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

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.

Inflammatory Bowel Disease in Japan-Is It Similar to or Different from Westerns?-

“…Clinical remission was achieved in 30.0% of patients with previous immunosuppressant and biologic failure. These results are consistent with previous studies in Japan [25].…”

A multicenter retrospective study aiming to identify patients who respond well to adsorptive granulomonocytapheresis in moderately to severely active ulcerative colitis

“…Nevertheless, a large scale randomized controlled trial (RCT) conducted in North America failed to show efficacy in the induction of clinical remission or response in patients with moderate to severe UC 20 . The difference in GMA efficacy between this RCT and other studies 8 – 16 may be attributed to demographic/disease characteristics, medical histories, and past exposure to pharmacologic preparations. A subset of patients who might or might not respond to GMA has not been fully identified.…”

“…In Japan since April 2000 when GMA was approved as one treatment option for patients with active UC by the Japan Ministry of Health, it has been widely used for patients with UC, and to our knowledge, it is now available in the European Union countries. Multiple studies in Japan 8 – 12 and Europe 13 – 16 found that GMA was safe and therapeutically effective in patients with active UC. Additional evidence to support a therapeutic benefit from GMA should lead to a reduced need for pharmacologic preparations like corticosteroids, immunosuppressants, and biologicals which are associated with serious adverse side effects as additional morbidities 17 – 19 .…”

Granulomonocytapheresis as a cell‐dependent treatment option for patients with inflammatory bowel disease: Concepts and clinical features for better therapeutic outcomes

“…Hitherto, a large number of articles mostly from Japan, [51][52][53][54][55][56][57][58][59][60][61][62][63] Europe, [64][65][66][67][68][69][70][71][72][73][74][75][76][77] and the USA 78,79 have described the efficacy of GMA in patients with IBD. The clinical application of GMA with the Adacolumn began following a pioneering multicentre clinical trial by Shimoyama, et al 80 Since then, GMA has been widely applied in Japan and in the European Union (EU) countries to treat patients with IBD.…”

“…Further, the mean time to remission was 28.1 days, in group 1 and 16.3 days in group 2. In spite of these outcomes, our views are that the efficacy of GMA is time dependent, may take several weeks to be seen . As reviewed above, in patients with active IBD, large numbers of myeloid lineage leucocytes are found within the mucosal tissue, which may take several weeks to clear in spite of CAI showing clinical remission .…”