P318. Therapeutic depletion of myeloid lineage leucocytes in patients with ulcerative colitis: Demographic features of responders and non-responders to this non-pharmacological treatment option
T. Tanaka, S. Sugiyama, M. Akagi, H. Goishi, T. Kajihara, T. Miura, Akitsu Hospital, Gastroenterology, Hiroshima, Japan
Patients with active inflammatory bowel disease (IBD) have elevated myeloid lineage leucocytes, notably CD14(+)CD16(+) monocytes, which are sources of tumour necrosis factor-α (J Immunol 2002). Hence selective depletion of these leucocytes by granulocyte/monocyte adsorption (GMA) with an Adacolumn is expected to alleviate inflammation and promote remission or at least enhance drug efficacy. However, studies in ulcerative colitis (UC) reported contrasting efficacy, from an 85% (Suzuki, et al. Gastroenterology 2005) to a statistically insignificant level (Sands, et al. Gastroenterology 2008). Patients' demographic variables in the aforementioned studies were different.
In 141 UC patients we looked for clinical and endoscopic features which could indentify a patient as a responder or as a non-responder to GMA. Seventy-three patients were steroid naive, and 68 were steroid dependent. Patients received up to an 11 GMA sessions over 10 weeks. At entry and week 12, patients were clinically and endoscopically evaluated, allowing each patient to serve as her or his own control. Clinical activity index (CAI) ≤4 at week 12 was defined as response to GMA. Biopsies from colonoscopically detectable inflamed mucosa were processed to see the impact of GMA on leucocytes within the mucosa.
At entry the average CAI was 12.8, range 10–17. Ninety-two of the 141 patients (65.2%) responded to GMA, 52 of 73 steroid naïve patients (71.2%) and 40 of 68 steroid dependent patients (58.8%). On average remission was sustained for 8.6 months in steroid naïve patients and for 10.4 months in steroid dependent cohort. Upon relapse, the majority of patients responded well to a second course of GMA. Over 1200 biopsies were processed. Infiltrating leucocytes were overwhelmingly neutrophils and monocytes/macrophages. There was a marked reduction of infiltrating leucocytes in responders. Patients who had extensive deep UC lesions together with loss of the mucosal tissue at the lesion sites were identified as non-responders. Patients with the first UC episode were identified as the best responders (100%) followed by steroid naive patients. Additionally, a short duration of active UC marked a patient as a likely responder.
Depleting elevated myeloid lineage leucocytes was associated with efficacy in UC patients, most notably first episode and steroid naïve cases who attained a favourable future clinical course. GMA should be applied immediately after a relapse. Additionally, GMA was very much favoured by the patients for its safety profile and for being a non-drug therapeutic intervention. Patients with extensive deep ulcers, with long duration of UC and exposure to multiple pharmacologicals are unlikely to benefit from GMA.