E Papathanasiou , P Markopoulos , M Tzouvala , A Ioannou , E Tsironi , E Zacharopoulou , M Tzakri , E Pantelakis , G Leonidakis , G Bamias , S Michopoulos , E Zampeli

Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Pages i1356–i1357, https://doi.org/10.1093/ecco-jcc/jjad212.0857

Background: Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with Adacolumn ^® was introduced as a nonpharmacologic treatment for ulcerative colitis (UC) in 2000. It has been reported that GMA may be effective in combination with immunosuppressive treatment in a subset of patients. Τhe purpose of our study is the evaluation of the effectiveness and safety of GMA as a complementary treatment in patients with refractory ulcerative colitis.

Methods: Prospective data collection of a patient cohort with refractory UC receiving Adacolumn ^® as an adjunct to their medical treatment. The therapeutic protocol has 2 phases: The induction phase entails two sessions per week for at least 3 weeks. The maintenance includes one weekly session for one month, one session every 15 days for one the next month, and monthly sessions thereafter. The patients’ medical treatment was maintained during the sessions. As a failure to GMA was considered the need for colectomy, the switch to a different treatment and inability to discontinue steroids. Response was evaluated after completion of at least 6 sessions of GMA.

Results: Ten patients with refractory UC were offered Adacolumn^® between February 2021 and September 2023. Mean age was 39.6 years (22-61years). All patients had failed at least one biologic treatment and two-thirds two biologics. Their treatment which was maintained during GMA was: tofacitinib 10mg bid for 4 patients, ustekinumab 90mg sc every 8 weeks for 3, vedolizumab 300 mg every 8 weeks for 2, and corticosteroids 16mg for one. The median duration of treatment was 5.1 months (2-13 months), while the median number of sessions was 16 (6-45). Clinical and endoscopic remission was achieved in two cases (20%), after 13 sessions for both (in brackets in the Table) whereas two patients (20%) responded clinically according to partial Mayo score. Treatment failure was documented for 6 patients (60%) after 6-45 sessions. Patient number 4 performed 45 sessions in different hospitals because he was reluctant to be operated. Three underwent colectomy and three discontinued due to non-response. No adverse effects were observed. The initial median of partial Mayo score was 6 (5-9) while at the end of the evaluation was 4.5 (0-9). Table 1 summarizes the results of our study.

Conclusion

1) GMA may be beneficial as an adjunct to biologics in refractory to medical treatment UC patients.

2) Interestingly, all patients on tofacitinib showed a favorable response after the addition of GMA.

This observation may help define a subset of UC patients who may benefit the most.

Jiménez-Cortegana Carlos , Palomares Francisca , Alba Gonzalo, Santa-María Consuelo , de la Cruz-Merino Luis , Sánchez-Margalet Victor , López-Enríquez Soledad Frontiers in Immunology 14,2024, doi.org=10.3389/fimmu.2023.1321051

Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD). In line with those notions, different therapeutic approaches have been tested to enhance or impair the concentration and role of the different DC subsets. The blockade of inhibitory pathways to promote DCs or DC-based vaccines have been successfully assessed in cancer, whereas the targeting of DCs to inhibit their functionality has proved to be favorable in IBD. In this review, we (a) described the general role of DCs, (b) explained the DC subsets and their role in immunogenicity, (c) analyzed the role of DCs in cancer and therapeutic approaches to promote immunogenic DCs and (d) analyzed the role of DCs in IBD and therapeutic approaches to reduced DC-induced inflammation. Therefore, we aimed to highlight the “yin-yang” role of DCs to improve the understand of this type of cells in disease progression.

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

Hikaru Ishihara ¹, Tatsuyuki Watanabe ², Shinsuke Kumei ², Keiichiro Kume ², Ichiro Yoshikawa ², Masaru Harada ² Clin J Gastroenterol. 2023 Dec 2. doi: 10.1007/s12328-023-01887-7.

A 68-year-old man developed immune-related adverse event (irAE) colitis after the initiation of nivolumab and ipilimumab combination therapy for malignant melanoma. We diagnosed the patient with grade 3 irAE colitis and started prednisolone (1 mg/kg/day). Although the symptom improved once, it worsened along with the tapering of prednisolone. Therefore, we started infliximab (IFX). However, symptoms did not improve after two doses of IFX. We discontinued IFX and initiated vedolizumab (VED). Because VED alone did not improve the symptom, we started granulocyte-monocyte apheresis (GMA). Twelve weeks after the onset, the colitis was in remission. Therefore, in addition to vedolizumab, GMA may be considered in cases refractory to treatment.

A case of refractory immune checkpoint inhibitor-induced colitis improved by the treatment with vedolizumab and granulocyte-monocyte apheresis combination therapy – PubMed (nih.gov)

A case of refractory immune checkpoint inhibitor-induced colitis improved by the treatment with vedolizumab and granulocyte–monocyte apheresis combination therapy | Clinical Journal of Gastroenterology (springer.com)

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.

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

J Clin Apher. 2023 Nov 21. doi: 10.1002/jca.22099.

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.

A retrospective study to investigate the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis with ulcerative colitis – PubMed (nih.gov)

A retrospective study to investigate the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis with ulcerative colitis – Ito – Journal of Clinical Apheresis – Wiley Online Library

Shun Murasugi, Maria Yonezawa, Teppei Omori, Shinichi Nakamura, Katsutoshi Tokushige . J Clin Apher. 2024; 39(1):e22099. doi:10.1002/jca.22099

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.

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.