Masaki Kato ¹, Masaki Yamashita ¹, Shigeki Kojima ², Mitsuto Tsukui ¹, Yoshihiko Iijima ¹, Kenichi Araki ¹, Jun Ishida ¹, Takumi Komatsu ¹, Yusuke Nakamoto ¹, Akiyo Kawashima ¹, Maki Konno ¹, Hirofumi Kiyokawa ¹, Yoshinori Sato ¹, Tsutomu Sakurada ², Tadateru Maehata ¹, Hiroshi Yasuda ¹, Keisuke Tateishi ¹

Medicine (Baltimore). 2025 Aug 1;104(31):e43389. doi: 10.1097/MD.0000000000043389.

5-Aminosalicylate (5-ASA) intolerance complicates ulcerative colitis (UC) management, often necessitating alternative treatment approaches. Granulocyte and monocyte adsorptive apheresis (GMA) has been recognized as a safe treatment option for patients with UC who are refractory or intolerant to conventional drugs, including steroids; however, its effectiveness and safety in patients with 5-ASA intolerance remain unclear. This study aimed to investigate the effectiveness and safety of GMA in patients with UC and 5-ASA intolerance. We conducted a retrospective observational study to evaluate the effectiveness and safety of GMA in patients with UC and 5-ASA intolerance. Eighty-five patients with UC who underwent GMA were assessed, including 21 with 5-ASA intolerance and 64 with 5-ASA tolerance. This study compared the patient characteristics, treatment outcomes, concomitant drugs, and adverse events between the 2 groups. The remission rate was 28.6% (6/21) in the 5-ASA-intolerant group and 31.3% (20/64) in the 5-ASA-tolerant group, with no significant difference between the groups (P = .967). Both groups showed significant reductions in the dose of oral prednisolone and Lichtiger clinical activity index scores following the GMA. Our study suggests that GMA is equally effective and safe in 5-ASA-intolerant and 5-ASA-tolerant patients, offering an alternative treatment option in this challenging clinical scenario.

Yukari Okubo ¹, Ryuhei Okuyama ², Shinichi Imafuku ³, Yayoi Tada ⁴, Keiichi Yamanaka ⁵, Kazumitsu Sugiura ⁶, Yukie Yamaguchi ⁷, Masahito Yasuda ⁸, Wataru Sakamoto ⁹, Morihisa Saitoh ⁹, Akimichi Morita ¹⁰; Study Investigators

Dermatol Ther (Heidelb). . 2025 Jul;15(7):1883-1899. doi: 10.1007/s13555-025-01429-8. Epub 2025 May 19.

Introduction: Generalized pustular psoriasis (GPP) is a rare, severe, and chronic inflammatory skin disease characterized by widespread pustules that leads to unpredictable and potentially serious disease flares. Information regarding treatment status for GPP and treatment patterns for flares is important but limited as a result of the rarity of the condition. We conducted a 10-year, retrospective, longitudinal chart review of treatment patterns at GPP referral hospitals in Japan.

Methods: Eligible patients with GPP had at least 6 months of continuous observation data within 10 years after the date of protocol approval. Data were collected from patient records and annual patient reports. Patient characteristics and treatment details, including in relation to flare occurrence, were analyzed.

Results: The median age of patients (N = 205) was 53 years; 48.3% were female and most had mild or moderate GPP (66.8%). Patients commonly received nonbiologic systemic therapy (86.3%) and a similar proportion received biologics (79.5%); 95.1% received topical treatment and 22.4% received systemic adrenal corticosteroids. Use of nonbiologic systemic therapy decreased, and use of biologics increased, over the study period. During the observation period, the proportion of patients receiving biologic therapy increased after a flare (from 41.4% receiving biologics when flares occurred to 62.9% initiating a new biologic post flare).

Conclusion: In Japanese clinical practice, the evolution of treatment practices for GPP has seen an increased use of biologic therapies over time. Biologic use was common after flares; however, some flares occurred during biologic therapy, indicating a need for improved treatment options to maintain stable disease and prevent flares.

Miki Urushiyama ¹, Kunio Tarasawa ², Rintaro Moroi ¹, Hideya Iwaki ¹, Yusuke Hoshi ³, Hiroshi Nagai ¹, Yusuke Shimoyama ¹, Takeo Naito ¹, Fumihiko Kakuta ³, Hisashi Shiga ¹, Shin Hamada ¹, Yoichi Kakuta ¹, Kiyohide Fushimi ⁴, Yoshitaka Kinouchi ¹, Daiki Abukawa ³, Kenji Fujimori ², Atsushi Masamune ¹

JGH Open. . 2025 May 14;9(5):e70175. doi: 10.1002/jgh3.70175. eCollection 2025 May.

Aims: This study aimed to investigate the trends in pediatric inflammatory bowel diseases (IBD) management in Japan over the past decade.

Methods: We retrospectively analyzed data from Japan’s nationwide database from 2012 to 2022. Patients aged ≤ 15 years diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) were included. Trends in the use of biologics, capsule endoscopy, total parenteral nutrition (TPN), elemental diets, surgery, and granulocyte and monocyte apheresis (GMA) were examined using the Cochrane-Armitage and Jonckheere-Terpstra trend tests.

Results: Among the 8037 and 6153 pediatric UC and CD admissions, respectively, the use of biologics increased significantly (CD: from 46.0% to 53.6%; UC: from 15.0% to 33.0%, p < 0.0001). The use of capsule endoscopy in pediatric patients with CD increased markedly from 6.6% to 16.7% (p < 0.0001), whereas TPN use decreased from 8.4% to 3.0% (p < 0.0001). Surgery rates for patients with CD remained at approximately 5%, whereas those for patients with UC decreased (from 3.7% to 1.7%, p = 0.002). Elemental diets for pediatric patients with CD increased (from 54.4% to 66.2%, p < 0.0001). The use of GMA decreased significantly in patients with UC (from 12.1% to 2.7%, p < 0.0001).

Conclusion: The use of biologics and capsule endoscopy has increased in pediatric patients with IBD, whereas the use of more invasive treatments has decreased. These trends suggest a shift toward less invasive and more targeted therapeutic strategies in managing pediatric patients with IBD in Japan.

M Hupé , G Bouguen , A Buisson , C Landman , M Uzzan , S Nancey , C Guillaume , G Cyrielle , M Charkaoui , M Serrero , A Wampach , M Collins , R Altwegg , F Cholet , A Amiot

Journal of Crohn’s and Colitis, Volume 19, Issue Supplement_1, January 2025, Page i1338, https://doi.org/10.1093/ecco-jcc/jjae190.0858

Background: Granulocyte and monocyte adsorptive apheresis (GMA) with ADACOLUMN® (JIMRO Takasaki Japan) is an effective and safe therapeutic option for patients with mild to moderate inflammatory bowel disease (IBD) refractory to pharmacological therapy, especially ulcerative colitis (UC). The aim of this study was to report effectiveness of GMA in patients with IBD.

Methods: All consecutive active, non-operated UC patients and Crohn’s disease (CD) patients treated with GMA in 15 French tertiary-care centres from 2007 to september 2024 were assessed. Patients received 4 to 8 weekly sessions of GMA alone or in combination with previously failing advanced therapy. Patients were assessed for effectiveness at week 14 and at week 54 for those continuing GMA as maintenance therapy and at every visit for safety. Clinical remission, steroid-free clinical remission, clinical response, colectomy as well as safety were ascertained.

Results: One hundred and twenty-nine patients with IBD (75 males, median age: 40.9 IQR[29.3-58.1] years, 102 with UC, IBD duration: 7.0 [2.9-13.1] years) were included. One hundred patients (77.5%) were previously treated with immunosuppressants and 97 (72.2%) with at least one anti-TNF. In patients with UC, baseline median total Mayo score was 7 [6-12] and mean CRP level was 23.3 ± 86.0 mg/L. In patients with CD, baseline median Harvey-Bradshaw index was 9 [7.25-10.75] and mean CRP level was 21.9 ± 27.3 mg/L. In patients with UC, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 27.5% and 52.0%, respectively. In patients with CD, week 14 clinical remission, steroid-free clinical remission and response rates were 33.3%, 29.6% and 66.7%, respectively. At week 14, nine patients with UC and 3 patients with CD required emergent surgery. At week 14, adverse events were reported in 26 (20.2%) and were mainly related to flare of IBD in 16 (12.4%). Other adverse events which were never classified as serious included headache in 3, arthromyalgia in 3 and abdominal pain, diarrhea, grade-1 increase in liver enzymes and mild hypotension in one. At week 54, 48 patients were still treated with maintenance GMA therapy including 13 with CD and 35 with UC. At week 54, steroid-free clinical remission rates were 38.5% (5/13) in patients with CD and 60% (21/35) in patients with UC.

Conclusion: In this real world cohort of patients with refractory IBD, GMA induced steroid-free clinical remission in one third of patients with CD and UC at W14. In patients continuing GMA maintenance therapy, steroid-free clinical remission was observed in one third of patients with CD and two thirds of patients with UC. Safety profile was favourable mostly related to relapse of IBD.

F Kenta, S Kensuke, T Shun, W Ryosuke, N Yusuke, Y Ren, S Kentaro, S Itsuki, O Hisashi, M Takuto
Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Page i1807, doi.org=10.1093/ecco-jcc/jjad212.1126

Background
Granulocyte and Monocyte Adsorption Apheresis (GMA) is one of the valuable non-immunosuppressive therapies in the treatment of ulcerative colitis (UC). However, due to the limited number of facilities where GMA can be performed, there are few reports on the combined effects of GMA and prednisolone (PSL), the frequency of GMA implementation or predictive factors for the effectiveness. In this study, we examined the combined effect of GMA and PSL as a remission induction therapy, the frequency of GMA and predictive factors.

Methods
A retrospective observational study was conducted at Kushiro Rosai Hospital. We analyzed clinical data from UC patients who underwent GMA from February 2015 to May 2023.

Results
The study included 54 patients (30 males and 24 females), with a median age of 48 years and a median disease duration of 2 years. The median Lichtiger-CAI (L-CAI) was 8. There were 43 patients of pancolitis. There were 51 biologics-naïve patients and 3 biologics-experienced patients. Concomitant medications included 5-ASA agents in 21 patients, immunomodulators in 7 patients, and PSL in 31 patients. The median CRP was 1.19 mg/dl and the median albumin was 3.5 g/dl. Adverse events were observed in 3 patients (fatigue, dizziness, palpitations). The median number of GMA sessions was 10, with 33 patients undergoing twice weekly and 9 patients three times weekly. The clinical remission rate was 80% (43/54), and the clinical response rate was 89% (48/54), with a significant improvement in the median L-CAI from 8 to 3 before and after GMA (P<0.001). In the comparison between the PSL concomitant group and the non-PSL group, the clinical remission rate was 83.9% (26/31) in PSL group and 73.9% (17/23) in non-PSLgroup (P=0.369). The clinical response rate was significantly higher in the PSL group (87% (27/31)) than in non-PSL group (52.2% (12/23)) (P=0.004). There was no significant difference in the clinical remission/response rate between the group that underwent GMA twice a week (76.9% (30/39)/84.6% (33/39)) and three times a week (77.8% (7/9)/77.8% (7/9)). In univariate analysis, biologics-naïve was extracted as a contributing factor to clinical remission. The cumulative remission rate at 52 weeks was 72% overall. There was no significant difference in the cumulative remission rate between the PSL group (76.8%) and the non-PSL group (67.6%) (P=0.524). There was also no significant difference between the twice-weekly group (75%) and the three-times-weekly group (57.1%) (P=0.236). Conclusion GMA for UC was found to be useful and safely performed as a remission induction therapy. Concomitant use of PSL increased the clinical response rate. The frequency of GMA showed that three times per week was as effective as two times per week.

Iago Rodríguez-Lago 1, Fiorella Cañete 2, Elena Guerra-Del-Río 3, Claudia Herrera-deGuise 4, Eva Iglesias 5, Eduardo Leo 6, Yamile Zabana 7, Manuel Barreiro-de Acosta 8, Daniel Ginard 9, José Luis Cabriada 10
Gastroenterol Hepatol. 2024 Jan 23:S0210-5705(24)00022-0. doi: 10.1016/j.gastrohep.2024.01.004. Online ahead of print.
[Article in English, Spanish]

Objective: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC.

Patients and methods: Retrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results: Twelve patients were included (median 46 years [IQR, 37-58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5-7), and it decreased to a median of 2 (IQR, 0-3) and 0 (IQR, 0-3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them. Conclusion: The combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug

Ayumi Ito ¹, Shun Murasugi ¹, Maria Yonezawa ¹, Teppei Omori ¹, Shinichi Nakamura ¹, Katsutoshi Tokushige ¹

J Clin Apher. 2024 Feb;39(1):e22099. doi: 10.1002/jca.22099. Epub 2023 Nov 21.

Background and aims: Primary sclerosing cholangitis has a poor prognosis and can be accompanied by ulcerative colitis. Infection control is essential, so immunosuppressive drugs should ideally be preferably. Granulocyte and monocyte adsorptive apheresis does not suppress the immune system and is used to treat ulcerative colitis. Therefore, this study investigated the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis and ulcerative colitis.

Methods: We retrospectively evaluated data from patients with primary sclerosing cholangitis with ulcerative colitis who visited our hospital from April 2000 to December 2022 and underwent granulocyte and monocyte adsorptive apheresis (n = 10, number of treatment cycles = 15). Study endpoints were remission induction rate and safety, assessed as changes in liver functions and adverse events. Results: Seven of the 10 patients were male. The median (min-max) age was 23 (18-77) years. The most common disease type was right-dominant pancolitis. Remission occurred after 86.6% of cycles (13/15). Serum alkaline phosphatase and Aspartate transaminase were significantly lower after treatment (P = .0124, P = .002), and no negative effects on liver function were seen. The only adverse events were headache (n = 1) and decreased blood pressure (n = 1).Conclusions: Granulocyte and monocyte adsorptive apheresis has high efficacy for intestinal lesions and improves alkaline phosphatase and aspartate transaminase levels (high levels are a poor prognosis factor). It appears to be a treatment option in patients with primary sclerosing cholangitis associated with ulcerative colitis.

I. Rodríguez-Lago1, F. Cañete2, E. Guerra3, C. Herrera de Guise4, E. Iglesias-Flores5, E. Leo-Carnerero6, Y. Zabana7, M. Barreiro de Acosta8, D. Ginard Vicens9, J.L. Cabriada Nuño1

UEG journal 2023 SUPPLEMENT ABSTRACT UEG Week 2023 Poster Presentations 15 October 2023 page 1067

Introduction: Granulocyte–monocyte apheresis (GMA) selectively removes activated leukocytes and immune mediators, and it has shown to be safe and effective in treating ulcerative colitis (UC). Previous reports
have also described its combination with biologics.
Aims & Methods: The aim of our study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. A retrospective, multicentre study was performed in 7 IBD Units, including all patients with refractory UC who received combined plus GMA and TOFA. The number of GMA sessions, its frequency, filtered blood volume and length of each
session were compiled, along with the clinical data. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, CRP and faecal calprotectin. Data regarding TOFA intensification, need for new immunomodulators/biologics and colectomy were also compiled. Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results: Twelve patients with UC were included (median 46 years [IQR, 37-58]; 67% female; 67% E3; 75% non-smokers). Patients were receiving TOFA10 mg bid (75%), 5 mg bid (16%), or 15 mg bid (8%), with 33% receiving
steroids at baseline. All patients had prior exposure to anti-TNF agents, 42% to vedolizumab and 8% ustekinumab. Median baseline Mayo score was 7 (IQR, 5-7), median CRP of 11 mg/L (IQR, 5-32) and faecal calprotectin 800 mg/kg (IQ, 715-2,094). GMA was started mostly after PNR (73%), and the median number of GMA sessions was 11 (IQR, 3-20) and 50% received maintenance GMA. Partial Mayo score significantly decreased 1 month after the last GMA session (p=0.027). Four patients (36%) were switched to a new therapy and no patient required colectomy during follow-up. All patients under steroids at baseline were able to stop them. No patient reported adverse events related to the combination therapy.

Conclusion: Combination of GMA with TOFA can be an effective and safe therapy in selected cases of UC after PNR or LOR to this drug.

Elena Céspedes Martínez, Virginia Robles Alonso, Claudia Herrera-De Guise, Luis Mayorga, Francesc Casellas, María Roca-Herrera, Natalia Borruel, Rev Esp Enferm Dig 2023;115(10):567-573

Introduction: immune checkpoint inhibitors (ICI) are increasingly used to treat several types of cancer. These drugs lead to a wide range of toxicities. Immune-related gastrointestinal adverse events are common and potentially severe. In this manuscript, we recount the real clinical experience in a tertiary center. Methods: a retrospective and observational study was conducted in adult patients under ICI treatment. Included patients had been referred to the Gastrointestinal Service of Hospital Universitario Vall d’Hebron for evaluation of severe toxicities, from January 2017 to January 2020, for whom the clinical, epidemiological and evolutive data were collected. Results: a total of 18 patients were included. Fifty-five percent received anti-programmed cell death protein 1 (PD-1)/anti-programmed death-ligand 1 (anti PD-L1), 11 % received anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and 33 % received both treatments. The toxicities were manifested as enterocolitis, microscopic colitis and gastritis. Upper gastrointestinal endoscopy was performed in seven patients; all were proved to have histological changes on duodenum biopsies. Treatment was stopped in all patients and steroids were initiated. Sixty-six per cent achieved clinical remission with steroids. Five patients received anti-TNF treatment (infliximab). Only one of the five had responded. Two anti-TNF refractory patients received ustekinumab, with an appropriate clinical response. One patient received apheresis granulocyte as concomitant treatment. A patient with a steroid-dependent course started vedolizumab. Three patients had other immune-related adverse events. Conclusion: gastrointestinal immune-related adverse events are acquiring a higher profile in daily practice and gastroenterologists play an even greater role in the management of these patients.

Severe and refractory gastrointestinal toxicity due to immune checkpoint inhibitors: clinical experience in a tertiary referral hospital – PubMed (nih.gov)

REED – Revista Española de Enfermedades Digestivas

Satoshi Tanida ^1 2, Keiji Ozeki ³, Takahito Katano ³, Mamoru Tanaka ³, Takaya Shimura ³, Eiji Kubota ³, Hiromi Kataoka ³, Takuya Takahama ², Shun Sasoh ², Yoshimasa Kubota ², Tesshin Ban ², Tomoaki Ando ², Makoto Nakamura ², Takashi Joh ²J Clin Med Res. 2023 Mar;15(3):181-186. doi: 10.14740/jocmr4887

Every-week (ew) adalimumab (ADA) maintenance following induction therapy with a standard induction regimen has recently been approved for use in Japan. The efficacy and safety of combination therapy with ew-ADA maintenance following standard induction regimen plus intensive granulocyte and monocyte adsorptive apheresis (GMA) (two sessions/week) for the treatment of refractory ulcerative colitis (UC) displaying failure of conventional, biologics and Janus kinase inhibitor have not been evaluated previously. The present retrospective study evaluated the 10-week efficacy of this combination therapy among refractory UC patients. Six patients were given initial ADA combination therapy (ADA at 160 mg in week 0, ADA 80 mg in week 2, and 40 mg in week 4, followed by ew-ADA at 40 mg/week) plus intensive GMA. One patient (16.6%) achieved clinical remission and two patients (33.3%) achieved endoscopic improvement by week 10. After excluding two patients who discontinued treatment, mean full Mayo score (P = 0.14), endoscopic subscore (P = 0.18) and C-reactive protein level (P = 0.27) at 10 weeks were numerically decreased compared with baseline in the remaining four cases, although the differences were not significant. Use of ew-ADA maintenance following standard induction regimen plus intensive GMA appears unlikely to achieve satisfactory induction of clinical remission in UC patients for whom conventional agents, biologics and Janus kinase inhibitors have failed.

Induction Therapy With a Combination of Weekly Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Ulcerative Colitis and Failure of Conventional Agents, Biologics and Janus Kinase Inhibitor – PubMed (nih.gov)

Induction Therapy With a Combination of Weekly Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Ulcerative Colitis and Failure of Conventional Agents, Biologics and Janus Kinase Inhibitor – PMC (nih.gov)