Safety and Efficacy of Granulocyte/Monocyte Apheresis in Steroid-Dependent Active Ulcerative Colitis with Insufficient Response or Intolerance to Immunosuppressants and/or Biologics [the ART Trial]: 12-week Interim Results

Axel Dignass, Ayesha Akbar, Ailsa Hart, Sreedhar Subramanian, Gilles Bommelaer, Daniel C Baumgart, Jean-Charles Grimaud, Guillaume Cadiot, Richard Makins, Syed Hoque, Guillaume Bouguen, Bruno Bonaz, Axel Dignass, Ayesha Akbar, Ailsa Hart, Sreedhar Subramanian, Gilles Bommelaer, Daniel C Baumgart, Jean-Charles Grimaud, Guillaume Cadiot, Richard Makins, Syed Hoque, Guillaume Bouguen, Bruno Bonaz

Abstract

Background and aims: Patients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup.

Methods: This single-arm, open-label, multicentre trial [ART] was conducted at 18 centres across the UK, France, and Germany. Eligible patients were 18-75 years old with moderate-to-severe, steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics. Patients received ≥ 5 weekly apheresis sessions with Adacolumn. The primary endpoint was clinical remission rate [clinical activity index ≤ 4] at Week 12.

Results: In all, 86 patients were enrolled. At Week 12, 33/84 [39.3%] of patients in the intention-to-treat population achieved clinical remission, with 47/84 [56.0%] achieving a clinical response [clinical activity index reduction of ≥ 3]. Clinical remission was achieved in 30.0% of patients with previous immunosuppressant and biologic failure; steroid-free clinical remission and response were observed in 22.6% and 35.7% of these patients, respectively. Quality of life [Short Health Scale] significantly improved at Week 12 [p < 0.0001]. The majority of adverse events were of mild/moderate intensity.

Conclusions: At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgroup.

Keywords: Ulcerative colitis; adacolumn; apheresis.

Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press.

Figures

Figure 1.
Figure 1.
Study design [a] and participant flow [b]. AE, adverse event; CAI, clinical activity index; EAI, endoscopic activity index; hsCRP, high sensitivity C-reactive protein; ITT, intention-to-treat; PP, per protocol; QoL, quality of life; Q1W, every week.
Figure 2.
Figure 2.
Time to [a] remission and [b] response for the ITT population. ITT, intention-to treat.
Figure 3.
Figure 3.
Time to [a] steroid-free remission and [b] steroid-free response for the ITT population. ITT, intention-to-treat.

References

    1. Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med 2011;365:1713–25.
    1. Dignass A, Eliakim R, Magro F, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 1: Definitions and diagnosis. J Crohns Colitis 2012;6:965–90.
    1. Dignass A, Lindsay JO, Sturm A, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 2: current management. J Crohns Colitis 2012;6:991–1030.
    1. Bär F, Sina C, Fellermann K. Thiopurines in inflammatory bowel disease revisited. World J Gastroenterol 2013;19 1699–706.
    1. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med 2013;369:699–710.
    1. Saniabadi AR, Tanaka T, Ohmori T, Sawada K, Yamamoto T, Hanai H. Treating inflammatory bowel disease by adsorptive leucocytapheresis: a desire to treat without drugs. World J Gastroenterol 2014;20:9699–715.
    1. Vecchi M, Vernia P, Riegler G, D’Incà R, Annese V, Bagnoli S. Therapeutic landscape for ulcerative colitis: where is the Adacolumn[®] system and where should it be? Clin Exp Gastroenterol 2013;6:1–7.
    1. Matsumoto T, Andoh A, Okawa K, et al. Multivariate analysis for factors predicting rapid response of leukocytapheresis in patients with steroid-resistant ulcerative colitis: a multicenter prospective open-label study. Ther Apher Dial 2008;12:484–90.
    1. Hanai H, Takeda Y, Eberhardson M, et al. The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review. Clin Exp Immunol 2011;163:50–8.
    1. Kashiwagi N, Hirata I, Kasukawa R. A role for granulocyte and monocyte apheresis in the treatment of rheumatoid arthritis. Ther Apher Dial 1998;2:134–41.
    1. Saniabadi AR, Hanai H, Takeuchi K, et al. Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial 2003;7:48–59.
    1. Habermalz B, Sauerland S. Clinical effectiveness of selective granulocyte, monocyte adsorptive apheresis with the Adacolumn device in ulcerative colitis. Dig Dis Sci 2010;55:1421–8.
    1. Thanaraj S, Hamlin PJ, Ford AC. Systematic review: granulocyte/monocyte adsorptive apheresis for ulcerative colitis. Aliment Pharmacol Ther 2010;32:1297–306.
    1. Zhu M, Xu X, Nie F, Tong J, Xiao S, Ran Z. The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis. Int J Colorectal Dis 2011;26:999–1007.
    1. Cabriada JL, Domènech E, Ibargoyen N, et al. Leukocytapheresis for steroid-dependent ulcerative colitis in clinical practice: results of a nationwide Spanish registry. J Gastroenterol 2012;47:359–65.
    1. Kruis W, Dignass A, Steinhagen-Thiessen E, et al. Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis. World J Gastroenterol 2005;11:7001–6.
    1. Rachmilewitz D. Coated mesalazine [5-aminosalicylic acid] versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. BMJ 1989;298:82–6.
    1. Yamamato T, Umegae S, Matsumoto K. Safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis therapy for ulcerative colitis. World J Gastroenterol 2006;12:520–5.
    1. Hjortswang H, Järnerot G, Curman B, et al. The Short Health Scale: a valid measure of subjective health in ulcerative colitis. Scand J Gastroenterol 2006;41:1196–203
    1. Lehmann FS, Burri E, Beglinger C. The role and utility of faecal markers in inflammatory bowel disease. Ther Adv Gastroenterol 2015;8:23–36.
    1. Dignass AU, Eriksson A, Kilander A, Pukitis A, Rhodes JM, Vavricka S. Clinical trial: five or ten cycles of granulocyte-monocyte apheresis show equivalent efficacy and safety in ulcerative colitis. Aliment Pharmacol Ther 2010;31:1286–95.
    1. Sands BE, Sandborn WJ, Feagan B, et al. A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis. Gastroenterology 2008;135:400–9.
    1. Kruis W, Nguyen P, Morgenstern J. Granulocyte/Monocyte Adsorptive Apheresis in Moderate to Severe Ulcerative Colitis Effective or Not? Digestion 2015;92:39–44.
    1. Rahier JF, Ben-Horin S, Chowers Y, et al. European Evidence-based Consensus on the prevention, diagnosis, and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis 2009;3:47–91.
    1. Siegel CA, Marden SM, Persing SM, Larson RJ, Sands BE. Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn’s disease: a meta-analysis. Clin Gastroenterol Hepatol 2009;7:874–81.
    1. Kane SV, Brixner D, Rubin DT, Sewitch MJ. The challenge of compliance and persistence: focus on ulcerative colitis. J Manag Care Pharm 2008;14[1 Suppl A]:s2–12; quiz s13–5.
    1. Irvine EJ. Patients’ fears and unmet needs in inflammatory bowel disease. Aliment Pharmacol Ther 2004;20:54–9.
    1. Satsangi J, Silverberg MS, Vermeire S, Colombel J. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006;55:749–53.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe