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.

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.

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

Hepatol Commun. 2024 Jan 29;8(2):e0371. doi: 10.1097/HC9.0000000000000371. eCollection 2024 Feb 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).