Selective granulocyte and monocyte apheresis as a non-pharmacological option for patients with inflammatory bowel disease.
Ulcerative colitis and Crohn’s disease are the two most prevalent inflammatory bowel diseases. In both cases, the medically refractory and steroid-dependent type presents a therapeutic challenge. To help resolve this problem, a mainly Japanese team developed a new therapeutic option. There are two systems, both of which are able to selectively remove the main mediators of the disease, namely the activated pro-inflammatory cytokine-producing granulocytes and monocytes/macrophages, from the patient’s blood circulation (GMA = granulocyte monocyte apheresis). One of the two systems is the Adacolumn( (®) ) (Immunoresearch Laboratories, Takasaki, Japan) consisting of the ADA-monitor and a single-use column, which contains approximately 35,000 cellulose acetate beads. The exact mode of action is not yet sufficiently understood, but however, a modulation of the immune system takes place. As a result, less pro-inflammatory cytokines are released. Furthermore, the production of anti-inflammatory interleukin-1 receptor antagonist is increased, and the apoptosis of granulocytes boosted. The decreased LECAM-1-expression on leukocytes impedes the leukotaxis to the inflamed tissue, and CD10-negative immature granulocytes appear in the peripheral blood. Another effect to be mentioned is the removal of the peripheral dendritic cells and the leachate of regulatory T cells (T-regs). The second system is the Cellsorba( (®) ) FX Filter (Asahi Medical, Tokyo, Japan). The range of efficiency, the indication, and the procedure are very similar to the Adacolumn. Solely the additional removal of lymphocytes can possibly limit the implementation since lymphopenia can increase the risk of autoimmune disease. Both systems provide a low-risk therapy with few adverse reactions. ASFA recommendations for GMA in inflammatory bowel disease are 2B due to the fact that not enough randomized double-blind studies are available to proof the efficacy of this treatment.
Leukocytapheresis for the treatment of IBD
Fridrik Thor Sigurbjörnsson & Ingvar Bjarnason, Nature Clinical Practice Gastroenterology & Hepatology volume 5, pages509–516 (2008)
Leukocytapheresis is a controversial nonpharmacologic treatment for IBD, in which white blood cells–the effector cells of the inflammatory process–are mechanically removed from the circulation. Current controversy centers on the uncontrolled nature of the leukocytapheresis trials performed and their use of different outcome measures in patient groups that have very variable disease activity and severity. Nonetheless, the efficacy data obtained are generally quite consistent: an excellent response (remission >80%) has been achieved in corticosteroid-naïve patients with ulcerative colitis and an average remission rate of more than 50% has been achieved in patients who have steroid-dependent or refractory ulcerative colitis. Interestingly, the largest randomized, double-blind, sham-controlled study of granulocyte-monocyte apheresis in patients with moderate to severe ulcerative colitis failed to demonstrate efficacy for the induction of clinical remission or response. Regardless, leukocytapheresis seems to be remarkably safe. The precise positioning of leukocytapheresis in the treatment of ulcerative colitis is uncertain at present and will vary according to geography and patient preference for a safe, nonpharmacologic treatment. Further efficacy studies are required to assess what the optimal number and frequency of treatments is, in addition to the need for head-to-head comparisons with established drugs.
Enthusiasm for the use of leukocytapheresis in the treatment of patients with IBD (mainly ulcerative colitis) is fueled by the lack of serious adverse effects and tempered by the lack of conventional placebo-controlled data or head-to-head comparisons with potential competitors
Leukocytapheresis induces clinical remission in more than 80% of corticosteroid-naïve patients who have ulcerative colitis
Average remission rates are in excess of 50% in patients with moderate or severe ulcerative colitis and in patients with corticosteroid-dependent or corticosteroid-resistant ulcerative colitis
Data in Crohn’s disease are sparse and further studies are required
Leukocyte apheresis clearly has potential use in patients with ulcerative colitis, but to decide its precise positioning in treatment algorithms will require targeted studies
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