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Effectiveness of Cytapheresis for Ulcerative Colitis in Special Situations: Delayed Onset of Optimum Efficacy in Elderly Patients

Tomoyoshi Shibuya 1Osamu Nomura 2Kei Nomura 2Koki Okahara 2Keiichi Haga 2Dai Ishikawa 2Naoto Sakamoto 2Tatsuo Ogihara 2Taro Osada 2Akihito Nagahara 2 , Digestion, 2020;101(1):46-52. 

Unlike pharmacologicals, the efficacy of Cytapheresis appears to be time dependent. Accordingly, in the elderly, we observed a delayed response, indicating that elderly patients may respond beyond the end of Cytapheresis therapy. Therefore, patients who do not show efficacy at the end of Cytapheresis therapy should be followed up for delayed response. Further, Cytapheresis is favored by patients for its good safety profile.

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Application of selective leukocytapheresis in the treatment of intractable immune disease

S Rong 1W J Yuan, Zhonghua Yi Xue Za Zhi. 2019 Jan 8;99(2):84-87.

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Efficacy and Safety of Adsorptive Granulocyte and Monocyte Apheresis in Elderly and Pregnant Patients With Ulcerative Colitis

Kazuki Yanagisawa 1Minoru Murakami 2Yuya Kondo 1Shun Oguma 1Shun Kobayashi 1Hiroshi Miyasaka 1Tomoaki Shinohara 3Akihisa Tomori 3Yui Nakano 2Shunichi Furuhata 2Masaya Ikezoe 2 , Ther Apher Dial 2019 Jun;23(3):217-223.

In patients with active ulcerative colitis (UC), adsorptive granulocyte/monocyte apheresis (GMA) is expected to promote remission. We conducted a retrospective cohort study to evaluate the efficacy and safety of GMA in patients with active UC. Twenty‐one UC patients including five pregnant or lactating mothers and four elderly patients (aged >60 years) received up to 10 GMA sessions. UC severity was evaluated at baseline and after GMA therapy according to Lichtiger’s Clinical Activity Index (CAI). We defined clinical remission as CAI ≤4. Overall, the median CAI score after GMA therapy had decreased from 9 to 4 (P < 0.001). The clinical remission rate was 62%, but in the elderly and pregnant or lactating mothers, the remission rates were 100% and 60%, respectively. No severe adverse effects were seen in this study. Our results may support GMA as an effective and safe treatment for active UC patients, including elderly patients and pregnant cases.

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Successful remission of ulcerative colitis flare-up during pregnancy with adsorptive granulomonocytapheresis plus tacrolimus

Tomoyoshi Shibuya 1Keiichi Haga 1Masato Kamei 1Koki Okahara 1Shoko Ito 1Masahito Takahashi 1Osamu Nomura 1Takashi Murakami 1Masae Makino 1Tomohiro Kodani 1Dai Ishikawa 1Naoto Sakamoto 1Taro Osada 1Tatsuo Ogihara 1Sumio Watanabe 1Akihito Nagahara 1 , Intest Res. 2018 Jul;16(3):484-488.

Our experience indicates that GMA, as a non-drug therapeutic intervention with a favorable safety profile, plus tacrolimus might be a relevant treatment option for patients with active IBD during pregnancy. A future study of a large cohort of pregnant patients should strengthen our findings.

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Tu1711 – Safety and Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis in 125 Elderly Patients with Inflammatory Bowel Disease: A Multicenter Cohort Study

Hiroki Tanaka, Satoshi Motoya, Tomoyoshi Shibuya, Satoshi Tanida, Seiichiro Kokuma, Eiji Hosoi Gastroenterology 2018 154 (6) Suppl.S-996–S-997

Background: There are few studies on the usefulness of granulocyte and monocyte adsorptive apheresis (GMA) in elderly patients with inflammatory bowel disease (IBD). We investigated the safety and effectiveness of GMA in elderly patients who participated in the Post-marketing Surveillance Study of GMA Using Adacolumn® for Patients with Inflammatory Bowel Disease Who Have Special Situations (PARTICULAR). Methods: The PARTICULAR study is a retrospective, multicenter cohort study that included patients with ulcerative colitis (UC) or Crohn’s disease (CD) who received GMA between November 2013 and March 2017. Patients with at least one special situation, including elderly patients, patients with anemia, and patients undergoing concomitant treatment with multiple immunosuppressants (IMs) were enrolled. Patients aged # 64 years were excluded from this study. GMA was performed using Adacolumn® (JIMRO, Takasaki, Japan). Each patient received up to a maximum of 11 GMA sessions. The safety of GMA was assessed in all patients. The effectiveness of GMA was assessed in patients with UC with a partial UC disease activity index (pUC-DAI) score of $ 3. Remission was defined as a pUC-DAI score of # 2. Patients receiving concomitant treatment with infliximab, adalimumab, or calcineurin inhibitors were excluded from the effectiveness assessment. The incidence of adverse events (AEs) and remission rates were compared between elderly patients with and without any special situation using univariate and multivariate logistic regression analysis. Results: A total of 125 elderly patients (118 UC, 7 CD) from 93 institutions were included. The median age was 73.2 years. Fifty-six patients did not have any special situation, and 69 had at least one or more special situations. The incidence of AEs was 11.2% in all patients. The incidence of AEs was significantly lower in elderly patients without any special situation (3.6%) than in those with at least one or more special situations (17.4%) (Figure 1A). AEs significantly occurred in elderly patients with anemia (21.9%) and on multiple concomitant IMs (23.8%) compared to those without any special situation (3.6%). Anemia and multiple concomitant IMs were identified as independent predictors for a higher incidence of AEs (Table 1). The effectiveness of GMA was assessed in 92 patients with UC. The remission rate was 48.9%. No difference was observed in the remission rate between elderly patients without any special situation (52.2%) and those with at least one or more special situations (45.7%) (Figure 1B). Conclusions: A low incidence of AEs (3.6%) was found in elderly IBD patients receiving GMA without any special situation. Remission was achieved by GMA in 48.6% of the elderly UC patients. Care should be taken when using GMA in elderly IBD patients with anemia or on multiple concomitant IMs

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Changes in Treatment with Granulocyte and Monocyte Adsorptive Apheresis from the Past to Future in Patients with Inflammatory Bowel Disease

Shingo KatoAkira IshibashiKaori SugiuraKazuhito KaniTomonari OgawaHajime HasegawaKoji Yakabi, Contrib Nephrol 2018;196:200-208.

GMA decreases inflammatory cytokines and upregulates regulatory T cells. Intensive GMA is significantly more effective than weekly GMA in patients with IBD. The frequency of GMA sessions per week positively correlates with treatment effects. GMA can be safely used in pregnant women and children because of its low adverse event rates. Maintenance therapy and rescue therapy for loss of response of anti-tumor necrosis factor (TNF)-α antibodies are effective. Optimal patients who responded to combination therapy with infliximab and GMA showed aggravation characteristics against infliximab treatment at week 4. Key Message: Prospective randomized blinded studies using a sham column should be performed for the loss of response against anti-TNF-α antibodies.

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Efficacy and safety of granulocyte adsorption apheresis in elderly patients with ulcerative colitis.

Ayumi Ito 1Teppei Omori 1Norio Hanafusa 1Ken Tsuchiya 1Shinichi Nakamura 1Katsutoshi Tokushige 1 , J Clin Apher. 2018 Aug;33(4):514-520.

Background: Elderly ulcerative colitis (UC) is increasing. Elderly UC differ from younger UC with respect to the course of their disease. Granulocyte adsorption apheresis (CAP) is often used to treat elderly UC. We retrospectively analyzed the cases of elderly UC who underwent CAP for remission induction therapy in a comparison with younger UC. Methods: 96 patients with UC underwent CAP. Patients who concurrently received tacrolimus, biological agents, or high-dose steroid therapy were excluded. The remaining 80 patients were evaluated. We divided them into an elderly group (aged ≥65 years) and a younger group, and then we compared the groups’ (1) clinical characteristics, (2) the efficacy and adverse effects of CAP, and (3) the complications of PSL. Results: The remission rate was 70.8% in the elderly group and 87.5% in the younger group. There were significant differences between the two groups with respect to the age at the onset of UC, the estimated glomerular filtration rate on admission, underlying diseases, and complications of PSL therapy. Adverse effects of CAP included headache, complications of blood reinfusion, heparin allergy, hypotension, and failure of blood removal. There were significant differences between the two groups with respect to the complications of PSL therapy (all P < .05). Conclusions: Although the elderly group had longer durations of UC, a higher prevalence of underlying diseases, and a higher frequency of adverse events due to PSL therapy, no serious adverse effects of CAP occurred in either group. Thus, CAP was safe and effective in both younger and elderly UC.

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Effects of Granulocyte and Monocyte Adsorptive Apheresis in Renal Transplantation Recipients With Concomitant Cytomegalovirus Infection.

T Naganuma 1Y Takemoto 2T Iwai 2N Kuwabara 2J Uchida 2T Nakatani 2K Kitamura 3A Masuda 3K Ohmori 4M Matsuura 5H Nakase 5 , Transplant Proc. 2016 Apr;48(3):929-32.

This case series found that GMAA in combination with antiviral drugs may shorten the duration of treatment against CMV infection in renal transplant recipients. Further studies in a larger number of patients are required to confirm these results.

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Case of generalized pustular psoriasis with end-stage renal disease successfully treated with granulocyte monocyte apheresis in combination with hemodialysis.

Tomotaka Mabuchi 1Yasuaki ManabeHanako YamaokaTami OtaMasayuki KatoNorihiro IkomaYoshiyuki KusakabeHirotaka KomabaAkira Ozawa, J Dermatol. 2014 Jun;41(6):521-4.

 During maintenance HD twice a week, weekly GMA was started at Tokai University Hospital. The skin symptoms disappeared after five administrations of GMA. We suggest that GMA is an effective therapy for GPP patients with ESRD who are treated with HD.

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Ulcerative colitis-associated pulmonary nodules with cavity formation successfully treated with mesalazine and granulocyte-monocyte apheresis.

Hiroaki Nomoto 1Yoshikazu HayashiSatoshi ShinozakiTomonori YanoKeijiro SunadaWataru SasaoAya KitamuraMai OhashiShuhei HiyamaAlan Kawarai LeforHironori Yamamoto, Clin J Gastroenterol 2014 Dec;7(6):476-80.

UC-associated pulmonary lesions can be treated without steroid administration, and we suggest that this strategy is an option for a patient with UC-associated pulmonary lesions that cannot be differentiated from an infection.

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