Risk Factors and Treatment of Relapses in Autoimmune Pancreatitis: Rituximab is Safe and Effective

Overview

Journal United European Gastroenterol J

Publisher Wiley

Specialty Gastroenterology

Date 2019 Oct 31

PMID 31662864

Citations 19

Authors

Heithem Soliman

Marie-Pierre Vullierme

Frederique Maire

Olivia Hentic

Philippe Ruszniewski

Philippe Levy

Vinciane Rebours

Affiliations

Soon will be listed here.

Abstract

Background And Aims: Steroid therapy is the first-line treatment for autoimmune pancreatitis but relapses are frequent. The aims were to assess the efficacy and the safety of immunomodulator treatments for relapsing autoimmune pancreatitis and rituximab in particular and to identify relapsing risk factors.

Methods: Patients followed for autoimmune pancreatitis from 2000 to 2016 were included. Data were retrospectively analysed regarding autoimmune pancreatitis treatment.

Results: In total, 162 patients with autoimmune pancreatitis type 1 ( = 92) and type 2 ( = 70) were included (median follow-up: 3 years (0.5-14). Relapse occurred in 46.5% of patients with autoimmune pancreatitis type 1 (vs 19.3% in autoimmune pancreatitis 2; < 0.001). Risk factors of relapse were cholangitis, initial use of steroids, other organ involvement and chronic pancreatitis in autoimmune pancreatitis type 1 and initial use of steroids, tobacco consumption and chronic pancreatitis for autoimmune pancreatitis type 2. Overall, 21 patients were treated with immunomodulators (azathioprine, = 19, or methotrexate, = 2) for relapses. The efficiency rate was 67%. A total of 17 patients were treated with rituximab, with two perfusions at 15 days apart. The efficacy was 94% (16/17), significantly better than immunomodulator drugs ( = 0.03), with a median follow-up of 20 months (11-44). Only two patients needed two supplementary perfusions.

Conclusion: In relapsing autoimmune pancreatitis, rituximab is more efficient than immunomodulator drugs and shows better tolerance.

Citing Articles

Recent Evidence of the Role of CD4 T Cell Subsets in IgG4-related Disease.

Kamekura R, Sakamoto H, Yajima R, Yamamoto K, Okuni T, Yamamoto M JMA J. 2025; 8(1):40-47.

PMID: 39926068 PMC: 11799721. DOI: 10.31662/jmaj.2024-0096.

A Rare Case of Coronary Involvement in IgG4-Related Disease.

Nishijo D, Nakanishi K, Kono M, Shimada S, Komuro I JACC Case Rep. 2024; 29(6):102254.

PMID: 38549856 PMC: 10966370. DOI: 10.1016/j.jaccas.2024.102254.

Autoimmune pancreatitis: Cornerstones and future perspectives.

Gallo C, Dispinzieri G, Zucchini N, Invernizzi P, Massironi S World J Gastroenterol. 2024; 30(8):817-832.

PMID: 38516247 PMC: 10950636. DOI: 10.3748/wjg.v30.i8.817.

Treatment approaches in autoimmune pancreatitis (Review).

Padureanu V, Dragoescu A, Padureanu R, Rosu M, Radulescu D, Dop D Biomed Rep. 2024; 20(2):26.

PMID: 38259589 PMC: 10801350. DOI: 10.3892/br.2023.1714.

Challenges for clinicians treating autoimmune pancreatitis: Current perspectives.

Kim S, Lee Y, Chon H World J Clin Cases. 2023; 11(1):30-46.

PMID: 36687190 PMC: 9846983. DOI: 10.12998/wjcc.v11.i1.30.

References

Khosroshahi A, Carruthers M, Deshpande V, Unizony S, Bloch D, Stone J . Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients. Medicine (Baltimore). 2012; 91(1):57-66. DOI: 10.1097/MD.0b013e3182431ef6. View

Tacelli M, Celsa C, Magro B, Barresi L, Guastella S, Capurso G . Risk Factors for Rate of Relapse and Effects of Steroid Maintenance Therapy in Patients With Autoimmune Pancreatitis: Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2018; 17(6):1061-1072.e8. DOI: 10.1016/j.cgh.2018.09.051. View

Hart P, Kamisawa T, Brugge W, Chung J, Culver E, Czako L . Long-term outcomes of autoimmune pancreatitis: a multicentre, international analysis. Gut. 2012; 62(12):1771-6. PMC: 3862979. DOI: 10.1136/gutjnl-2012-303617. View

Mattoo H, Mahajan V, Maehara T, Deshpande V, Della-Torre E, Wallace Z . Clonal expansion of CD4(+) cytotoxic T lymphocytes in patients with IgG4-related disease. J Allergy Clin Immunol. 2016; 138(3):825-838. PMC: 5014627. DOI: 10.1016/j.jaci.2015.12.1330. View

de Pretis N, Amodio A, Bernardoni L, Campagnola P, Capuano F, Chari S . Azathioprine Maintenance Therapy to Prevent Relapses in Autoimmune Pancreatitis. Clin Transl Gastroenterol. 2017; 8(4):e90. PMC: 5543465. DOI: 10.1038/ctg.2017.17. View

Maire F, Le Baleur Y, Rebours V, Vullierme M, Couvelard A, Voitot H . Outcome of patients with type 1 or 2 autoimmune pancreatitis. Am J Gastroenterol. 2010; 106(1):151-6. DOI: 10.1038/ajg.2010.314. View

Beaugerie L, Brousse N, Bouvier A, Colombel J, Lemann M, Cosnes J . Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet. 2009; 374(9701):1617-25. DOI: 10.1016/S0140-6736(09)61302-7. View

Masamune A, Nishimori I, Kikuta K, Tsuji I, Mizuno N, Iiyama T . Randomised controlled trial of long-term maintenance corticosteroid therapy in patients with autoimmune pancreatitis. Gut. 2016; 66(3):487-494. DOI: 10.1136/gutjnl-2016-312049. View

Mattoo H, Mahajan V, Della-Torre E, Sekigami Y, Carruthers M, Wallace Z . De novo oligoclonal expansions of circulating plasmablasts in active and relapsing IgG4-related disease. J Allergy Clin Immunol. 2014; 134(3):679-87. PMC: 4149918. DOI: 10.1016/j.jaci.2014.03.034. View

10.

Zamboni G, Luttges J, Capelli P, Frulloni L, Cavallini G, Pederzoli P . Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens. Virchows Arch. 2004; 445(6):552-63. DOI: 10.1007/s00428-004-1140-z. View

11.

Ghazale A, Chari S, Zhang L, Smyrk T, Takahashi N, Levy M . Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008; 134(3):706-15. DOI: 10.1053/j.gastro.2007.12.009. View

12.

van Vollenhoven R, Emery P, Bingham 3rd C, Keystone E, Fleischmann R, Furst D . Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on adverse events of interest in RA patients. Ann Rheum Dis. 2012; 72(9):1496-502. PMC: 3756452. DOI: 10.1136/annrheumdis-2012-201956. View

13.

Shimosegawa T, Chari S, Frulloni L, Kamisawa T, Kawa S, Mino-Kenudson M . International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas. 2011; 40(3):352-8. DOI: 10.1097/MPA.0b013e3182142fd2. View

14.

Saeki T, Kawano M, Mizushima I, Yamamoto M, Wada Y, Nakashima H . The clinical course of patients with IgG4-related kidney disease. Kidney Int. 2013; 84(4):826-33. DOI: 10.1038/ki.2013.191. View

15.

Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T . Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 2012; 22(1):21-30. DOI: 10.1007/s10165-011-0571-z. View

16.

Sandanayake N, Church N, Chapman M, Johnson G, Dhar D, Amin Z . Presentation and management of post-treatment relapse in autoimmune pancreatitis/immunoglobulin G4-associated cholangitis. Clin Gastroenterol Hepatol. 2009; 7(10):1089-96. DOI: 10.1016/j.cgh.2009.03.021. View

17.

Sah R, Chari S, Pannala R, Sugumar A, Clain J, Levy M . Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. Gastroenterology. 2010; 139(1):140-8. DOI: 10.1053/j.gastro.2010.03.054. View

18.

Kamisawa T, Notohara K, Shimosegawa T . Two clinicopathologic subtypes of autoimmune pancreatitis: LPSP and IDCP. Gastroenterology. 2010; 139(1):22-5. DOI: 10.1053/j.gastro.2010.05.019. View

19.

Ebbo M, Grados A, Samson M, Groh M, Loundou A, Rigolet A . Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients. PLoS One. 2017; 12(9):e0183844. PMC: 5600376. DOI: 10.1371/journal.pone.0183844. View

20.

Kamisawa T, Shimosegawa T, Okazaki K, Nishino T, Watanabe H, Kanno A . Standard steroid treatment for autoimmune pancreatitis. Gut. 2009; 58(11):1504-7. DOI: 10.1136/gut.2008.172908. View