Yuki Noguchi 1, Keiji Shimazu 2, Teruhiko Totani 1, Kazumasa Komura 3, Atsuo Tanaka 2
Comparison of adsorption efficiency of leukocytes in single needle GMA with or without PSL treatment in patients with active ulcerative colitis
Granulocyte monocyte adsorption (GMA) is considered one of the modalities for the remission induction of ulcerative colitis (UC). We previously reported that single-needle GMA (SN-GMA) could simplify the GMA. In the present study, the efficiency of SNGMA was examined according to the administration of corticosteroids (PSL) in UC patients. Blood sample were taken at proximal and distal side of the column during the SN-GMA treatment. Disease activity score (partial Mayo score: pMayo score) before and after the SN-GMA was investigated. The data of 18 patients with active UC (11 and 7 patients with PSL naïve and PSL use groups, respectively) treated with SN-GMA was analyzed. The mean pMayo score before the GMA treatment was comparable between the PSL naïve group (p = 0.26), whereas the score after the GMA treatment was significantly lower in PSL naïve group (0.8 + 0.6) than in PSL use group (3.0 + 2.1) (p = 0.04). Patients achieving the clinical remission were more observed in the PSL naive group (90.9%) than in the PSL use group (42.9%) (p = 0.047). The adsorption efficiency in the PSL naïve and PSL use groups were as follows: leukocytes (34.45 ± 7.43% vs 23.14 ± 7.56%: p = 0.008), granulocytes (41.74 ± 10.07% vs 27.99 ± 15.11%: p = 0.04), monocytes (32.59 ± 24.07% vs 33.16 ± 24.18%: p = 0.95), and lymphocytes (-1.87 ± 18.17% vs -3.79 ± 22.52%: p = 0.84), with a significant difference of the absorption efficiency in leukocytes and granulocytes. These data collectively indicate that the SN-GMA can be applied for the remission induction to active UC patients with a higher clinical remission rate in PSL naïve patients compared to PSL use patients.
Induction of mucosal healing by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids in patients with ulcerative colitis: long-term remission maintenance after induction by GMA and efficacy of GMA re-treatment upon relapse
Takumi Fukuchi , Kousaku Kawashima , Hideaki Koga , Ran Utsunomiya, Kohei Sugiyama , Keiji Shimazu , Takaaki Eguchi , Shunji Ishihara J Clin Biochem Nutr. 2022 Mar;70(2):197-204. doi: 10.3164/jcbn.21-112. Epub 2021 Dec 25.
This study examined the long-term maintenance rate after inducing remission by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids (CS) and GMA re-treatment efficacy in the same patients upon relapse with ulcerative colitis. Patients who achieved clinical remission and mucosal healing (MH) by first-time intensive GMA (first GMA) without CS were enrolled. The cumulative non-relapse survival rate up to week 156 was calculated. Patients with relapse during the maintenance period underwent second-time intensive GMA (second GMA) without CS. Clinical remission and MH rates following second GMA were compared to those following first GMA in the same patients. Of the 84 patients enrolled, 78 were followed until week 156 and 34 demonstrated relapse. The cumulative non-relapse survival rate by week 156 was 56.4%. Clinical remission and MH rates after second GMA did not differ from those after first GMA in the same patients (week 6: clinical remission, 100% vs 88.4%, p = 0.134; MH, 100% vs 84.8%, p = 0.074). In conclusion, MH induction by intensive GMA without use of CS in ulcerative colitis patients contributes to subsequent long-term clinical remission maintenance. GMA re-treatment efficacy was comparable to that of first GMA in the same patients who had relapse.
Granulocytapheresis in ulcerative colitis (in Spanish)
Gerardo Prieto Bozano an. pedatr. contin.2012;10(5):286-9
- Existen 2 dispositivos de granulocitoféresis: Cellsorba® (fibras de poliéster no tejidas), que fija granulocitos y linfocitos, y Adacolumn® (acetato de celulosa) que fija selectivamente granulocitos y monocitos.
- Además de retirar leucocitos activados, la aféresis produce incremento del número de granulocitos CD10-negativos (inmaduros), disminución de citocinas proinflamatorias (factor de necrosis tumoral alfa [TNF-α], interleucina [IL-6],IL-8 e IL-1β) e incremento de citocinas inhibitorias (IL-1, IL-10)
- La granulocitoféresis es un método razonablemente eficaz y seguro para obtener la remisión en niños con colitis ulcerosa corticodependiente o resistente, sobre todo en pacientes en el primer episodio, en enfermedad de corta evolución y en aquellos que no han recibido esteroides
- El procedimiento requiere 2 accesos venosos de buen flujo. La pauta más habitual de tratamiento consiste en 1–2 sesiones semanales de 60min a un flujo de 30ml/min, hasta un total de 5–10 sesiones
Apheresis in Inflammatory Bowel Disease: Current Evidence
Daniel Vasile Balaban and Mariana Jinga Crohn’s Disease Recent Advances book, October 15th, 2020 DOI: 10.5772/intechopen.93605
Inflammatory bowel diseases (IBD) have become a major focus for gastroenterologists worldwide, with the increasing incidence and complexity of cases, which pose therapeutic challenges. Currently available approaches fail in controlling the disease activity in a significant proportion of patients and some of the therapies are associated with significant adverse events. Although new molecules are on the horizon and treatment strategies have been optimized, novel therapeutic tools are much needed in IBD for patients who fail to attain control of the disease. Apheresis is now a common non-pharmacological therapeutic modality used in several pathologies, IBD also. In the current review, we summarize currently available evidence with respect to selective apheresis in IBD.
Factors associated with the outcomes in ulcerative colitis patients undergoing granulocyte and monocyte adsorptive apheresis as remission induction therapy: A multicenter cohort study
Yoh Ishiguro 1, Toshihide Ohmori 2, Ken Umemura 3, Masahiro Iizuka 4 ,Ther Apher Dial 2020 Oct 7.
GMA was an effective treatment for corticosteroid-naïve patients and the efficacy sustained longer in those not receiving immunomodulators during GMA. GMA fulfills the notion that apheresis is to induce disease remission by removing from the body factors known to perpetuate disease. In therapeutic settings, these findings should help better decision making and avoid futile use of medical resources.
A multicenter retrospective study aiming to identify patients who respond well to adsorptive granulomonocytapheresis in moderately to severely active ulcerative colitis.
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.
Efficacy and usefulness of new single-needle Intensive granulocyte and monocyte adsorptive apheresis in active ulcerative colitis patients without corticosteroids and biologics
Keiji Shimazu 1, Takumi Fukuchi 2, Insung Kim 3, Yuki Noguchi 3, Megumi Iwata 1, Shintaro Koyama 2 4, Satoshi Ubukata 2, Atsuo Tanaka 1 , Ther Apher Dial 2016 Aug;20(4):383-9.
Intensive granulocyte and monocyte adsorptive apheresis (GMA) twice weekly is effective and safe for patients with active ulcerative colitis (UC), but the requirement for maintaining two blood access routes is problematic. Here we compared the efficacy and safety of one-route blood access intensive GMA using a single-needle (SN) and conventional two-route blood access intensive GMA using a double-needle (DN) in patients with active UC not undergoing corticosteroid therapy. Among 80 active UC patients, 38 patients received SN intensive GMA and 42 patients received DN intensive GMA. The clinical remission ratio and mucosal healing ratio at 6 weeks, and the cumulative non-relapse ratio at 52 weeks did not differ significantly between groups. In addition, no serious or mild adverse effects were observed in SN intensive GMA. SN intensive GMA may be an adequate and novel therapeutic option for active UC as an alternative therapy before using corticosteroids.
Therapeutic effect of intensive granulocyte and monocyte adsorption apheresis combined with thiopurines for steroid- and biologics-naive Japanese patients with early-diagnosed Crohn’s disease.
Takumi Fukuchi, Hiroshi Nakase 1, Satoshi Ubukata, Minoru Matsuura, Takuya Yoshino, Takahiko Toyonaga, Keiji Shimazu, Hideaki Koga, Hiroshi Yamashita, Dai Ito, Kiyoshi Ashida, BMC Gastroenterol. 2014 Jul 11;13:124.
Combination therapy with intensive GMAA and thiopurines administration rapidly induced high remission in patients with active early-diagnosed CD without serious adverse effect. Mucosal healing was observed in 50.0% of enrolled patients. This combination therapy might be a rational option for patients with early-diagnosed CD.
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.
Mucosal healing of esophageal involvement of Crohn’s disease with granulocyte/monocyte adsorption
Kosaku Moribata 1, Jun Kato, Sae Iimura, Satoshi Yoshida, Naoki Shingaki, Kazuki Ueda, Hisanobu Deguchi, Izumi Inoue, Takao Maekita, Mikitaka Iguchi, Hideyuki Tamai, Masao Ichinose, J Clin Apher. 2011;26(4):225-7.
We report a case of a 16-year-old male who suffered from Crohn’s disease (CD) with esophageal involvement, showing remarkable improvement with granulocyte/monocyte adsorption (GMA). The patient had been diagnosed as ileocolic CD and was treated with 5-aminosalicylate. He was admitted to our hospital with symptoms of fever, diarrhea, and odynophagia. Endoscopic examinations revealed that the exacerbation of ileocolic ulcers, and advent of ulcers in esophagus. Because of the patient’s refusal to receive corticosteroids, immunomodulators, or biologics, he underwent GMA twice a week. After 10 sessions of GMA, he entered remission with significant decrease in clinical activity. In addition, endoscopic examinations showed remarkable improvement of ileocolic ulcers and disappearance of esophageal lesions. No adverse events were observed. GMA could be effective for manifestations of CD in gastrointestinal tract other than ileum or colon.
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