Objectives: Currently, there are no effective therapeutic agents for patients with primary sclerosing cholangitis (PSC). This study aimed to evaluate the safety and efficiency of immunosuppressive agents (IAs) for the treatment of PSC. Methods: The literatures were searched using the following keywords singly or in combination: PSC, treatments, IAs. The primary outcome was defined as the need for liver transplantation or mortality. Results: Two hundred sixty six patients from 7 eligible studies were analyzed. IAs had no remarkable effects on the rate of mortality or liver transplantation (relative risk, RR 1.02, 95% CI 0.58-1.62, p = 0.92). Subgroup analyses showed no significant effect of IAs co-administration therapy (IAs co-administered with ursodeoxycholic acid, IA co-administered with IA; RR 1.41, 95% CI 0.40-4.95, p = 0.60). IAs caused adverse events (AEs) such as diarrhea, abdominal pain, and pruritus (RR 1.81, 95% CI 1.07-3.07, p = 0.03). IAs therapy did not significantly improve markers of liver function except for aspartate transaminase (weighted mean difference -9.76, 95% CI -12.92 to -6.6, p < 0.001). Conclusion: IAs administrated as either monotherapy or combination therapy do not reduce the risk of mortality or liver transplantation. IAs monotherapy is associated with AEs.

Keywords:
Immunosuppressive agents, Primary sclerosing cholangitis, Meta-analysis
1.
Hirschfield GM, Karlsen TH, Lindor KD, Adams DH: Primary sclerosing cholangitis. Lancet 2013;382:1587-1599.
2.
Molodecky NA, Kareemi H, Parab R, et al: Incidence of primary sclerosing cholangitis: a systematic review and meta-analysis. Hepatology 2011;53:1590-1599.
3.
Lindor KD, Jorgensen RA, Anderson ML, et al: Ursodeoxycholic acid and methotrexate for primary sclerosing cholangitis: a pilot study. Am J Gastroenterol 1996;91:511-515.
4.
Knox TA, Kaplan MM: A double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis. Gastroenterology 1994;106:494-499.
5.
Triantos CK, Koukias NM, Nikolopoulou VN, Burroughs AK: Meta-analysis: ursodeoxycholic acid for primary sclerosing cholangitis. Aliment Pharmacol Ther 2011;34:901-910.
6.
Othman MO, Dunkelberg J, Roy PK: Urosdeoxycholic acid in primary sclerosing cholangitis: a meta-analysis and systematic review. Arab J Gastroenterol 2012;13:103-110.
7.
Hashimoto E, Lindor KD, Homburger HA, et al: Immunohistochemical characterization of hepatic lymphocytes in primary biliary cirrhosis in comparison with primary sclerosing cholangitis and autoimmune chronic active hepatitis. Mayo Clin Proc 1993;68:1049-1055.
8.
Eksteen B, Grant AJ, Miles A, et al: Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis. J Exp Med 2004;200:1511-1517.
9.
Fong DG, Lindor KD: Future directions in the medical treatment of primary sclerosing cholangitis: the need for combination drug therapy. Am J Gastroenterol 2000;95:1861-1862.
10.
Leiser A, Kadish U: Beneficial effect of colchicine in a case of sclerosing cholangitis. Am J Med Sci 1986;291:416-418.
11.
Kaplan MM, Arora S, Pincus SH: Primary sclerosing cholangitis and low-dose oral pulse methotrexate therapy. Clinical and histologic response. Ann Intern Med 1987;106:231-235.
12.
Lindor KD, Wiesner RH, Colwell LJ, Steiner B, Beaver S, LaRusso NF: The combination of prednisone and colchicine in patients with primary sclerosing cholangitis. Am J Gastroenterol 1991;86:57-61.
13.
LaRusso NF, Wiesner RH, Ludwig J, MacCarty RL, Beaver SJ, Zinsmeister AR: Prospective trial of penicillamine in primary sclerosing cholangitis. Gastroenterology 1988;95:1036-1042.
14.
Olsson R, Broomé U, Danielsson A, et al: Colchicine treatment of primary sclerosing cholangitis. Gastroenterology 1995;108:1199-1203.
15.
Sterling RK, Salvatori JJ, Luketic VA, et al: A prospective, randomized-controlled pilot study of ursodeoxycholic acid combined with mycophenolate mofetil in the treatment of primary sclerosing cholangitis. Aliment Pharmacol Ther 2004;20:943-949.
16.
Hommes DW, Erkelens W, Ponsioen C, et al: A double-blind, placebo-controlled, randomized study of infliximab in primary sclerosing cholangitis. J Clin Gastroenterol 2008;42:522-526.
17.
Higgins J, Green S: Cochrane Handbook for Systematic Reviews of Interventions. New York, Cochrane Collaboration, John Wiley and Sons, 2008.
18.
Taggart DP, D'Amico R, Altman DG: Effect of arterial revascularisation on survival: a systematic review of studies comparing bilateral and single internal mammary arteries. Lancet 2001;358:870-875.
19.
Wells G, Shea B, O'Connell D, et al: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Hospital Research Institute Web site. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (accessed March 15, 2012).
20.
Phillips B Ball C, Sackett D, et al: Levels of evidence and grades of recommendation. Oxford Centre for Evidence-based Medicine Web site. http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/.
21.
Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-634.
22.
Begg CB, Mazumdar M: Operating characteristics of a rank correlation test for publication bias. Biometrics 1994; 50:1088-1101.
23.
Bambha K, Kim WR, Talwalkar J, et al: Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology 2003;125:1364-1369.
24.
Lindkvist B, Benito de Valle M, Gullberg B, Bjornsson E: Incidence and prevalence of primary sclerosing cholangitis in a defined adult population in Sweden. Hepatology 2010;52:571-577.
25.
Tischendorf JJ, Hecker H, Kruger M, Manns MP, Meier PN: Characterization, outcome, and prognosis in 273 patients with primary sclerosing cholangitis: a single center study. Am J Gastroenterol 2007;102:107-114.
26.
Gordon FD: Primary sclerosing cholangitis. Surg Clin North Am 2008;88:1385-1407.
27.
Loftus EV Jr, Harewood GC, Loftus CG, et al: PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis. Gut 2005;54:91-96.
28.
Saich R, Chapman R: Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease. World J Gastroenterol 2008;1:331-337.
29.
Talwalkar JA, Lindor KD: Primary sclerosing cholangitis. Inflamm Bowel Dis 2005;11:62-72.
30.
Lindor KD, Kowdley KV, Harrison ME: ACG clinical guideline: primary sclerosing cholangitis. Am J Gastroenterol 2015;110:646-659; quiz 660.
31.
Boberg KM, Egeland T, Schrumpf E: Long-term effect of corticosteroid treatment in primary sclerosing cholangitis patients. Scand J Gastroenterol 2003;38:991-995.
32.
Allison MC, Burroughs AK, Noone P, Summerfield JA: Biliary lavage with corticosteroids in primary sclerosing cholangitis. A clinical, cholangiographic and bacteriological study. J Hepatol 1986;3:118-122.
33.
van Pesch V, Bartholome E, Bissay V, et al: Safety and efficacy of natalizumab in Belgian multiple sclerosis patients: subgroup analysis of the natalizumab observational program. Acta Neurol Belg 2014;114:167-178.
34.
Talwalkar JA, Gossard AA, Keach JC, Jorgensen RA, Petz JL, Lindor RN: Tacrolimus for the treatment of primary sclerosing cholangitis. Liver Int 2007;27:451-453.
35.
Talwalkar JA, Angulo P, Keach JC, Petz JL, Jorgensen RA, Lindor KD: Mycophenolate mofetil for the treatment of primary sclerosing cholangitis. Am J Gastroenterol 2005;100:308-312.
36.
Angulo P, Batts KP, Jorgensen RA, LaRusso NA, Lindor KD: Oral budesonide in the treatment of primary sclerosing cholangitis. Am J Gastroenterol 2000;95:2333-2337.
37.
Schramm C, Schirmacher P, Helmreich-Becker I, et al: Combined therapy with azathioprine, prednisolone, and ursodiol in patients with primary sclerosing cholangitis. A case series. Ann Intern Med 1999;13:943-946.
38.
Ponsioen CY, Vrouenraets SM, Prawirodirdjo W, et al: Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population. Gut 2002;51:562-566.
39.
Chen W, Gluud C: Glucocorticosteroids for primary sclerosing cholangitis. Cochrane Database Syst Rev 2004;3:CD004036.
40.
Hay JE, Lindor KD, Wiesner RH, Dickson ER, Krom RA, LaRusso NF: The metabolic bone disease of primary sclerosing cholangitis. Hepatology 1991;14:257-261.
© 2017 S. Karger AG, Basel
2017
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.