Atsushi Sakuraba 1, Satoshi Motoya, Kenji Watanabe, Masakazu Nishishita, Kazunari Kanke, Toshiyuki Matsui, Yasuo Suzuki, Tadayuki Oshima, Reiko Kunisaki, Takayuki Matsumoto, Hiroyuki Hanai, Ken Fukunaga, Naoki Yoshimura, Toshimi Chiba, Shinsuke Funakoshi, Nobuo Aoyama, Akira Andoh, Hiroshi Nakase, Yohei Mizuta, Ryoichi Suzuki, Taiji Akamatsu, Masahiro Iizuka, Toshifumi Ashida, Toshifumi Hibi
Tag: intensive
Scientific corner
An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment
Objectives: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. Methods: This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. Results: Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54.0%) in weekly GMA and in 52 of 73 patients (71.2%) in intensive GMA (P=0.029). The mean time to remission was 28.1+/-16.9 days in the weekly GMA treatment group and 14.9+/-9.5 days in the intensive GMA group (P<0.0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. Conclusions: Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients’ morbidity time without increasing the incidence of side effects.
apheresis / Clinical remission / gma / Granulocyte / intensive / Monocyte / Multicenter / treament / ulcerative colitis /
Scientific corner
Leukocytapheresis in a girl with severe ulcerative colitis refractory to corticosteroids, infliximab, and cyclosporine A
Katalin Dittrich, Markus Richter, Wolfgang Rascher, Henrik Köhler Inflamm Bowel Dis 2008 Oct;14(10):1466-7. doi: 10.1002/ibd.20464.
Although medical therapy remains the first-line treatment for UC, colectomy may be required for patients with severe medically refractory disease. Leukocytapheresis (LCAP) has been reported as a new line of therapy in
patients with UC. Only 2 pediatric case series, not including patients on immunosuppressive therapy or biologicals, treated with granulocytapheresis have been reported. The patient reported by us is the youngest to the best of our knowledge in which this LCAP technique was used . She had severe colitis refractory to corticosteroids, infliximab and yclosporine A. We were able to avoid colectomy and the procedure was well tolerated.
Clinical remission / Corticosteroids / cyclosporine A / gma / Infliximab / intensive / Leukocytapheresis / pediatric / Safety / severe / steroid / ulcerative colitis /
Scientific corner
A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis
Recently, selective granulocytapheresis (Adacolumn) has appeared as a new treatment for patients with inflammatory bowel disease. This study sought to determine predictors of response to this new nonpharmacologic mode of therapy by retrospectively evaluating 28 patients who received granulocytapheresis after experiencing active ulcerative colitis (UC). Between April 2000 and March 2004, 28 consecutive patients received granulocytapheresis for active UC with the Adacolumn, which is filled with cellulose acetate beads as the column leukocytapheresis carriers; the carriers adsorb granulocytes, monocytes/macrophages, and a small fraction of lymphocytes (FcgammaR and complement receptors bearing leukocytes). Each patient could receive up to 10 Adacolumn sessions, at 2 sessions per week. In 2004, clinical response was retrospectively evaluated. Seven days after the last Adacolumn session, 20 of 28 patients had remission (colitis activity index [CAI] < or =4) including all 8 patients who had their first UC episode. The mean duration of UC in the 8 first episode cases was 3.4 months compared with 40.2 months for all 28 patients and 65.4 months for the 8 nonresponders. The response to Adacolumn was independent of basal CAI. The 8 nonresponders were given conventional medication (CM) or cyclosporine (CsA) if the former failed. Two responded to CM, 3 to CsA, and 3 underwent colectomy. First UC episode and short disease duration appear good predictors of response to granulocytapheresis. Selective granulocytapheresis might be an effective first-line treatment.
Scientific corner
Leukocytapheresis (LCAP) for Management
of Fulminant Ulcerative Colitis with
Toxic Megacolon
Dig Dis Sci 2005 Apr;50(4):767-73. doi: 10.1007/s10620-005-2571-3.
Leukocytapheresis (LCAP) is a method of therapeutic apheresis to remove patients’ peripheral leukocytes by extracorporeal circulation. Previous studies showed that LCAP for the treatment of ulcerative colitis (UC) was more effective and had fewer adverse effects compared to high-dose steroid therapy. However, there are no reports on the application of LCAP for UC patients with toxic megacolon (TM). This study reports the effectiveness and safety of LCAP in treating patients with severe or fulminant UC with TM. Six patients were enrolled in this study and LCAP sessions were performed three times per week for 2 weeks, followed by four further times in the next 4 weeks. After completion of therapy, four patients improved in TM and went into the remission stage of UC. The average Rachmilewitz clinical activity index of these four patients improved from 19.5 to 1. The remaining two patients had to undergo colectomy, however, the symptoms had been mitigated by LCAP and the operations were completed without any problems. These results suggest that LCAP is an additional effective and safe option for TM management in preventing colectomy or for bridging to a safer operation.
Scientific corner
Selective granulocyte and monocyte adsorptive apheresis as a first-line treatment for steroid naïve patients with active ulcerative colitis: a prospective uncontrolled study
Corticosteroid therapy of ulcerative colitis (UC) is associated with frequent adverse side effects and poor quality of life. Recently, adsorptive granulocyte and monocyte/macrophage apheresis has shown efficacy in patients with severe steroid refractory UC. The objective of this study was to investigate if, instead of corticosteroids, adsorptive leukocytapheresis has efficacy as the first-line therapy for steroid-naïve patients with active UC. Twenty patients, aged 15-49 years, with a mean clinical activity index (CAI) of 8.6 were recruited. Adsorptive leukocytapheresis was done with Adacolumn, which contains cellulose acetate beads as adsorptive carriers for granulocytes and monocytes (FcgammaR and complement receptors expressing leukocytes). Each patient received 6 to 10 leukocytapheresis sessions of 60-min duration, at 2 sessions/week. Efficacy was assessed 1 week after the last session. Post treatment, the mean CAI was 3.0 (P = 0001), and 17 of 20 patients (85%) were in remission. There were significant falls in C-reactive protein (P = 0.0003), total white cell counts (P = 0.003), neutrophils (P = 0.0029), and monocytes (P = 0.0038), an increase in lymphocytes (P = 0.001), and increases in the blood levels of soluble TNF-alpha receptors I (P = 0.0007) and II (P = 0.0045) in the column outflow (blood return to the patients). Further, at 8 months, 60% of patients had maintained their remission. No severe side effects were reported. In conclusion, adsorptive leukocytapheresis should reduce corticosteroid therapy in patients with moderate UC; cases with early-stage active disease may benefit most.
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A role for granulocyte and monocyte apheresis in the treatment of rheumatoid arthritis
Rheumatoid arthritis (RA) is an inflammatory condition, the etiology of which is not well understood. Recent reports indicate a major role of granulocytes in the pathogenesis of RA; arthritic joints are infiltrated with phagocytic leukocytes, granulocytes, and monocytes/macrophages, and it is believed that these cells, by releasing degradative proteinases, cytokines, and reactive oxygen species, contribute to joint destruction. Hence, the apheresis of granulocytes and monocytes may benefit patients with RA. Granulocyte and monocyte apheresis was carried out in 143 patients with RA using an apheresis column (G-1) packed with 220 g cellulose acetate beads, which selectively adsorb granulocytes and monocytes. Patients received 1 or 2 apheresis sessions, each of 1 h duration per week over a 4 week period at a flow rate of 30 ml/min. Apheresis significantly reduced swollen and tender joint counts and the duration of morning stiffness, and it increased grip strength, together with suppression of tumor necrosis factor-alpha and interleukin-1beta production by peripheral blood monocytes. It is concluded that this alternative treatment induces a kind of immunomodulation.
degranulation / gma / Granulocyte / immunology / immunomodulation / infiltration / intensive / MOA / Monocyte / rheumatoid arthritis /
Scientific corner
A role for granulocyte and monocyte apheresis in the treatment of rheumatoid arthritis
Rheumatoid arthritis (RA) is an inflammatory condition, the etiology of which is not well understood. Recent reports indicate a major role of granulocytes in the pathogenesis of RA; arthritic joints are infiltrated with phagocytic leukocytes, granulocytes, and monocytes/macrophages, and it is believed that these cells, by releasing degradative proteinases, cytokines, and reactive oxygen species, contribute to joint destruction. Hence, the apheresis of granulocytes and monocytes may benefit patients with RA. Granulocyte and monocyte apheresis was carried out in 143 patients with RA using an apheresis column (G-1) packed with 220 g cellulose acetate beads, which selectively adsorb granulocytes and monocytes. Patients received 1 or 2 apheresis sessions, each of 1 h duration per week over a 4 week period at a flow rate of 30 ml/min. Apheresis significantly reduced swollen and tender joint counts and the duration of morning stiffness, and it increased grip strength, together with suppression of tumor necrosis factor-alpha and interleukin-1beta production by peripheral blood monocytes. It is concluded that this alternative treatment induces a kind of immunomodulation.
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