Mariko Seishima
Tag: Clinical remission
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SY5-01 Granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis
poster at ISFA 2019 pag 57
Generalized pustular psoriasis (GPP) is a rare inflammatory skin disorder characterized by a fever, edema, and generalized erythema with neutrophilic pustules. It sometimes occurs in the course of psoriasis vulgaris, or develops suddenly without any history of psoriasis. Mutations of the IL36RN (deficiency of interleukin thirty-six receptor antagonist: DITRA), CARD14 and AP1S3 genes underlie monogenic auto-inflammatory disorders causing GPP. GPP patients are usually treated with oral administration of etretinate, cyclosporine, and metrexate, biologics including TNF α inhibitors, antibodies to IL-17, IL-17 receptor, and IL-23 p19, and granulocyte and monocyte adsorption apheresis (GMA). Cyclosporine, TNF α inhibitors, and GMA are used for GPP in pediatric, pregnant, or lactating patients. GMA is an extracorporeal apheresis that removes activated granulocytes and monocytes using a column packed with cellulose acetate beads. Multicenter study was performed to access efficacy of selectively depleting the myeloid lineage leukocytes in GPP patients. Fifteen patients with persistent moderate to severe GPP despite conventional therapy were included. Based on the GPP severity scores relative to entry, the overall scores improved, and the area of erythroderma, pustules, and edema decreased. Likewise, Dermatology Life Quality Index (DLQI) improved, reflecting better daily function and quality of life. Twelve out of 14 patients were judged as responders (85.7%), and 10 out of 12 patients maintained the clinical response for10 weeks after the last GMA session without any change in medication. Thus, GMA is estimated to be safe and effective, suggesting a major role of granulocytes/ monocytes in the immunepathogenesis of GPP. Recent study showed that GMA was effective for 100% of DITRA patients and for 64.7% of the patients with IL36RN mutation-negative GPP. Thus, GMA is effective therapy for both DITRA and non-DITRA GPP patients. GMA may be a useful therapy for all GPP patients
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SY4-03 The efficacy of combination therapy of intensive GMA with biologics or a JAK inhibitor for refractory inflammatory bowel disease
Satoshi Tanida
poster at ISFA 2019 pag 56
Background and Aim: A monotherapy with intensive GMA, biologics or a JAK inhibitor are limited in patients with intractable Crohn’s disease (CD) or ulcerative colitis (UC). We retrospectively evaluated the 10- and 52-week efficacy and safety of combination therapy of intensive GMA with biologics or a JAK inhibitor for intractable UC or CD.
Method: A combination of intensive GMA (2 sessions a week, total 10 times) with tofacitinib (TOF) for active UC was performed and that of intensive GMA with ustekinumab (UST) for active CD was done. Results: Of 6 consecutive UC patients receiving a combination therapy of TOF (20 mg daily for 8 weeks as induction therapy and subsequently 10 mg daily) plus intensive GMA for moderately-to-severely active UC and loss of response to corticosteroids, azathioprine, and/ or biologic therapies, 67% (4 cases) displayed clinical remission according to Mayo score and 100% displayed mucosal healing at 10 weeks. A temporary increase in CPK were seen. Of 5 consecutive CD patients receiving a combination therapy of ustekinumab (every 8 weeks) plus intensive GMA for moderately-to-severely active CD and loss of response to corticosteroids, azathioprine, and/or biologic therapies, 75% displayed cumulative steroid-free clinical remission at 10 weeks and did such remission over 52 weeks under subsequent maintenance monotherapy of UST. The mean CDAI at baseline were 257. Its values at 10 and 52 weeks after the combination therapy with UST plus intensive GMA were 48 and 68, respectively. One case showed mucosal healing at 52 weeks according to SES-CD. No adverse events were observed. Conclusions: Combination therapy of intensive GMA with biologics or a JAK inhibitor appeared to be effective and safe for refractory UC or CD.
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SY3-04 Real-world experiences of cytapheresis therapy for ulcerative colitis; results from large-scale multicenter observational studies
Taku Kobayashi
poster at ISFA 2019 pag 53
There are two types of extracorporeal therapy for treating active ulcerative colitis (UC), granulocyte and monocyte adsorption (GMA) and leukocytapheresis (LCAP). Although Sawada et al reported the efficacy of LCAP by the randomized controlled trial (Sawada K et al. Am J Gastroenterol 2005), the larger sham-controlled multicenter trial of GMA failed to prove its efficacy (Sands BE et al. Gastroenterol 2008). Therefore, evidence to show their efficacy relies more on the real-world data, including the post-marketing surveillance (PMS). The large-scale PMS for LCAP was named as REFINE study, involving 847 patients from 116 medical facilities in Japan (Yokoyama Y, Kobayashi T et al. J Crohn Colitis 2014). Adverse events were seen only in 10.3% and the vast majority were mild. The overall clinical remission rate was 68.9%, and the mucosal healing rate was 62.5%. These results were very consistent with the results from PMS of 697 patients treated with GMA, which also demonstrated its real-world effectiveness and safety (Hibi T et al. Dig Liver Dis 2008). In addition, a retrospective observational study aimed to evaluate the clinical outcome at 1 year and identify risk factors for relapse after LCAP was recently conducted among patients who had achieved remission in the PMS (Kobayashi T et al. J Gastroenterol 2018). The 1-year cumulative relapse free rate was 63.6%. Following LCAP, a high clinical activity and a high leukocyte count were associated with a greater risk of relapse. Intensive LCAP was associated with favorable long-term outcomes in corticosteroidrefractory patients. The response rate of re-treatment upon relapse was as high as 85%. These results on the risks of relapse as well as effectiveness of re-treatment may help to overcome the weakness of cytapheresis therapy in maintaining remission. Results from the clinical trial evaluating the clinical efficacy of intermittent maintenance cytapheresis therapy are also warranted.
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Regain of Response to Adalimumab in a Steroid-Dependent Pediatric Patient With Ulcerative Colitis After Undergoing Selective Granulocyte and Monocyte Apheresis.
Marta Velasco Rodríguez-Belvís 1, Javier Francisco Viada Bris 1, Laura Palomino Pérez 1, Rosa Ana Muñoz Codoceo 1 , inflamm Bowel Dis. 2019 Jun 18;25(7):e82-e83.
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Single-Needle Intensive Granulocyte and Monocyte Adsorptive Apheresis Is Suitable for Elderly Patients With Active Ulcerative Colitis Taking no Corticosteroids or Biologics
Takumi Fukuchi 1, Hideaki Koga 1, Shinji Kaichi 1, Akira Ishikawa 2, Takahisa Horita 3, Ryota Araki 4, Atsushi Yokota 5, Yukiomi Namba 6, Masahiro Kyo 7, Takaaki Eguchi 8, Keiji Shimazu 9 Ther Apher Dial 2019 Jun;23(3):224-232
Single-needle intensive granulocyte/monocyte adsorptive apheresis might be a novel alternative therapeutic option for elderly ulcerative colitis patients before considering corticosteroids.
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Granulomonocytapheresis as a cell-dependent treatment option for patients with inflammatory bowel disease: Concepts and clinical features for better therapeutic outcomes.
Abbi R Saniabadi 1, Tomotaka Tanaka 2, Takayuki Yamamoto 3, Wolfgang Kruis 4, Rodolfo Sacco 5 , J Clin Apher 2019 Feb;34(1):51-60.
Accordingly, for responder patients, GMA fulfills a desire to be treated without drugs.
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Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn’s and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition
Dan Turner 1, Frank M Ruemmele 2, Esther Orlanski-Meyer 1, Anne M Griffiths 3, Javier Martin de Carpi et al. J Pediatr Gastroenterol Nutr. 2018 Aug;67(2):257-291. doi: 10.1097/MPG.0000000000002035.
Background: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. Methods: These guidelines are a joint effort of the European Crohn’s and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. Results: These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. Conclusions: These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.
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Shorter Relapse-Free Period after Leukocyte Removal Therapy in Younger than Older Patients with Ulcerative Colitis
Satoko Yamasaki 1, Yasuhisa Sakata 2, Hisako Yoshida 3, Sinpei Shirai 1, Yuichiro Tanaka 1, Ryo Nakano 1, Takahiro Yukimoto 1, Nanae Tsuruoka 1, Ryo Shimoda 1, Makoto Fukuda 1, Motoaki Miyazono 1, Yuji Ikeda 1, Ryuichi Iwakiri 1, Keizo Anzai 1, Kazuma Fujimoto 1 , Digestion. 2019;100(4):247-253.
Background: Leukocyte removal therapy (LRT) is an effective treatment for active ulcerative colitis (UC). The present study was performed to evaluate the relapse-free period after LRT and identify risk factors for relapse. Methods: In total, 94 patients who underwent first-time LRT for remission of moderate to severe UC from April 2004 to March 2016 were enrolled in the present study. The patients were randomly assigned to one of 2 treatments: leukocytapheresis (LCAP; n = 43) or granulocyte and monocyte/macrophage adsorptive apheresis (GMA; n = 51). The 5-year cumulative relapse-free rate and risk factors for relapse were evaluated. Results: The therapeutic response rate was 82% for GMA and 70% for LCAP without a statistically significant difference. The 5-year relapse-free rate was 34.7% in the LRT group. The 5-year relapse-free rate in patients aged > 40 years was 49.9%, which was significantly higher than that in patients aged ≤40 years (22.9%, p < 0.01). The relapse-free period was longer in the older than younger patients. The relapse-free period was longer in the ≥40- than <40-year-old patients (1,197 vs. 441 days, respectively; p = 0.03). Conclusions: The relapse-free period after LRT was examined in patients with UC, and 34.7% of patients achieved clinical remission within a 5-year period. The risk factor for early relapse after LRT was younger age. In conclusion, LRT might be a therapeutic option for maintenance of remission in patients with UC, especially patients aged ≥40 years.
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A multicenter retrospective study aiming to identify patients who respond well to adsorptive granulomonocytapheresis in moderately to severely active ulcerative colitis.
https://pubmed.ncbi.nlm.nih.gov/29977035/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033883/pdf/41424_2018_Article_37.pdf
Takayuki Yamamoto 1, Takayuki Iida 2, Kentaro Ikeya 2, Masaichi Kato 2, Ai Matsuura 2, Satoshi Tamura 3, Ryosuke Takano 3, Shinya Tani 4, Satoshi Osawa 4, Ken Sugimoto 3, Takahiro Shimoyama 5, Hiroyuki Hanai 2 , Clin Transl Gastroenterol 2018 Jul 6;9(7):170.
Objectives: Adsorptive granulomonocytapheresis (GMA) with the Adacolumn has been introduced as a non-pharmacologic treatment for ulcerative colitis (UC). However, a subset of patients who might respond well to GMA needs to be targeted. This study was conducted at three IBD centers to determine factors affecting the efficacy of GMA in patients with moderately-to-severely active UC. 1234567890(); 1234567890(),; 1234567890(); 1234567890(); Methods: From January 2008 to December 2017, a total of 894 active episodes (first attack or relapse) in 593 patients were treated with GMA. Clinical remission was defined as normal stool frequency and no rectal bleeding. Multiple clinical and laboratory parameters at entry were considered for efficacy assessment. Results: Clinical remission was achieved during 422 (47%) of the 894 treatment cases. In the multivariate analysis, predictors for favorable response to GMA were age ≤60 years, UC duration <1 year, Mayo endoscopic subscore 2 (vs. 3), steroid naïve UC, and biologic naïve UC. Clinical remission rate was 70% in patients with four of the five factors, 52% in patients with three factors, 46% in patients with two factors, 39% in patients with one factor, and 18% in patients with none of these factors. Overall, the clinical remission rate was significantly higher in patients with a greater number of the five predictors (P < 0.0001). Conclusions: GMA appeared to be effective in steroid naïve and biologic naïve patients with short duration of UC. Elderly patients (>60 years) and those with severe endoscopic activity did not respond well to GMA. Additional, well designed, prospective, controlled trials should strengthen our findings.
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A systems pharmacology model for inflammatory bowel disease
https://pubmed.ncbi.nlm.nih.gov/29513758/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841748/pdf/pone.0192949.pdf
Violeta Balbas-Martinez 1 2, Leire Ruiz-Cerdá 1 2, Itziar Irurzun-Arana 1 2, Ignacio González-García 1, An Vermeulen 3 4, José David Gómez-Mantilla 1, Iñaki F Trocóniz 1 2 , PLoS One. 2018 Mar 7;13(3):e0192949. doi
In this article, we propose a logic model for Inflammatory Bowel Disease (IBD) which consists of 43 nodes and 298 qualitative interactions. The model presented is able to describe the pathogenic mechanisms of the disorder and qualitatively describes the characteristic chronic inflammation. A perturbation analysis performed on the IBD network indicates that the model is robust. Also, as described in clinical trials, a simulation of anti-TNFα, anti-IL2 and Granulocyte and Monocyte Apheresis showed a decrease in the Metalloproteinases node (MMPs), which means a decrease in tissue damage. In contrast, as clinical trials have demonstrated, a simulation of anti-IL17 and anti-IFNγ or IL10 overexpression therapy did not show any major change in MMPs expression, as corresponds to a failed therapy. The model proved to be a promising in silico tool for the evaluation of potential therapeutic targets, the identification of new IBD biomarkers, the integration of IBD polymorphisms to anticipate responders and non-responders and can be reduced and transformed in quantitative model/s.
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