ, et al. Induction of T lymphocyte apoptosis by sulphasalazine in patients with Crohn’s disease. Gut 2004 Nov; 53(11): 1632–8
Prakash A, Markham A. Oral delayed-release mesalazine: a review of its use in ulcerative colitis and Crohn’s disease. Drugs 1999 Mar; 57(3): 383–408
Travis SP, Jewell DP. Salicylates for ulcerative colitis: their mode of action. Pharmacol Ther 1994 Aug; 63(2): 135–61
Egan LJ, Mays DC, Huntoon CJ, et al. Inhibition of interleukin-1-stimulated NF-kappaB RelA/p65 phosphorylation by mesalamine is accompanied by decreased transcriptional activity. J Biol Chem 1999 Sep; 274(37): 26448–53
Bantel H, Berg C, Vieth M, et al. Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol 2000 Dec; 95(12): 3452–7
Sandborn WJ, Hanauer SB. Systematic review: the pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in the management of ulcerative colitis. Aliment Pharmacol Ther 2003 Jan; 17(1): 29–42
Feurle GE, Theuer D, Velasco S, et al. Olsalazine versus placebo in the treatment of mild to moderate ulcerative colitis: a randomised double blind trial. Gut 1989 Oct; 30(10): 1354–61
Hanauer S, Schwartz J, Robinson M, et al. Mesalamine capsules for treatment of active ulcerative colitis: results of a controlled trial. Pentasa Study Group. Am J Gastroenterol 1993 Aug; 88(8): 1188–97
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis: a randomized study. N Engl J Med 1987 Dec; 317(26): 1625–9
Sninsky CA, Cort DH, Shanahan F, et al. Oral mesalamine (Asacol) for mildly to moderately active ulcerative colitis: a multicenter study. Ann Intern Med 1991 Sep; 115(5): 350–5
Zinberg J, Molinas S, Das KM. Double-blind placebo-controlled study of olsalazine in the treatment of ulcerative colitis. Am J Gastroenterol 1990 May; 85(5): 562–6
Green JR, Mansfield JC, Gibson JA, et al. A double-blind comparison of balsalazide, 6.75g daily, and sulfasalazine, 3g daily, in patients with newly diagnosed or relapsed active ulcerative colitis. Aliment Pharmacol Ther 2002 Jan; 16(1): 61–8
Mansfield JC, Giaffer MH, Cann PA, et al. A double-blind comparison of balsalazide, 6.75g, and sulfasalazine, 3g, as sole therapy in the management of ulcerative colitis. Aliment Pharmacol Ther 2002 Jan; 16(1): 69–77
Fleig WE, Laudage G, Sommer H, et al. Prospective, randomized, double-blind comparison of benzalazine and sulfasalazine in the treatment of active ulcerative colitis. Digestion 1988; 40(3): 173–80
Rachmilewitz D. Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ 1989 Jan; 298(6666): 82–6
Munakata A, Yoshida Y, Muto T, et al. Double-blind comparative study of sulfasalazine and controlled-release mesalazine tablets in the treatment of active ulcerative colitis. J Gastroenterol 1995 Nov; 30 Suppl. 8: 108–11
Rao SS, Dundas SA, Holdsworth CD, et al. Olsalazine or sulphasalazine in first attacks of ulcerative colitis? A double blind study. Gut 1989 May; 30(5): 675–9
Willoughby CP, Cowan RE, Gould SR, et al. Double-blind comparison of olsalazine and sulphasalazine in active ulcerative colitis. Scand J Gastroenterol Suppl 1988; 148: 40–4
Green JR, Lobo AJ, Holdsworth CD, et al. Balsalazide is more effective and better tolerated than mesalamine in the treatment of acute ulcerative colitis: the Abacus Investigator Group. Gastroenterology 1998 Jan; 114(1): 15–22
Levine DS, Riff DS, Pruitt R, et al. A randomized, double blind, dose-response comparison of balsalazide (6.75g), balsalazide (2.25g), and mesalamine (2.4g) in the treatment of active, mild-to-moderate ulcerative colitis. Am J Gastroenterol 2002 Jun; 97(6): 1398–407
Pruitt R, Hanson J, Safdi M, et al. Balsalazide is superior to mesalamine in the time to improvement of signs and symptoms of acute mild-to-moderate ulcerative colitis. Am J Gastroenterol 2002 Dec; 97(12): 3078–86
Miner P, Hanauer S, Robinson M, et al. Safety and efficacy of controlled-release mesalamine for maintenance of remission in ulcerative colitis: Pentasa UC Maintenance Study Group. Dig Dis Sci 1995 Feb; 40(2): 296–304
Hawkey CJ, Dube LM, Rountree LV, et al. A trial of zileuton versus mesalazine or placebo in the maintenance of remission of ulcerative colitis: the European Zileuton Study Group For Ulcerative Colitis. Gastroenterology 1997 Mar; 112(3): 718–24
Wright JP, O’Keefe EA, Cuming L, et al. Olsalazine in maintenance of clinical remission in patients with ulcerative colitis. Dig Dis Sci 1993 Oct; 38(10): 1837–42
Ardizzone S, Petrillo M, Molteni P, et al. Coated oral 5-aminosalicylic acid (Claversal) is equivalent to sulfasalazine for remission maintenance in ulcerative colitis: a double-blind study. J Clin Gastroenterol 1995 Dec; 21(4): 287–9
Riley SA, Mani V, Goodman MJ, et al. Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology 1988 Jun; 94(6): 1383–9
Ireland A, Mason CH, Jewell DP. Controlled trial comparing olsalazine and sulphasalazine for the maintenance treatment of ulcerative colitis. Gut 1988 Jun; 29(6): 835–7
Kiilerich S, Ladefoged K, Rannem T, et al. Prophylactic effects of olsalazine v sulphasalazine during 12 months maintenance treatment of ulcerative colitis: the Danish Olsalazine Study Group. Gut 1992 Feb; 33(2): 252–5
Kruis W, Judmaier G, Kayasseh L, et al. Double-blind dose-finding study of olsalazine versus sulphasalazine as maintenance therapy for ulcerative colitis. Eur J Gastroenterol Hepatol 1995 May; 7(5): 391–6
McIntyre PB, Rodrigues CA, Lennard-Jones JE, et al. Balsalazide in the maintenance treatment of patients with ulcerative colitis, a double-blind comparison with sulphasalazine. Aliment Pharmacol Ther 1988 Jun; 2(3): 237–43
Mulder CJ, Tytgat GN, Weterman IT, et al. Double-blind comparison of slow-release 5-aminosalicylate and sulfasalazine in remission maintenance in ulcerative colitis. Gastroenterology 1988 Dec; 95(6): 1449–53
Nilsson A, Danielsson A, Lofberg R, et al. Olsalazine versus sulphasalazine for relapse prevention in ulcerative colitis: a multicenter study. Am J Gastroenterol 1995 Mar; 90(3): 381–7
Rijk MC, van Lier HJ, van Tongeren JH. Relapse-preventing effect and safety of sulfasalazine and olsalazine in patients with ulcerative colitis in remission: a prospective, double-blind, randomized multicenter study. The Ulcerative Colitis Multicenter Study Group. Am J Gastroenterol 1992 Apr; 87(4): 438–42
Rutgeerts P. Comparative efficacy of coated, oral 5-aminosalicylic acid (Claversal) and sulphasalazine for maintaining remission of ulcerative colitis. International Study Group. Aliment Pharmacol Ther 1989 Apr; 3(2): 183–91
Dick AP, Grayson MJ, Carpenter RG, et al. Controlled trial of sulphasalazine in the treatment of ulcerative colitis. Gut 1964 Oct; 50: 437–42
Giaffer MH, O’Brien CJ, Holdsworth CD. Clinical tolerance to three 5-aminosalicylic acid releasing preparations in patients with inflammatory bowel disease intolerant or allergic to sulphasalazine. Aliment Pharmacol Ther 1992 Feb; 6(1): 51–9
Kruis W, Schreiber S, Theuer D, et al. Low dose balsalazide (1.5g twice daily) and mesalazine (0.5g three times daily) maintained remission of ulcerative colitis but high dose balsalazide (3.0g twice daily) was superior in preventing relapses. Gut 2001 Dec; 49(6): 783–9
Rembacken BJ, Snelling AM, Hawkey PM, et al. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 1999 Aug; 354(9179): 635–9
Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut 2004 Nov; 53(11): 1617–23
Faubion WA, Sandborn WJ. Probiotic therapy with E. coli for ulcerative colitis: take the good with the bad. Gastroenterology 2000 Mar; 118(3): 630–1
Franchimont D, Kino T, Galon J, et al. Glucocorticoids and inflammation revisited: the state of the art. NIH Clinical Staff Conference. Neuroimmunomodulation 2003; 10(5): 247–60
Kusunoki M, Moeslein G, Shoji Y, et al. Steroid complications in patients with ulcerative colitis. Dis Colon Rectum 1992 Oct; 35(10): 1003–9
Truelove SC, Witts LJ. Cortisone in ulcerative colitis: final report on a therapeutic trial. BMJ 1955 Oct; (4947): 1041–8
Lennard-Jones JE, Longmore AJ, Newell AC, et al. An assessment of prednisone, salazopyrin, and topical hydrocortisone hemisuccinate used as out-patient treatment for ulcerative colitis. Gut 1960 Sep; 1: 217–22
Truelove SC, Watkinson G, Draper G. Comparison of corticosteroid and sulphasalazine therapy in ulcerative colitis. BMJ 1962 Dec; 5321: 1708–11
Baron JH, Connell AM, Kanaghinis TG, et al. Out-patient treatment of ulcerative colitis: comparison between three doses of oral prednisone. BMJ 1962 Aug; 5302: 441–3
Faubion Jr WA, Loftus Jr EV, Harmsen WS, et al. The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology 2001 Aug; 121(2): 255–60
Lofberg R, Danielsson A, Suhr O, et al. Oral budesonide versus prednisolone in patients with active extensive and left-sided ulcerative colitis. Gastroenterology 1996 Jun; 110(6): 1713–8
Angus P, Snook JA, Reid M, et al. Oral fluticasone propionate in active distal ulcerative colitis. Gut 1992 May; 33(5): 711–4
Hawthorne AB, Record CO, Holdsworth CD, et al. Double blind trial of oral fluticasone propionate v prednisolone in the treatment of active ulcerative colitis. Gut 1993 Jan; 34(1): 125–8
Campieri M, Adamo S, Valpiani D, et al. Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis: a multicentre randomised study. Aliment Pharmacol Ther 2003 Jun; 17(12): 1471–80
Rizzello F, Gionchetti P, D’Arienzo A, et al. Oral beclometasone dipropionate in the treatment of active ulcerative colitis: a double-blind placebo-controlled study. Aliment Pharmacol Ther 2002 Jun; 16(6): 1109–16
Friend DR. Review article: issues in oral administration of locally acting glucocorticosteroids for treatment of inflammatory bowel disease. Aliment Pharmacol Ther 1998 Jul; 12(7): 591–603
Bjorck S, Dahlstrom A, Ahlman H. Topical treatment of ulcerative proctitis with lidocaine. Scand J Gastroenterol 1989 Nov; 24(9): 1061–72
Connell AM, Lennard-Jones JE, Misiewicz JJ, et al. Comparison of acetarsol and prednisolone-21-phosphate suppositories in the treatment of idiopathic proctitis. Lancet 1965 Jan; 191: 238
Lennard-Jones JE, Baron JH, Connell AM, et al. A double blind controlled trial of prednisolone-21-phosphate suppositories in the treatment of idiopathic proctitis. Gut 1962 Sep; 3: 207–10
Watkinson G. Treatment of ulcerative colitis with topical hydrocortisone hemisuccinate sodium; a controlled trial employing restricted sequential analysis. BMJ 1958 Nov; 14(5103): 1077–82
Marshall JK, Irvine EJ. Rectal aminosalicylate therapy for distal ulcerative colitis: a meta-analysis. Aliment Pharmacol Ther 1995 Jun; 9(3): 293–300
Campieri M, Lanfranchi GA, Bazzocchi G, et al. Treatment of ulcerative colitis with high-dose 5-aminosalicylic acid enemas. Lancet 1981 Aug; II(8241): 270–1
Danish 5-ASA Group. Topical 5-aminosalicylic acid versus prednisolone in ulcerative proctosigmoiditis: a randomized, double-blind multicenter trial. Dig Dis Sci 1987 Jun; 32(6): 598–602
Farup PG, Hovde O, Halvorsen FA, et al. Mesalazine suppositories versus hydrocortisone foam in patients with distal ulcerative colitis: a comparison of the efficacy and practicality of two topical treatment regimens. Scand J Gastroenterol 1995 Feb; 30(2): 164–70
Lee FI, Jewell DP, Mani V, et al. A randomised trial comparing mesalazine and prednisolone foam enemas in patients with acute distal ulcerative colitis. Gut 1996 Feb; 38(2): 229–33
Marshall JK, Irvine EJ. Rectal corticosteroids versus alternative treatments in ulcerative colitis: a meta-analysis. Gut 1997 Jun; 40(6): 775–81
Hanauer SB. Dose-ranging study of mesalamine (PENTASA) enemas in the treatment of acute ulcerative proctosigmoiditis: results of a multicentered placebo-controlled trial. The US PENTASA Enema Study Group. Inflamm Bowel Dis 1998 May; 4(2): 79–83
van Bodegraven AA, Boer RO, Lourens J, et al. Distribution of mesalazine enemas in active and quiescent ulcerative colitis. Aliment Pharmacol Ther 1996 Jun; 10(3): 327–32
Brown J, Haines S, Wilding IR. Colonic spread of three rectally administered mesalazine (Pentasa) dosage forms in healthy volunteers as assessed by gamma scintigraphy. Aliment Pharmacol Ther 1997 Aug; 11(4): 685–91
Campieri M, Gionchetti P, Belluzzi A, et al. 5-Aminosalicylic acid as enemas or suppositories in distal ulcerative colitis? J Clin Gastroenterol 1988 Aug; 10(4): 406–9
Malchow H, Gertz B. A new mesalazine foam enema (Claversal Foam) compared with a standard liquid enema in patients with active distal ulcerative colitis. Aliment Pharmacol Ther 2002 Mar; 16(3): 415–23
Campieri M, Lanfranchi GA, Boschi S, et al. Topical administration of 5-aminosalicylic acid enemas in patients with ulcerative colitis: studies on rectal absorption and excretion. Gut 1985 Apr; 26(4): 400–5
Cann PA, Holdsworth CD. Systemic absorption from hydrocortisone foam enema in ulcerative colitis. Lancet 1987 Apr; I(8538): 922–3
Fraser AG, Orchard TR, Jewell DP. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut 2002 Apr; 50(4): 485–9
Rosenberg JL, Wall AJ, Levin B, et al. A controlled trial of azathioprine in the management of chronic ulcerative colitis. Gastroenterology 1975 Jul; 69(1): 96–9
Kirk AP, Lennard-Jones JE. Controlled trial of azathioprine in chronic ulcerative colitis. BMJ (Clin Res Ed) 1982 May; 284(6325): 1291–2
Hawthorne AB, Logan RF, Hawkey CJ, et al. Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. BMJ 1992 Jul; 305(6844): 20–2
Nielsen OH, Vainer B, Rask-Madsen J. Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine. Aliment Pharmacol Ther 2001 Nov; 15(11): 1699–708
Lennard L. The clinical pharmacology of 6-mercaptopurine. Eur J Clin Pharmacol 1992; 43(4): 329–39
Pearson DC, May GR, Fick GH, et al. Azathioprine and 6-mercaptopurine in Crohn disease: a meta-analysis. Ann Intern Med 1995 Jul; 123(2): 132–42
Sandborn WJ, Tremaine WJ, Wolf DC, et al. Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn’s disease: North American Azathioprine Study Group. Gastroenterology 1999 Sep; 117(3): 527–35
Weinshilboum R. Thiopurine pharmacogenetics: clinical and molecular studies of thiopurine methyltransferase. Drug Metab Dispos 2001 Apr; 29(4 Pt 2): 601–5
Colombel JF, Ferrari N, Debuysere H, et al. Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn’s disease and severe myelosuppression during azathioprine therapy. Gastroenterology 2000 Jun; 118(6): 1025–30
Lennard L. TPMT in the treatment of Crohn’s disease with azathioprine. Gut 2002 Aug; 51(2): 143–6
Matsuda S, Koyasu S. Mechanisms of action of cyclosporine. Immunopharmacology 2000 May; 47(2–3): 119–25
Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 1994 Jun; 330(26): 1841–5
D’Haens G, Lemmens L, Geboes K, et al. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology 2001 May; 120(6): 1323–9
Van Assche G, D’Haens G, Noman M, et al. Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Gastroenterology 2003 Oct; 125(4): 1025–31
Sandborn WJ. Cyclosporine in ulcerative colitis: state of the art. Acta Gastroenterol Belg 2001 Apr; 64(2): 201–4
Gummert JF, Ikonen T, Morris RE. Newer immunosuppressive drugs: a review. J Am Soc Nephrol 1999 Jun; 10(6): 1366–80
Fellermann K, Tanko Z, Herrlinger KR, et al. Response of refractory colitis to intravenous or oral tacrolimus (FK506). Inflamm Bowel Dis 2002 Sep; 8(5): 317–24
Baumgart DC, Wiedenmann B, Dignass AU. Rescue therapy with tacrolimus is effective in patients with severe and refractory inflammatory bowel disease. Aliment Pharmacol Ther 2003 May; 17(10): 1273–81
Bousvaros A, Kirschner BS, Werlin SL, et al. Oral tacrolimus treatment of severe colitis in children. J Pediatr 2000 Dec; 137(6): 794–9
Alfadhli AA, McDonald JW, Feagan BG. Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database Syst Rev 2003; (1): CD003459
Kremer JM. The mechanism of action of methotrexate in rheumatoid arthritis: the search continues. J Rheumatol 1994 Jan; 21(1): 1–5
Oren R, Arber N, Odes S, et al. Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial. Gastroenterology 1996 May; 110(5): 1416–21
Mate-Jimenez J, Hermida C, Cantero-Perona J, et al. 6-mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid-dependent inflammatory bowel disease. Eur J Gastroenterol Hepatol 2000 Nov; 12(11): 1227–33
Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999 May; 340(18): 1398–405
Arnott ID, McDonald D, Williams A, et al. Clinical use of Infliximab in Crohn’s disease: the Edinburgh experience. Aliment Pharmacol Ther 2001 Oct; 15(10): 1639–46
Nikolaus S, Raedler A, Kuhbacker T, et al. Mechanisms in failure of infliximab for Crohn’s disease. Lancet 2000 Oct; 356(9240): 1475–9
Chey WY, Hussain A, Ryan C, et al. Infliximab for refractory ulcerative colitis. Am J Gastroenterol 2001 Aug; 96(8): 2373–81
Kohn A, Prantera C, Pera A, et al. Anti-tumour necrosis factor alpha (infliximab) in the treatment of severe ulcerative colitis: result of an open study on 13 patients. Dig Liver Dis 2002 Sep; 34(9): 626–30
Jarnerot G, Hertervig E, Friis-Liby I, et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 2005 Jun; 128(7): 1805–11
Sands BE, Tremaine WJ, Sandborn WJ, et al. Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: a pilot study. Inflamm Bowel Dis 2001 May; 7(2): 83–8
Probert CS, Hearing SD, Schreiber S, et al. Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial. Gut 2003 Jul; 52(7): 998–1002
Ochsenkuhn T, Sackmann M, Goke B. Infliximab for acute, not steroid-refractory ulcerative colitis: a randomized pilot study. Eur J Gastroenterol Hepatol 2004 Nov; 16(11): 1167–71
Creed TJ, Norman MR, Probert CS, et al. Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis. Aliment Pharmacol Ther 2003 Jul; 18(1): 65–75
Van Assche G, Dalle I, Noman M, et al. A pilot study on the use of the humanized anti-interleukin-2 receptor antibody daclizumab in active ulcerative colitis. Am J Gastroenterol 2003 Feb; 98(2): 369–76
Gordon FH, Hamilton MI, Donoghue S, et al. A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to alpha-4 integrin. Aliment Pharmacol Ther 2002 Apr; 16(4): 699–705
Ljung T, Karlen P, Schmidt D, et al. Infliximab in inflammatory bowel disease: clinical outcome in a population based cohort from Stockholm County. Gut 2004 Jun; 53(6): 849–53
Kane SV, Cohen RD, Aikens JE, et al. Prevalence of nonadherence with maintenance mesalamine in quiescent ulcerative colitis. Am J Gastroenterol 2001 Oct; 96(10): 2929–33
Riley SA, Mani V, Goodman MJ, et al. Why do patients with ulcerative colitis relapse? Gut 1990 Feb; 31(2): 179–83
Kane S, Huo D, Aikens J, et al. Medication nonadherence and the outcomes of patients with quiescent ulcerative colitis. Am J Med 2003 Jan; 114(1): 39–43
Shale MJ, Riley SA. Studies of compliance with delayed-release mesalazine therapy in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2003 Jul; 18(2): 191–8
Moody GA, Eaden JA, Helyes Z, et al. Oral or rectal administration of drugs in IBD? Aliment Pharmacol Ther 1997 Oct; 11(5): 999–1000
Robinson A, Thompson DG, Wilkin D, et al. Guided self-management and patient-directed follow-up of ulcerative colitis: a randomised trial. Lancet 2001 Sep; 358(9286): 976–81
Green JR, Swan CH, Gibson JA, et al. Patient-led variable dosing with balsalazide as long-term therapy for maintenance in ulcerative colitis: a 3-year prospective observational study. Aliment Pharmacol Ther 2004 Feb; 19(4): 435–42
Acknowledgements
Dr Masson has no conflicts of interest. Dr Nylander has sat on the advisory board for Ferring Pharmaceuticals. Dr Mansfield has sat on advisory boards for Shire Pharmaceuticals and Ferring Pharmaceuticals within the last 5 years. Additionally, he has previously received sponsorship from Shire Pharmaceuticals and Procter & Gamble Pharmaceuticals, although he currently receives no funding from them. No pharmaceutical funding was used to assist in the preparation of this review.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Masson, S., Nylander, D. & Mansfield, J.C. How Important is Onset of Action in Ulcerative Colitis Therapy?. Drugs 65, 2069–2083 (2005). https://doi.org/10.2165/00003495-200565150-00001
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-200565150-00001