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)

Makoto Naganuma ¹, Taku Kobayashi ², Reiko Kunisaki ³, Katsuyoshi Matsuoka ⁴, Shojiro Yamamoto ⁵, Ami Kawamoto ⁶, Daisuke Saito ⁷, Kosaku Nanki ⁸, Kazuyuki Narimatsu ⁹, Hisashi Shiga ¹⁰, Motohiro Esaki ¹¹, Shinichiro Yoshioka ¹², Shingo Kato ¹³, Masayuki Saruta ¹⁴, Shinji Tanaka ¹⁵, Eriko Yasutomi ¹⁶, Kaoru Yokoyama ¹⁷, Kei Moriya ¹⁸, Yoshikazu Tsuzuki ¹⁹, Makoto Ooi ²⁰, Mikihiro Fujiya ²¹, Atsushi Nakazawa ²², Takayuki Abe ²³, Tadakazu Hisamatsu ⁶; Japanese UC Study Group J Gastroenterol. 2023 Dec;58(12):1198-1210. doi: 10.1007/s00535-023-02048-w. 

Background: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC).

Methods: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT.

Results: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization.

Conclusion: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.

Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis – PubMed (nih.gov)

Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis | Journal of Gastroenterology (springer.com)

Kazunori Adachi ¹, Tomoya Sugiyama ², Yoshiharu Yamaguchi ², Yasuhiro Tamura ², Shinya Izawa ², Masahide Ebi ², Yasushi Funaki ², Naotaka Ogasawara ², Makoto Sasaki ², Kunio Kasugai ² Clin J Gastroenterol. 2023 Feb;16(1):43-47.

A 46-year-old man, receiving continuous steroid therapy for refractory ulcerative colitis with an insufficient response to anti-tumor necrosis factor-α therapy, presented with left buttock pain. He was diagnosed with steroidal left femoral head necrosis, and total proctocolectomy with permanent ileostomy was performed. At 6 months postoperatively, the patient developed general fatigue, abdominal pain, and severe ileostomy diarrhea. Computed tomography revealed continuous intestinal edema from the descending duodenal leg to the upper jejunum. Gastrointestinal endoscopy revealed deep ulcers, coarse mucosa, and duodenal erosion. Based on clinical progress, findings, and pathology, the patient was diagnosed with ulcerative colitis-related postoperative enteritis. Although 5-aminosalicylic acid treatment was initiated, his symptoms persisted, bloody diarrhea from colostomy was observed. Subsequently, granulocyte and monocyte apheresis treatment was added. Symptoms and endoscopic findings improved with granulocyte and monocyte apheresis. Azathioprine was introduced as maintenance therapy, and no sign of recurrence was observed. Although ulcerative colitis-related postoperative enteritis has no definitive treatment, granulocyte and monocyte apheresis may be considered for initial treatment.

A case of ulcerative colitis-related postoperative enteritis treated with granulocyte and monocyte apheresis – PubMed (nih.gov)

A case of ulcerative colitis-related postoperative enteritis treated with granulocyte and monocyte apheresis | Clinical Journal of Gastroenterology (springer.com)

Farah Yasmin ¹, Hala Najeeb ¹, Unaiza Naeem ¹, Abdul Moeed ¹, Thoyaja Koritala ², Salim Surani ^3 4World J Clin Cases. 2022 Jul 26;10(21):7195-7208.

Inflammatory Bowel Disease (IBD) is a hallmark of leukocyte infiltration, followed by the release of cytokines and interleukins. Disease progression to Ulcerative Colitis (UC) or Crohn’s Disease (CD) remained largely incurable. The genetic and environmental factors disrupt enteral bacteria in the gut, which hampers the intestinal repairing capability of damaged mucosa. Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor (TNF)-α. New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response. This review discusses the non-pharmacologic selective granulocyte-monocyte-apheresis (GMA) and leukocytapheresis (LCAP) that have been proposed as treatment modalities that reduce mortality. GMA, an extracorporeal vein-to-vein technique, presents a strong safety profile case for its use as a viable therapeutic option compared to GMA’s conventional medication safety profile. GMA reported minimal to no side effects in the pediatric population and pregnant women. Numerous studies report the efficacious nature of GMA in UC patients, whereas data on CD patients is insufficient. Its benefits outweigh the risks and are emerging as a favored non-pharmacological treatment option. On the contrary, LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release. It has been deemed more efficacious than conventional drug treatments, the former causing better disease remission, and maintenance. Patients with UC/CD secondary to complications have responded well to the treatment. Side effects of the procedure have remained mild to moderate, and there is little evidence of any severe adverse event occurring in most age groups. LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD. The review will discuss the role of GMA and LCAP.

Apheresis: A cell-based therapeutic tool for the inflammatory bowel disease – PubMed (nih.gov)

Apheresis: A cell-based therapeutic tool for the inflammatory bowel disease – PMC (nih.gov)

Zhaobei Cai ^1 2, Shu Wang ³, Jiannan Li ¹ Front Med (Lausanne)  2021 Dec 20;8:765474. doi: 10.3389/fmed.2021.765474. eCollection 2021.

Inflammatory bowel disease (IBD), as a global disease, has attracted much research interest. Constant research has led to a better understanding of the disease condition and further promoted its management. We here reviewed the conventional and the novel drugs and therapies, as well as the potential ones, which have shown promise in preclinical studies and are likely to be effective future therapies. The conventional treatments aim at controlling symptoms through pharmacotherapy, including aminosalicylates, corticosteroids, immunomodulators, and biologics, with other general measures and/or surgical resection if necessary. However, a considerable fraction of patients do not respond to available treatments or lose response, which calls for new therapeutic strategies. Diverse therapeutic options are emerging, involving small molecules, apheresis therapy, improved intestinal microecology, cell therapy, and exosome therapy. In addition, patient education partly upgrades the efficacy of IBD treatment. Recent advances in the management of IBD have led to a paradigm shift in the treatment goals, from targeting symptom-free daily life to shooting for mucosal healing. In this review, the latest progress in IBD treatment is summarized to understand the advantages, pitfalls, and research prospects of different drugs and therapies and to provide a basis for the clinical decision and further research of IBD.

https://pubmed.ncbi.nlm.nih.gov/34988090/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720971/

Asumi Fujii, Yuki Hattori, Miho Kawamura, Yoko Mizutani, En Shu, Mariko Seishima

poster at ISFA 2019 pag 141-142

A 31-year-old woman with the IL36RN gene mutation developed psoriasis at 3 years old. As she had pustular psoriasis at 16 years old, she was treated with cyclosporine (Cys), resulting in remission at 20 years old. Afterwards, she had been maintained by topical treatment for long years.During the first pregnancy at the age of 29, she developed pustular psoriasis at 29 weeks
of gestation. She received one course of granulocyte / monocyte adsorption apheresis (GMA) with Cys and prednisolone (PSL), and gave birth to a girl at 33 weeks of gestation. The baby was a low birth weight child, but is healthy and has no problems in growth and development until now. However, the patient did not sufficiently improve symptoms after delivery. We thus started the treatment with infliximab (IFX) BS at 2 months postpartum. During the second pregnancy at the age of 30, we continued the IFX-BS administration. She had erythema and pustules rapidly enlarged from 23 weeks of pregnancy. Oral administration of PSL and GMA were started. However, we switched the therapy to intensive GMA (twice in a week), because the effect was insufficient. Initially, administration of IFX-BS was scheduled to end at 30 weeks of gestation, but due to unstable symptoms, we considered it was necessary to use another biologics even after 30 weeks of gestation. We switched to non-placental certolizumab pegol (CTZ) from 26 weeks of gestation and continued the administration until delivery, and she gave birth to a girl at 35 weeks of gestation. Although the baby was a low birth weight child, there was no physical abnormality and the baby was discharged after gaining weight. After delivery, administration of CTZ was discontinued and the PSL dose was gradually reduced. However,reintroduction of biologics is under consideration, because erythema and pustules still remain.

http://www.atalacia.com/isfa/data/abstract.pdf