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.

Tomotaka Tanaka ¹, Daiki Hirano ¹, Syohei Ishimaru ¹, Keiko Arataki ¹

Cureus 2025 Jan 18;17(1):e77641. doi: 10.7759/cureus.77641. eCollection 2025 Jan.

We report the case of a 37-year-old male patient diagnosed with moderate left-sided ulcerative colitis (UC). Initial therapy with 5-aminosalicylic acid (5-ASA) was terminated within days due to exacerbation of symptoms, leading to a diagnosis of 5-ASA intolerance. Although induction of remission was achieved with prednisolone, the patient developed steroid dependency. Treatment with vedolizumab and ustekinumab subsequently failed to achieve clinical or endoscopic improvement. Intensive granulocyte and monocyte apheresis (GMA) was introduced, successfully inducing remission. However, during maintenance therapy with GMA, the patient experienced a relapse. Initiation of golimumab yielded suboptimal results, necessitating a combination therapy involving prednisolone and reintensified intensive GMA. This multimodal approach successfully achieved remission induction and maintenance. This case highlights the potential utility of intensive GMA in combination with golimumab and prednisolone for the management of refractory UC, particularly in patients with 5-ASA intolerance and failure of multiple biologic agents. A brief review of the relevant literature is included.

Maki Setake ¹, Ryosaku Tomiyama ¹, Tomoya Kuda ², Kanetaka Maeshiro ³, Akira Hokama ⁴

Rev Esp Enferm Dig. 2024 Oct 4. doi: 10.17235/reed.2024.10795/2024. 

A 17-year-old man with ulcerative colitis (UC) presented to our hospital with neck pain and fever after vomiting. On examination, a snowflake sensation was noted in the neck. A chest radiograph showed extensive subcutaneous emphysema in the chest. CT scans showed extensive subcutaneous emphysema in the neck, shoulders and axilla, as well as pneumomediastinum and pneumothorax. A diagnosis of pneumomediastinum with exacerbation of UC was made, and he was fasted and treated with antibiotics. Intensive granulocyte and monocyte adsorption apheresis (GMA) was started for exacerbation of UC. His symptoms and the radiological findings of pneumomediastinum improved. He remained in remission on azathioprine. UC is a chronic inflammatory bowel disease (IBD) associated with extraintestinal manifestations (EIM). Very few cases have been complicated by pneumomediastinum. The increase in alveolar pressure due to vomiting and systemic inflammation-related pleural or esophageal damage may cause pneumomediastinum in this case. Prevention of progression to mediastinitis and treatment of exacerbated UC are contradictory. GMA was successful because it was not an immunosuppressive therapy. Our case highlights that rare EIM may complicate exacerbation of UC.

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).

I Rodríguez-Lago, D Ginard, R J Díaz Molina, M Vicuña, E Domenech, M Abanades, O Moralejo Lozano, G Bastida, A D Sánchez Capilla, E Iglesias, F Rancel-Medina, M D M Blasco, M Bosca-Watts, M Calvo Iñiguez, C Herrera deGuisé, E Leo, A Viejo Almanzor, V Hernández Ramirez, C Suárez Ferrer, L Quilez Pérez, M Muñoz, F Fernández Pérez, J M Huguet, P Fradejas, C López Ramos, A M Fuentes Coronel, C Reygosa Castro, N Rull Murillo, P Zapico, J L Cabriada
Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Page i1011, doi.org=10.1093/ecco-jcc/jjad212.0641

Background
The clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn in patients (pts) with inflammatory bowel disease (IBD) has been reported in several clinical trials (CT), with significant clinical remission rates. However, evidence on real-world effectiveness of GMA with Adacolumn in ulcerative colitis (UC) or Crohn’s disease (CD) patients who were underrepresented in CT is still limited.

Methods
GRACE is a multicentric, prospective observational study conducted at 31 centres in Spain. The study included adults (≥18 years) diagnosed with UC or CD who had been scheduled to receive GMA with Adacolumn in clinical practice. The study consisted of a baseline (GMA initiation) and 3 follow-up visits at 4, 24, and 48 weeks after the last GMA session. The primary endpoint is the steroid-free remission rate at 24 weeks. This interim analysis is focused on clinical characterization of patients and their management and outcome 4 weeks after GMA treatment.

Results
A total of 95 evaluable patients were included at data cut-off date (25 Sept 2023) (median age: 54 years; 50% men: 81% outpatients). Overall, 89.4% (n=84) of patients had UC, being moderate-to-severe in 85.5%; 57,8% had pancolitis, and the median Mayo score was 5 (interquartile range [IQR], 3-6). Out of the 10 patients (10.6%) with CD, all had B1, and 3 patients had L1, 4 L2 and 3 L3. Overall, 17% had extraintestinal manifestations. Regarding IBD-related therapy, 52.6% of patients had previously received anti-TNF agents, 37.9% thiopurines, and 17.8% JAK inhibitors. Overall, 85.3% of patients received concomitant treatment with GMA, most commonly 5-ASA (60%), corticosteroids (51,6%), ustekinumab (20%), vedolizumab (17.9%), and anti-TNF therapy (11.6%). A total of 71 patients reached the 4-week visit after receiving a median of 10 (IQR, 8-10) GMA sessions (weekly: 26.3%, biweekly: 36.8%, and weekly/biweekly: 31.6%). At week 4, clinical remission was achieved by 50.7% of patients (UC: 49.2%; CD: 66.7%), being 50% and 53.3% in patients concomitantly treated with ustekinumab and vedolizumab. Steroid-free remission rate was 26.1% (UC: 22.2%; CD: 66.7%) at week 4. Overall, 11,2% of patients experienced AEs related to GMA, most of them being mild (73%) or moderate (22.4%). Most common AEs were headache and asthenia. No SAEs were observed.

Conclusion
Preliminary data at 4 weeks show that Adacolumn is a safe and effective treatment in a cohort of IBD refractory patients with previous failure to multiple therapies including thiopurines, biologics and JAK inhibitors. Half of patients were concomitantly treated with biologics, and their clinical remission rate was similar to the overall population. Long-term results of this study (48 weeks) are required to confirm these findings.

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.

Satoshi Tanida 1 2, Ryoji Kubo 3, Shoichiro Yoshii 3, Takuya Takahama 2, Shun Sasoh 2, Yoshimasa Kubota 2, Tesshin Ban 2, Tomoaki Ando 2, Makoto Nakamura 2, Takashi Joh 2 Case Reports J Clin Med Res . 2023 Dec;15(10-11):446-455. doi: 10.14740/jocmr5005. Epub 2023 Nov 3.

A 44-year-old woman who had been diagnosed with ulcerative colitis (UC) at 22 years old was diagnosed with severe flare-up of UC based on endoscopic findings associated with new-onset active pyoderma gangrenosum (PG) on both lower legs after she decided to discontinue UC treatment. Systemic treatment with intravenous prednisolone at 30 mg/day had achieved insufficient response to UC and PG, resulting in a diagnosis of corticosteroid-refractory UC and PG. Combination therapy with upadacitinib at 45 mg/day plus intensive granulocyte and monocyte adsorptive apheresis (GMA) was started to achieve clinical remission of UC. Ten weeks after starting this combination therapy, clinical improvement of UC was achieved with PG ulcer healing on both lower legs. A combination of upadacitinib plus intensive GMA may offer an effective therapeutic option for patients with active PG in addition to UC but has yet to be approved for induction or maintenance treatment of PG worldwide. PG is a dermatological involvement in UC patients that requires attention.

Esteban Sáez-González MD, Inés Moret-Tatay PhD, Guillermo Bastida MD, PhD, Mariam Aguas MD, PhD, Marisa Iborra MD, PhD, Pilar Nos MD, PhD, Belén Beltrán MD, PhD  J Clin Apher. 2023 38(6); 1-10. doi:10.1002/jca.22101

Background

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, affecting millions of individuals throughout the world, and producing an impaired health-related quality of life. Granulocyte and monocyte apheresis (GMA) is a therapeutic option for UC management to induce remission by selective removal of activated leukocytes from bloodstream. Despite the knowledge of the important role of epigenetics in UC pathogenesis, and in the response to different treatments, nothing is known about the role of microRNAs in GMA therapy in UC patients.

Methods

7 consecutively UC patients who started GMA in combo therapy with infliximab were recruited. Peripheral blood samples were taken before the apheresis session, at the start of the induction (S0) and at the end (S10). They were follow-up during the induction phase (10 sessions: 2 sessions for a week during 3 wk and 1 session for a week during 4 wk) of the treatment at a tertiary hospital (Hospital la Fe) and 6 mo after finishing the GMA induction therapy. MiRNA was extracted and analyzed by RT-PCR. R software and GraphPad were used.

Results

Clinical disease activity significantly decreased after induction therapy with GMA (median partial Mayo score 2 (IQR, 1-6) (P < .05). Fecal calprotectin value and CRP value significantly decreased after induction therapy. Five microRNAs modified their expression during GMA (unsupervised analysis): miR-342-3p, miR-215-5p, miR-376c-3p, miR-139-5p, and miR-150-5p. When a sub-analysis was performed in those patients who showed good response to apheresis treatment (n = 5), two microRNAs showed to be implicated: miR-215-5p and miR-365a-3p. These are preliminary but promising and novel results, as it is the first time, to our knowledge that microRNA profiles have been studied in the context of GMA treatment for IBD.

MicroRNA and granulocyte-monocyte adsorption apheresis combotherapy after inadequate response to anti-TNF agents in ulcerative colitis – PubMed (nih.gov)

MicroRNA and granulocyte‐monocyte adsorption apheresis combotherapy after inadequate response to anti‐TNF agents in ulcerative colitis – Sáez‐González – Journal of Clinical Apheresis – Wiley Online Library

Mauro Mastronardi, Elisabetta Cavalcanti, Nunzia Labarile, Raffaele Armentano, Francesco Gabriele, Margherita Curlo, Therapeutic Advances in Chronic Disease. 2023;14. doi:10.1177/20406223231194190

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn’s disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.

Mauro Mastronardi 1, Elisabetta Cavalcanti 2, Nunzia Labarile 1, Raffaele Armentano 3, Francesco Gabriele 4, Margherita Curlo 1 Ther Adv Chronic Dis. 2023 Nov 3:14:20406223231194190. doi: 10.1177/20406223231194190.

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn’s disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.