P341. Therapeutic depletion of myeloid lineage leucocytes in ulcerative colitis patients instead of pharmacological intervention: clinical and endoscopic features of responders and non-responders
T. Tanaka1, H. Goishi1, S. Sugiyama1, H. Yamada1, 1Akitsu Prefectural Hospital, Hiroshima, Japan
Most ulcerative colitis (UC) patients have elevated and activated myeloid leucocytes like CD14(+)CD16(+) monocytes as sources of TNF-alpha (J Immunol 2002; 168: 3536–42). Hence selective depletion of myeloid leucocytes by granulocyte/monocyte adsorption (GMA) with an Adacolumn is expected to promote remission of UC. However, hitherto studies reported contrasting efficacy, from an 85% (Cohen RD. Gastroenterology 2005) to statistically insignificant level (Sands, et al. Gastroenterology 2008). Patients' demographic variables in these studies were different, and need to be validated.
In 137 UC patients, we looked for demographic features, which could identify patients as responders or non-responders to GMA. Sixty-six patients were steroid dependent, and 71 were steroid naive. Each patient received 2 GMA sessions in the first week and then one session/week up to 11 sessions. 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 or less was defined as response to GMA. Biopsies from inflamed mucosa were processed to see the impact of GMA on leucocytes seen in the mucosa.
The average CAI was 12.8, range 10–17, and the overall, response rate was 63.8%. In responders, prednisolone dose was tapered by 50% every two weeks and most of these patients became steroid free. Over 1000 biopsies were processed. Infiltrating leucocytes were overwhelmingly neutrophils and macrophages. There was a marked reduction of infiltrating leucocytes post GMA. Colonoscopy revealed extensive deep UC lesions with virtually no mucosal tissue left at lesion sites in most non-responders. Patients with the first UC episode were identified as the best responders (100%) followed by steroid naive patients. Additionally, GMA immediately after a relapse marked a patient as a likely responder and vice versa.
GMA is very much favoured by patients for its safety profile and being a non-drug intervention. In this study, patients with extensive loss of the mucosal tissue, and those with exposure to multiple drugs notably corticosteroids over a long period of time were found to be unlikely responders to GMA. First episode and corticosteroid naïve patients together with those who received GMA immediately after a relapse responded well and were spared from pharmacological intervention. These understandings should save medical cost and reduce patients' morbidity time.