Yusuke Okuyama,Akira Andoh,Masakazu Nishishita,Ken Fukunaga,Koji Kamikozuru,Yoko Yokoyama,Yoshitaka Ueno,Shinji Tanaka,Hiroyuki Kuge,Syusaku Yoshikawa,Atsushi Sugahara,Emi Anami,Yoshinori Munetomo,Chiyuki Watanabe,Yoshihide Fujiyama &Takayuki Matsumoto Scand. J. Gastro. 2013, 48 (4), 412-418. https://doi.org/10.3109/00365521.2012.763175
Tag: Leukocytapheresis
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Multicenter prospective study for clinical and endoscopic efficacies of leukocytapheresis therapy in patients with ulcerative colitis
Objective. This study aimed to assess the efficacy and tolerability of leukocytapheresis (LCAP) and to investigate predictive factors for mucosal healing and a sustained clinical response in steroid-free and steroid-refractory patients with ulcerative colitis (UC). Material and methods. Thirty-one steroid-free or steroid-refractory patients with active UC were enrolled. Five or ten consecutive sessions of LCAP were performed in each patient. The efficacy and tolerability was then evaluated at weeks 3 and 6. Endoscopic examination was performed at week 6 to evaluate the mucosal healing, and the sustained cumulative response rate was evaluated at 12 months. Results. At week 6, the mean Mayo clinical activity score had decreased significantly from 8.0 to 4.6 in the steroid-free patients and from 8.3 to 3.9 in the steroid-refractory patients. Rachmilewitz’s endoscopic index had also decreased significantly from 9.1 to 6.1 in the steroid-free patients and from 10.0 to 5.7 in the steroid-refractory patients. Forty-seven percent of the steroid-free patients and 33% of the steroid-refractory patients achieved mucosal healing. The peripheral platelet counts had decreased significantly at weeks 3 and 6 in the mucosal healing group, compared with the non-mucosal healing group. The patients with a more than 15% platelet reduction had a significantly higher cumulative response rate, compared with the patients without a platelet reduction (p = 0.015). Conclusions. LCAP is beneficial for the induction of mucosal healing in steroid-free and steroid-refractory patients with UC. The degree of platelet reduction during LCAP might be a predictive marker for mucosal healing and a sustained clinical response.
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Leukocytapheresis for steroid-dependent ulcerative colitis in clinical practice: results of a nationwide Spanish registry
J L Cabriada 1, E Domènech, N Ibargoyen, V Hernández, J Clofent, D Ginard, I Gutiérrez-Ibarluzea, J Hinojosa, J Gastroenterol. 2012 Apr;47(4):359-65.
Background: Several small, prospective, open studies suggest that leukocytapheresis might be efficient in patients with steroid-dependent ulcerative colitis (UC). Aim: To evaluate the short- and long-term effectiveness of leukocytapheresis for the management of steroid-dependent UC in clinical practice. Methods: A Web-based, nationwide database specifically designed to record the efficacy and safety data of leukocytapheresis therapy in UC was available from September 2007 in Spain. Clinical data were collected at treatment baseline, 1 month after the last apheresis session (initial efficacy), and 6 and 12 months thereafter (long-term efficacy). Remission was defined as a Mayo Clinic index ≤2 together with complete steroid withdrawal and response as a decrease of ≥3 from the baseline score. Results: A total of 142 steroid-dependent UC patients were included in the registry, most of them treated with the Adacolumn™ system. In 69% of patients thiopurine therapy failed to achieve steroid-free clinical remission. Initial clinical remission was obtained in 37% of cases. The initial corticosteroid dose, the number and frequency of apheresis sessions, or the previous failure of thiopurines and/or infliximab did not influence the initial remission rate, but a greater decrease in CRP levels was associated with a higher probability to obtain initial remission. At 6 and 12 months, 41 and 36% of patients were in clinical remission, respectively. Only one serious adverse effect was recorded. Conclusions: In clinical practice, apheresis allows long-term steroid-free clinical remission in up to one third of steroid-dependent UC patients, even in those with prior failure of thiopurines.
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Steroid-sparing strategies in the management of ulcerative colitis: Efficacy of leukocytapheresis.
Manabu Shiraki, Takayuki Yamamoto , World J Gastroenterol. 2012 Nov 7;18(41):5833-8.
Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonpharmacologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is efficacious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treatment of active UC; however, long-term, high doses of corticosteroids usually produce predictable and potentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be minimized. This may be of great benefit to patients because severe side effects of steroids seriously impair health-related quality of life. In this article, we reviewed current evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the management of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-naïve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid-sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, the available data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.
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PWE-236 White cell aphaeresis (WCA) with adacolumn is effective in selected cases of chronic refractory colitis with high histological activity
Premchand P, Ford L, Venkama DPWE-236 White cell aphaeresis (WCA) with adacolumn is effective in selected cases of chronic refractory colitis with high histological activityGut 2012;61:A394.
Introduction Treatment options for patients with chronic refractory colitis are limited. White cell aphaeresis (WCA) is effective in inducing clinical remission in chronic refractory colitis in patients with a strong inflammatory burden at baseline and histologically active disease. Previous multinational sham controlled trials have demonstrated significant improvement when patients with high histological activity (modified Rileys score) are selected for treatment. Methods A prospective study was conducted in 30 patients with severe steroid -dependent or steroid -refractory ulcerative colitis referred for WCA. Inclusion criteria were (i) High disease activity score (partial Mayo score ≥6) (ii) Intractable symptoms despite treatment with steroids and/or immunosuppressants (iii) Severe disease at endoscopy and histologically. The aim was to induce clinical and IBD-Q remission at 12 weeks. A Mayo score ≤3 defined clinical remission. The 32 item Inflammatory Bowel Disease questionnaire (IBD-Q) was used to assess quality of life prior to treatment and at 12 weeks. Results Patient Characteristics: Prior to treatment 28 patients (93.3%) were prescribed 5-ASA compounds. 12 patients (40%) were prescribed topical therapies (5-ASA enemas or suppositories/steroids enemas). 27 patients (90%) were steroid dependent (Prednisolone mean dose 21.1 mg, median 20 mg). Three patients (10%) were steroid refractory (no response to high dose oral steroids). 13 patients (43.3%) were prescribed Azathioprine of the remainder all had documented intolerance or a contraindication. One patient (3.3%) was prescribed six Mercaptopurine. Five patients had failed Infliximab (16.6%) and in one patient (3.3%) it was contraindicated. 1 patient (3.3%) had failed intramuscular Methotrexate. Outcomes: At week 12 clinical remission (Mayo score ≤3) was achieved in 22 patients (73.3%), 18 patients (60%) were no longer prescribed oral steroids. IBD-Q remission at week 12 was achieved in 19 patients (63.3%). Of the remainder, five patients (16.6%) achieved an IBD-Q response. Of eight patients (26.6%) who failed to achieve clinical remission at 12 weeks, one achieved delayed remission at 20 weeks. Of the remaining seven treatment failures, five underwent colectomy (16.6%). Conclusion WCA can be effective in inducing clinical remission and improving quality of life (IBD-Q) indices in chronic severe steroid refractory ulcerative colitis with highly active disease histologically. This data series suggests WCA should be considered before colectomy in this challenging patient group
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Leukocytapheresis in pediatric patients with ulcerative colitis
Takeshi Tomomasa 1, Hitoshi Tajiri, Seiichi Kagimoto, Toshiaki Shimizu, Atsushi Yoden, Kosuke Ushijima, Keiichi Uchida, Hiroaki Kaneko, Daiki Abukawa, Mutsuko Konno, Shun-ichi Maisawa, Takao Kohsaka, Akio Kobayashi, Japanese 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.
efficacy / fecal calprotectin / gma / Leukocytapheresis / moderate / Multicenter / open-label / pediatric / prospective / Safety / steroid refractory / steroid tapering / stool frequency / study / tolerability / ulcerative colitis /
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A multicenter study of the efficacy and safety of leukocytapheresis therapy without concomitant systemic steroid treatment in patients with active ulcerative colitis
Toshifumi Ashida 1, Yutaka Kohgo, Akihiro Munakata, Mitsunori Noguchi, Bunei Iizuka, Yutaka Endo, Hiroyuki Hanai, Toshikazu Yoshikawa, Takayuki Matsumoto, Nobuo Aoyama, Toshiyuki Matsui, Keiichi Mitsuyama, Toshifumi Hibi
We conducted a multicenter study to investigate the efficacy of leukocytapheresis (LCAP) without concomitant steroid therapy in active ulcerative colitis (UC) patients. Twenty patients were enrolled. LCAP was performed twice a week for 3 weeks. The results revealed a significant decrease of the Lichtiger’s clinical activity index (CAI) from 11.7±2.6 at baseline to 6.6±4.1 after the therapy. The endoscopic index and serum C-reactive protein levels also decreased significantly after the therapy. Of the 20 patients, 15 (75%) were assessed as responders (CAI≤4 or ΔCAI≥3), and 7 (35%) achieved complete remission (CAI≤4). No serious adverse reactions were encountered. The results suggest that LCAP is an effective and safe option for patients with active UC who had not received systemic steroid treatment.
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Current and emerging drugs for the treatment of inflammatory bowel disease
John K Triantafillidis, Emmanuel Merikas, and Filippos Georgopoulos Drug Des Devel Ther. 2011; 5: 185–210. doi: 10.2147/DDDT.S11290
During the last decade a large number of biological agents against tumor necrosis factor-α (TNF-α), as well as many biochemical substances and molecules specifically for the medical treatment of patients with inflammatory bowel disease (IBD), have been developed. This enormous progress was a consequence of the significant advances in biotechnology along with the increased knowledge of the underlying pathophysiological mechanisms involved in the pathogenesis of IBD. However, conventional therapies remain the cornerstone of treatment for most patients. During recent years conventional and biologic IBD therapies have been optimized. Newer mesalazine formulations with a reduced pill size and only one dose per day demonstrate similar efficacy to older formulations. New corticosteroids retain the efficacy of older corticosteroids while exhibiting a higher safety profile. The role of antibiotics and probiotics has been further clarified. Significant progress in understanding thiopurine metabolism has improved the effective dose along with adjunctive therapies. Quite a large number of substances and therapies, including biologic agents other than TNF-α inhibitors, unfractionated or low-molecular-weight heparin, omega-3 polyunsaturated fatty acids, microbes and microbial products, leukocytapheresis, and other substances under investigation, could offer important benefits to our patients. In this paper we review the established and emerging therapeutic strategies in patients with Crohn’s disease and ulcerative colitis.
gma / HGF / IL1R / intensive / Leukocytapheresis / leukocyte infiltration / MOA / Refractory patients / Safety / stnf / Tnf-α /
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The Asia-Pacific consensus on ulcerative colitis
Choon Jin Ooi 1, Kwong Ming Fock, Govind K Makharia, Khean Lee Goh, Khoon Lin Ling, Ida Hilmi, Wee Chian Lim, Thia Kelvin, Peter R Gibson, Richard B Gearry, Qin Ouyang, Jose Sollano, Sathaporn Manatsathit, Rungsun Rerknimitr, Shu-Chen Wei, Wai Keung Leung, H Janaka de Silva, Rupert Wl Leong, Asia Pacific Association of Gastroenterology Working Group on Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is increasing in many parts of the Asia-Pacific region. There is a need to improve the awareness of IBD and develop diagnostic and management recommendations relevant to the region. This evidence-based consensus focuses on the definition, epidemiology and management of ulcerative colitis (UC) in Asia. A multi-disciplinary group developed the consensus statements, reviewed the relevant literature, and voted on them anonymously using the Delphi method. The finalized statements were reviewed to determine the level of consensus, evidence quality and strength of recommendation. Infectious colitis must be excluded prior to diagnosing UC. Typical histology and macroscopic extent of the disease seen in the West is found in the Asia-Pacific region. Ulcerative colitis is increasing in many parts of Asia with gender distribution and age of diagnosis similar to the West. Extra-intestinal manifestations including primary sclerosing cholangitis are rarer than in the West. Clinical stratification of disease severity guides management. In Japan, leukocytapheresis is a treatment option. Access to biologic agents remains limited due to high cost and concern over opportunistic infections. The high endemic rates of hepatitis B virus infection require stringent screening before initiating immune-suppressive agents. Vaccination and prophylactic therapies should be initiated on a case-by-case basis and in accordance with local practice. Colorectal cancer complicates chronic colitis. A recent increase in UC is reported in the Asia-Pacific region. These consensus statements aim to improve the recognition of UC and assist clinicians in its management with particular relevance to the region.
asia / consensus / efficacy / gma / GUIDELINES / Leukocytapheresis / procedure / severe / steroid-dependent / steroid-naive / Steroid-refractory / ulcerative colitis /
Scientific corner
Leukocytapheresis in pediatric patients with ulcerative colitis
Takeshi Tomomasa 1, Hitoshi Tajiri, Seiichi Kagimoto, Toshiaki Shimizu, Atsushi Yoden, Kosuke Ushijima, Keiichi Uchida, Hiroaki Kaneko, Daiki Abukawa, Mutsuko Konno, Shun-ichi Maisawa, Takao Kohsaka, Akio Kobayashi, Japanese 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.
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Emerging drugs for the treatment of ulcerative colitis
Luca Pastorelli 1, Theresa T Pizarro, Fabio Cominelli, Maurizio Vecchi Expert Opin Emerg Drugs. 2009 Sep;14(3):505-21. doi: 10.1517/14728210903146882.
Background: Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the colon for which the etiology is currently unknown. At present, strategies to treat UC are primarily targeted to control inflammation during active phases of disease as well as maintain remission during quiescence. As such, several unmet needs in the treatment of UC still remain. In recent years, basic research has led to the recognition of several key factors in the pathogenesis of UC, translating into the development of several novel therapeutic agents. Objective: The aim of this study is to review emerging therapies that may advance the treatment and improve the overall care of UC patients. Methods: An extensive literature search on published manuscripts and meeting proceedings has been performed to provide a comprehensive review of future drug therapies to treat UC. Results/conclusion: The translational application of new discoveries in the basic understanding of UC pathogenesis is continuing and critical for the development of novel treatment strategies. Design of novel biologic therapies to treat UC has the challenge of addressing potential safety issues, while more traditional drugs should be further developed to facilitate patient compliance to treat this chronic, debilitating disease.
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