P511 Efficacy and safety of granulocyte/monocyte adsorptive apheresis in steroid-dependent Active Ulcerative Colitis with insufficient response or intolerance to immunosuppressants and/or biological therapies (the ART trial): Results at 24 and 48 weeks
A. Dignass*1, A. Akbar2, B. Bonaz3
1Agaplesion Markus Hospital, Department of Medicine I, Frankfurt, Germany, 2St Mark's Hospital, Gastroenterology, London, United Kingdom, 3CHU de Grenoble, Clinique Universitaire d'Hépato-Gastroentérologie, Grenoble, France
Treatment options in steroid-dependent, chronic-active ulcerative colitis (UC) with insufficient response or intolerance to immunosuppressants and/or biologicals are limited. The ART trial intended to document efficacy and to describe difficult-to-treat UC subpopulations which could benefit from Granulocyte/ Monocyte adsorptive (GMA) apheresis (Adacolumn®).
This was an uncontrolled, open-label, multicenter trial conducted in the UK, France and Germany. 86 patients (18-75 years) with steroid-dependent active UC (Clinical Activity Index (CAI) ≥ 6; Endoscopic Activity Index (EAI) ≥ 4) and insufficient response or intolerance to immunosuppressants (IS) and/or TNF inhibitors were included. Patients received up to 8 GMA aphereses in a single induction series over up to 8 weeks. Primary endpoint was the remission rate (CAI ≤ 4) at Week 12; secondary efficacy endpoints were clinical response (reduction in CAI of ≥ 3), and steroid-free remission and response rates in the Intention-to-treat (ITT) population. Patients remained enrolled for the duration of the follow-up; concomitant medication changes were recorded. Endpoint analyses up to 48 Weeks used a conservative approach including additional analyses of sustained remission and response, defined as the respective events observed at Weeks 12, and 24, and 48.
As previously reported , among 84 patients in ITT, remission and response rates were 39.3% and 55.9% in Week 12. We now report remission rates of 34.5% in Week 24 and 33.3% in Week 48; response was seen in 46.4% and 39.3%, respectively. Out of 30 patients with prior failure of IS and biologicals, 33.3% were in remission in Week 24 and 20% at Week 48. Steroid-free remission at Week 24 was achieved by 19%, and 15.5% at Week 48. Sustained remission or response was seen in 29.8 % of patients at 48 Weeks. Concomitant IS medication was kept stable, steroid dose equivalents were reduced, and QoL improved further. 30 patients (41.7%) experienced at least 1 AE during follow-up; fifteen subjects experienced SAEs. None of the SAEs was related to the treatment. No new safety signals were seen.
We describe a cohort of steroid-dependent moderate to severe active UC patients with ineffectivity or intolerance to IS and/or biologicals treated with GMA apheresis induction therapy. Cinical benefit was seen in over 50% of patients at Week 12, in 46.4% at Week 24, and in 39.3% at Week 48. GMA apheresis may be a safe alternative treatment option in patients with UC failing or intolerant to immunosuppressants and TNF-inhibitors. Further randomized controlled clinical trials seem warranted to identify the place of GMA in the current treatment algorithms of UC.
 Dignass, et al., (2014), Efficacy and safety of GMA apheresis in steroid-dependent active UC with insufficient response or intolerance to immunosuppressants and/or biological therapies (the ART trial): Results at 12 weeks , P500, ECCO 2014 Copenhagen