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Efficacy of apheresis as maintenance therapy for patients with ulcerative colitis in an open-label prospective multicenter randomised controlled trial

Makoto NaganumaYoko YokoyamaSatoshi MotoyaKenji WatanabeKoji SawadaFumito HiraiTakayuki YamamotoHiroyuki HanaiTeppei OmoriTakanori Kanai & Toshifumi Hibi, Journal of Gastroenterology volume 55, pages390–400 (2020)

Apheresis was well tolerated as maintenance therapy for UC although the cumulative clinical remission rate at 12 months was comparable between the apheresis and control groups.

Efficacy of apheresis as maintenance therapy for patients with ulcerative colitis in an open-label prospective multicenter https://link.springer.com/article/10.1007/s00535-019-01651-0#group-1

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Efficacy of granulocyte and monocyte apheresis for antibiotic-refractory pouchitis after proctocolectomy for ulcerative colitis: an open-label, prospective, multicentre study

Takayuki Yamamoto 1Toshiaki Tanaka 2Tadashi Yokoyama 3Takahiro Shimoyama 1Hiroki Ikeuchi 4Motoi Uchino 4Toshiaki Watanabe 5 , Therap Adv Gastroenterol. 2017 Feb;10(2):199-206.

GMA has a good safety profile, but its efficacy appears to be limited in the management of chronic refractory pouchitis. However, a large controlled study should be conducted to evaluate the efficacy of GMA therapy in patients with pouchitis at an earlier clinical stage, before the disease has become refractory to conventional medical therapy.

https://pubmed.ncbi.nlm.nih.gov/28203278/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298477/pdf/10.1177_1756283X16679348.pdf

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Leukocytapheresis in pediatric patients with ulcerative colitis

Takeshi Tomomasa 1Hitoshi TajiriSeiichi KagimotoToshiaki ShimizuAtsushi YodenKosuke UshijimaKeiichi UchidaHiroaki KanekoDaiki AbukawaMutsuko KonnoShun-ichi MaisawaTakao KohsakaAkio KobayashiJapanese Study Group for Pediatric Ulcerative Colitis. J Pediatr Gastroenterol Nutr. 2011 Jul;53(1):34-9. doi: 10.1097/MPG.0b013e31821058bc.

Objective: Leukocytapheresis (LCAP) is a nonpharmacologic therapy that has recently been used to treat ulcerative colitis (UC). This multicenter open-label study prospectively assessed the efficacy and safety of LCAP in pediatric patients with UC. Patients and methods: Twenty-three patients ages 8 to 16 years with moderate (n = 19) to severe (n = 4) steroid-resistant UC were enrolled. One of 2 LCAP columns with different volumes (model EX and the half-volume model EI) was selected, according to body weight. LCAP was performed once per week for 5 consecutive weeks. Clinical and laboratory data were collected at predetermined time points. The primary endpoint was decreased stool frequency/hematochezia score, and secondary endpoints were clinical, laboratory, and endoscopic improvements. Results: The stool frequency/hematochezia score decreased significantly from 4.5 ± 1.2 before treatment to 1.6 ± 1.9 after the fifth treatment. Clinical parameters, including stool frequency, presence of visible blood, abdominal pain, and body temperature, were significantly improved. Fecal calprotectin decreased significantly. Endoscopic findings evaluated using Matts score also improved (P < 0.01). The steroid dose decreased from 1.1 ± 0.4 mg/kg before treatment to 0.8 ± 0.5 mg/kg after treatment. There were no significant differences in changes between the EX and EI columns. The incidence of adverse effects was 61%, although none was serious. The most common adverse effects were decreased hematocrit and hemoglobin concentration. Conclusions: The present study showed that LCAP was well tolerated in children with UC, mostly moderate, and was as effective as in adults. The types of pediatric patients best suited to LCAP remain to be determined.

https://pubmed.ncbi.nlm.nih.gov/21694533/

Leukocytapheresis in Pediatric Patients With Ulcerative Coli… : Journal of Pediatric Gastroenterology and Nutrition (lww.com)

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An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn’s disease.

Atsushi Sakuraba 1Satoshi MotoyaKenji WatanabeMasakazu NishishitaKazunari KankeToshiyuki MatsuiYasuo SuzukiTadayuki OshimaReiko KunisakiTakayuki MatsumotoHiroyuki HanaiKen FukunagaNaoki YoshimuraToshimi ChibaShinsuke FunakoshiNobuo AoyamaAkira AndohHiroshi NakaseYohei MizutaRyoichi SuzukiTaiji AkamatsuMasahiro IizukaToshifumi AshidaToshifumi Hibi, Am J Gastroenterol. 2009 Dec;104(12):2990-5.

Background: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn’s disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD. Methods: In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level). Results: Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/μL to 6950/μL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern. Conclusions: In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.

https://pubmed.ncbi.nlm.nih.gov/26585569/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653849/

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Leukocytapheresis in Patients with Moderate-Severe Steroid-Dependant Ulcerative Colitis: Clinical Response without Endoscopic Response

Irene Modesto, Daniela Scimeca, Ambrogio Orlando, Mario Cottone, Inflamm Bowel Dis 12 (10), October 2006

We report the results of an open prospective study of LCAP in moderate to severe steroid-dependent UC. LCAP is an effective procedure in obtaining discontinuation of steroids in 36% of patients with UC for at least 3 months. Overall 4 of 11(36%) patients could discontinue steroids within 3 months. No relevant side effects were observed. The procedure was well tolerated. In our series, there was no endoscopic response. Most of the patients obtained a clinical temporary response, but many relapsed

https://pubmed.ncbi.nlm.nih.gov/17012976/

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Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis

Wolfgang Kruis, Axel Dignass, Elisabeth Steinhagen-Thiessen, Julia Morgenstern, Joachim Mössner,
Stephan Schreiber, Maurizio Vecchi, Alberto Malesci, Max Reinshagen, Robert Löfberg

World J Gastroenterol 2005;11(44):7001-7006

AIM: To study the efficacy, safety, and feasibility of a granulocyte adsorptive type apheresis system for the treatment of patients with chronically active ulcerative colitis despite standard therapy. METHODS: An open label multicenter study was carried out in 39 patients with active ulcerative colitis (CAI 6-8) despite continuous use of steroids (a minimum total dose of 400 mg prednisone within the last 4 wk). Patients received a total of five aphereses using a granulocyte adsorptive technique (Adacolumn®, Otsuka Pharmaceutical Europe, UK). Assessments at wk 6 and during follow-up until 4 mo comprised clinical (CAI) and endoscopic (EI) activity index, histology, quality of life (IBDQ), and laboratory tests. RESULTS: Thirty-five out of thirty-nine patients were qualified for intent-to-treat analysis. After the apheresis treatment at wk 6, 13/35 (37.1%) patients achieved clinical remission and 10/35 (28.6%) patients had endoscopic remission (CAI<4, EI<4). Quality of life (IBDQ) increased significantly (24 points, P <0.01) at wk 6. Apheresis could be performed in all but one patient. Aphereses were well tolerated, only one patient experienced anemia. CONCLUSION: In patients with steroid refractory ulcerative colitis, five aphereses with a granulocyte/ monocyte depleting filter show potential short-term efficacy. Tolerability and technical feasibility of the procedure are excellent.

https://www.wjgnet.com/1007-9327/full/v11/i44/7001.htm

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[Granulocyte and monocyte adsorption apheresis in Korean conventional treatment-refractory patients with active ulcerative colitis: a prospective open-label multicenter study]

[Article in Korean ]Hyo Jong Kim 1Joo Sung KimDong Soo HanSuk-Kyun YangKi Baik HahmWoo In LeeSeog-Woon KwonJai Hyun ChoiWon Ho KimKyu Yong ChoiIn Sung Song Korean J Gastroenterol  2005 Jan;45(1):34-44. PMID: 15665566

Background/aims: In chronic inflammatory conditions such as ulcerative colitis (UC), the migration of granulocytes and monocytes/macrophages from the circulation into the colonic mucosa is especially important in maintaining inflammation. The aim of this trial was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with moderate-to-severe UC refractory to conventional drug therapies. Methods: Twenty-seven patients with moderate (55.6%) to severe (44.4%) active UC refractory to conventional drug therapies who had no changes in their conventional therapy regimen in the past two weeks before the recruitment were enrolled in an open-label trial. Concomitant medications were allowed, and steroids were tapered down according to the clinical activity during the course. We used an adsorptive type extracorporeal column (Adacolumn; JIMRO, Takasaki, Japan), which selectively adsorb granulocytes and monocytes. Patients took five apheresis sessions, each with 60 minutes duration for 5 consecutive weeks. The primary efficacy variables were clinical disease activity, short inflammatory bowel disease questionnaire (SIBDQ), C-reactive protein (CRP), and endoscopic scores. These variables were scored at regular intervals, and analyzed at week 7 on an intention-to-treat (ITT) principles. Results: At 7 weeks, 70.4% of patients showed overall improvement. Clinical disease activity (p < 0.0001), endoscopic score (p < 0.001), and the quality of life as assessed by SIBDQ (p < 0.0001) were significantly improved after the therapy. In 56.3% of concomitant steroid users, tapering down or discontinuation of steroids was possible. Treatment was well tolerated, and no severe adverse events were observed. Conclusions: Adacolumn was very efficacious in patients with moderate-to-severe active UC refractory to conventional drug therapy, but further assessment is needed.

https://pubmed.ncbi.nlm.nih.gov/15665566/

Scientific corner

Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study

E Domènech 1J HinojosaM Esteve-ComasF GomollónJ M HerreraG BastidaA ObradorR RuizC SaroM A GassullSpanish Group for the Study of Crohn’s Disease and Ulcerative Colitis (GETECCU)

Aliment Pharmacol Ther. 2004 Dec;20(11-12):1347-52. doi: 10.1111/j.1365-2036.2004.02288.x.

Background: Uncontrolled studies suggest that granulocyteaphaeresis might be useful in the management of active ulcerative colitis. Aim: To assess the efficacy of granulocyteaphaeresis treatment in active steroid-dependent inflammatory bowel disease. Methods: We conducted a multicentre, prospective, open, pilot study in patients with steroid-dependent inflammatory bowel disease. All patients were started on 60 mg/day of prednisone; after 1 week, a five-session programme of granulocyteaphaeresis (once per week) was started. The steroid dose was tapered weekly if there was clinical improvement. Remission was defined as an inactive clinical activity index together with complete withdrawal of steroids at week 6. The patients were followed up for at least 6 months or until disease relapse. Results: Twenty-six patients (14 ulcerative colitis, 12 Crohn’s disease) were included. More than a half had been previously treated with immunomodulators. Remission was achieved in 62 and 70% of ulcerative colitis and Crohn’s disease, respectively. During a median follow-up of 12.6 months, six of eight ulcerative colitis patients maintained their clinical remission; however, only one Crohn’s disease patient remained in remission after the first 6 months of follow-up. Conclusions: Granulocyteaphaeresis is a safe treatment option in inflammatory bowel disease. A five-session programme of granulocyteaphaeresis seems to be efficient in the treatment of steroid-dependent ulcerative colitis, but not in Crohn’s disease.

https://pubmed.ncbi.nlm.nih.gov/15606397/

https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2036.2004.02288.x

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