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For and Adsorption (GMA) to treat patients with active IBD

What is Adacolumn® Adacolumn® is an adsorptive type leukocytapheresis column, that contains cellulose acetate beads bathed in physiologic saline. As passes through the Adacolumn®, and / that are known to promote inflammatory bowel disease are Adacolumn® selectively adsorbed to the beads.

What is treatment with Adacolumn® The Adasystem, consiting of Adacolumn®, Adamonitor and Adacircuit, is needed to perform the treatment. Adacolumn® was CE-marked in 1999. For treatment with the Adacolumn® blood access is made via a simple veno- puncture in one of the patient’s arms. The blood passes through the Adacolumn® where activated granulocytes and monocytes/mac- rophages are removed and the blood returns to the patient via a venopuncture in the opposite arm. The extracorporeal flow rate is 30 ml/min and the duration of one treatment session is 60 min. A small dose of is used as an anticoagu- lant. Adasystem

A GENTLE REVOLUTION IN IBD THERAPY How does Adacolumn® work The immunomodalatory effects of leukocyteapheresis Adacolumn® selectively adsorbes granulocytes, Functional effect on monocytes/macro- Venous leukocyte and reduced blood granulocyte activity fages with the help of Fcγ and complement receptors. Approximately 65% of granulocytes and 55% of monocytes from Selective adsorption of the blood that passes granulocytes Functional and through the column, disorder monocyte/ macrophages are adsorbed. However Tissue through damage the count of blood cells cellulose acetate will not go down below Leukocyte beads transmigration the healthy level as the entrapped activated cells are rapidly replaced by mobilisation of in- 1. inhibition of leukocyte -10 rolling through reduced active, CD negative LECAM- expression leukocytes. This means Extracorporeal 2. Down-regulation of that apheresis with Ada- Adacolumn perfusion production (TNF- u, IL-1v) column® has rather a

3. Avoidance of damages qualitative than quantita- on the tissue tive effect, i.e. activated leukocytes are replaced by inactive cells. Ad- ditionally, Adacolumn® leukocyte adsorption is associated with sustained down-modulation of pro-inflammatory like TNF-u, IL-1v, IL-6 and IL-8 released by blood leukocytes together with down- modulation of L-selectin and the receptor CXCR3 which mediate migration of leukocytes from blood into the inflammatory tissue.

Ref: Saniabadi A, Hanai H, Löfberg R et al. Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leucocytes. J of Clinical Apheresis 2005; 20: 171-184.

Adacolumn® is manufactured by: Japan Immunoresearch Laboratories Co. Ltd. (JIMRO) Adamonitor is Manufactured by: www.adacolumn.net Otsuka Electronics Co. Ltd. Authorized representative in Europe: Otsuka Pharmaceutical Europe Ltd.

A GENTLE REVOLUTION IN IBD THERAPY