Satoshi Tanida ^1 2, Naoto Imura ², Shun Sasoh ², Yoshimasa Kubota ², Tesshin Ban ², Tomoaki Ando ², Makoto Nakamura ², Takashi Joh ²

J Clin Med Res  2025 Apr;17(4):240-246. doi: 10.14740/jocmr6188. Epub 2025 Apr 5.

Case 1 involved a 34-year-old woman who had been diagnosed with Crohn’s disease (CD) at 30 years old. After deciding to discontinue CD treatment, she was diagnosed with moderate flare-up of CD based on disease activity and endoscopic findings. Inadequate response was seen 7 days after starting oral prednisolone (PSL) at 30 mg/day, so combination therapy was started with intensive granulocyte and monocyte adsorptive apheresis (GMA) plus upadacitinib (UPA) at 45 mg/day. Twelve weeks after starting this combination therapy, clinical remission and endoscopic and histological improvements of the inflamed mucosa were achieved with no adverse events. Case 2 involved a 26-year-old man who had been diagnosed with CD at 13 years old. He was diagnosed with severe flare-up of CD based on disease activity and endoscopic findings due to loss of response to double doses of infliximab (IFX). Combination therapy was started with intensive GMA plus UPA at 45 mg/day. Twelve weeks after starting this therapy, clinical remission and endoscopic and histological improvements of the inflamed mucosa were achieved with no adverse events. The combination of intensive GMA plus UPA appears to have provided an effective therapeutic option for refractory CD in a patient with a 4-year history of CD and refractoriness to systemic corticosteroids, and in another patient with a 13-year history of CD and loss of response to IFX.

Ryosuke Kasuga 1, Po-Sung Chu 1, Nobuhito Taniki 1, Aya Yoshida 1, Rei Morikawa 1, Takaya Tabuchi 1, Fumie Noguchi 1, Karin Yamataka 1, Yukie Nakadai 1, Mayuko Kondo 1, Hirotoshi Ebinuma 1 2, Takanori Kanai 1, Nobuhiro Nakamoto 1

Background: Patients with severe alcohol-associated hepatitis (SAH) have a high short-term mortality rate. Unmet needs exist in patients who are refractory to corticosteroids (CS) or are ineligible for early liver transplantation.

Methods: This was a prospective, open-label, nonrandomized pilot study conducted at a liver transplant center in Tokyo, Japan, starting in October 2015. Lille model and Model for End-stage Liver Disease (MELD) score-defined CS nonresponsive or CS-intolerant patients with SAH who fulfilled the inclusion criteria (leukocytosis over 10,000/μL, etc.) were considered for enrollment. The median duration from admission to enrollment was 23 days (IQR, 14-31 days), after standard of care. Granulocyte-monocyte/macrophage apheresis (GMA) performed with Adacolumn twice per week, up to 10 times per treatment course, was evaluated.

Results: 13 GMA treatments were conducted through December 2021. Maddrey Discriminant Function was 53.217.7 at admission. The overall survival rate was 90.9% at 90 and 180 days. MELD scores significantly improved, from median (IQRs) of 23 (20-25) to 15 (13-21) after GMA (p<0.0001). Estimated mortality risks using the Lille model and MELD scores significantly improved from 20.9%±16.5% to 7.4%±7.3% at 2 months and from 30.4%±21.3% to 11.6%±10.8% at 6 months, respectively (both p<0.01), and were internally validated. The cumulative rate of alcohol relapse was 35.9% per year. No severe adverse events were observed. In exploratory analysis, granulocyte colony-stimulating factor levels were significantly correlated with prognostic systems such as MELD-Sodium scores after GMA (correlation coefficient= -0.9943, p<0.0001) but not before GMA (p=0.62). Conclusions: Compared to published studies, GMA is associated with a lower-than-expected 90- and 180-day mortality in patients with CS-nonresponsive or CS-intolerant SAH. GMA may meet the needs as a salvage anti-inflammatory therapy for SAH. (Trial registration: UMIN000019351 and jRCTs No.032180221) (274 words).

N.D. Salazar Parada1, M. Algara San Nicolas1,A. Suárez-Saro Fernández1, A. Masedo1, C. Yela San Bernardino1,C. Begoña1, P. Martínez Montiel1, I. Fernández Vázquez1

UEG journal 2023 SUPPLEMENT ABSTRACT UEG Week 2023 Poster Presentations 15 October 2023 page 1047

Introduction: Despite the importance of granulocytoapheresis (GCA) in the treatment of inflammatory bowel disease (IBD), its effectiveness in steroid-dependent and steroid-refractory IBD has not been widely evaluated, the approaches are heterogeneous and data on efficacy and safety remain limited in our population.
Aims & Methods: This study aims to assess the effectiveness of GCA for induction of remission and maintenance in patients with steroid-dependent and steroid-refractory IBD in the real-world practice.
Retrospective cohort of patients with steroid-dependent and steroid-refractory colonic IBD, in which GCA was used as induction of remission and maintenance treatment between January-2015 to January-2023. We
analyze demographics, disease characteristics, prior exposure including biologic agents. The success of GCA was defined on a decrease of at least 3 points in the True-love score for Ulcerative Colitis (UC) and a decrease of
at least 100 points in the CDAI for Crohn Disease (CD). To analyze predictive factors of treatment success we performed a univariate and multivariable analysis.
Results: 49 patients were included. 5 cycles of apheresis were performed in the first 3 weeks as induction and at least 10 cycles of apheresis as maintenance in the next 6 months.

75 % (37 / 49) had UC, 86.4 % (32 / 37) were steroid-refractory while 13.6 % (5 / 37) steroid-dependent, 54 % (20 / 37) male; median age 60 ± 10.5 years with a mean of 10.5 years from diagnosis. 67.7 % (25 / 37) had received at least 1 biological treatment in the past, 43.5 % (17 / 39) ≥ 2 biological. After induction, 75 % (28 / 37) responded to treatment, 62 % (23 / 37) continued with maintenance therapy of which 67 % (15 / 23) responding. Mean PCR and calprotectin were 3,16 mg / dl and 2038 mg / dl before treatment, 1.45mg / dl and 1025 mg / dl after induction, 1.15 mg / dl and 900 mg / dl after maintenance, respectively.

25 % (12 / 49) had CD, 50 % (6/12) male; median age 62 ± 9.8 years, 75% (9 / 12) steroid-refractory and 25 % (3 / 12) steroid-dependent, with a mean of 9 years from diagnosis, 67.7 % had received at least one biological
treatment in the past. After induction, 58 % (7 / 12) responded, 80 % (10 /12) continued with maintenance with 50 % (5 / 10) responding. Mean CRP and calprotectin were 3.16 mg / dl and 3645 mg / dl before treatment, 1.7
mg / dl and 2473 mg / dl after induction, 1.14 mg / dl and 623 mg / dl after maintenance.
Factors such as smoking, extent of disease, longer disease course and lack of response to previous treatments, were not significantly related to response in either induction or maintenance.
No patient had major adverse events recorded.
Conclusion: GCA appears to be safe and effective for inducing and maintaining clinical remission in patients with IBD, especially in patients with UC. No significant differences were found in disease extension, duration or
lack of response to previous treatments.

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

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.

Multicenter prospective study for clinical and endoscopic efficacies of leukocytapheresis therapy in patients with ulcerative colitis – PubMed (nih.gov)

Multicenter prospective study for clinical and endoscopic efficacies of leukocytapheresis therapy in patients with ulcerative colitis: Scandinavian Journal of Gastroenterology: Vol 48, No 4 (tandfonline.com)

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.

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

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