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.

Cristina Suárez Ferrer 1, Eduardo Martin-Arranz 2, María Dolores Martín-Arranz, Gastroenterol Hepatol 2024 Jan 12:S0210-5705(24)00018-9. doi: 10.1016/j.gastrohep.2024.01.002. Online ahead of print.
Aim: Granulocyte and monocyte apheresis (GMA) is a potential therapeutic option when combined with various drugs for treatment of ulcerative colitis (UC). In this study, we analyze the efficacy and safety of GMA combined with vedolizumab (VDZ) during induction in patients with moderate-severe UC and incomplete response to steroids.

Patients and methods: Single-center retrospective review of patients receiving GMA+VDZ. Data on the disease and previous treatments were collected. Clinical response was classified as no response, response without remission, and remission. Available data on biochemical and endoscopic response were included. Adverse events (AEs) were recorded.

Results: The study population comprised 6 patients with UC who had received GMA+VDZ during induction after failure of an anti-TNF agent. The median number of GMA sessions was 5 (IQR 4-5; 3-10). All the patients received VDZ 300mg iv at 0, 2, and 6 weeks, and 5 (83%) received an additional dose at week 10. During maintenance, all the patients continued VDZ iv every 8 weeks. The median follow-up was 57.6 months (IQR: 39-74). Four of the 6 patients achieved clinical remission after GMA+VDZ and continued in deep remission until the end of follow-up. A median, non-significant decrease of 1378μg/g (IQR: 924-5778μg/g) was observed for calprotectin and 42.2mg/l (IQR: 15.3-113.5) for CRP vs. baseline. No patient underwent colectomy. No treatment-related AEs were observed.

Conclusions: GMA+VDZ during induction can be effective and safe in selected patients with moderate-severe UC and partial response to steroids.

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)

Takumi Fukuchi , Kousaku Kawashima , Hideaki Koga , Ran Utsunomiya, Kohei Sugiyama , Keiji Shimazu , Takaaki Eguchi , Shunji Ishihara J Clin Biochem Nutr. 2022 Mar;70(2):197-204. doi: 10.3164/jcbn.21-112. Epub 2021 Dec 25.

This study examined the long-term maintenance rate after inducing remission by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids (CS) and GMA re-treatment efficacy in the same patients upon relapse with ulcerative colitis. Patients who achieved clinical remission and mucosal healing (MH) by first-time intensive GMA (first GMA) without CS were enrolled. The cumulative non-relapse survival rate up to week 156 was calculated. Patients with relapse during the maintenance period underwent second-time intensive GMA (second GMA) without CS. Clinical remission and MH rates following second GMA were compared to those following first GMA in the same patients. Of the 84 patients enrolled, 78 were followed until week 156 and 34 demonstrated relapse. The cumulative non-relapse survival rate by week 156 was 56.4%. Clinical remission and MH rates after second GMA did not differ from those after first GMA in the same patients (week 6: clinical remission, 100% vs 88.4%, p = 0.134; MH, 100% vs 84.8%, p = 0.074). In conclusion, MH induction by intensive GMA without use of CS in ulcerative colitis patients contributes to subsequent long-term clinical remission maintenance. GMA re-treatment efficacy was comparable to that of first GMA in the same patients who had relapse.

https://pubmed.ncbi.nlm.nih.gov/35400813/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921725/

Masanao Nakamura ¹, Takeshi Yamamura ¹, Keiko Maeda ², Tsunaki Sawada ², Yasuyuki Mizutani ¹, Eri Ishikawa ¹, Ayako Ohashi ¹, Go Kajikawa ¹, Kazuhiro Furukawa ¹, Eizaburo Ohno ¹, Takashi Honda ¹, Hiroki Kawashima ¹, Masatoshi Ishigami ¹, Mitsuhiro Fujishiro ¹

Intern Med. 2020 Dec 1;59(23):3009-3014. doi: 10.2169/internalmedicine.5302-20. Epub 2020 Jul 28.

Granulocyte and monocyte adsorptive apheresis (GMA) is occasionally introduced as an alternative combination therapy after loss of response to biologics in ulcerative colitis (UC) patients. However, there have been no reports of the concomitant use of vedolizumab (VDZ) and GMA for the initial induction of UC. A 20-year-old man with refractory UC was admitted for recrudescence. VDZ monotherapy had previously been introduced but was ineffective. Therefore, he received scheduled combination of VDZ and GMA and achieved clinical remission. The combination of two different approaches to inhibit the migration of leukocytes into the inflamed tissue led to satisfactory clinical outcomes.

https://pubmed.ncbi.nlm.nih.gov/32727993/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759717/

Satoshi Tanida ¹, Keiji Ozeki ¹, Tsutomu Mizoshita ¹, Mika Kitagawa ¹, Takanori Ozeki ¹, Mamoru Tanaka ¹, Hirotada Nishie ¹, Takaya Shimura ¹, Eiji Kubota ¹, Hiromi Kataoka ¹ , J Clin Med Res, 2020 Jan;12(1):36-40.

Based on these outcomes, combination therapy with TOF plus intensive GMA was well tolerated and may be useful for induction of clinical remission in patients with refractory UC.

https://pubmed.ncbi.nlm.nih.gov/32010420/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968921/pdf/jocmr-12-036.pdf

Kazuaki Inoue, Tomoki Furuya, Yoko Yokoyama

The apheresis guidelines for digestive diseases are divided into the following four fields: acute liver failure (ALF); ascites; acute pancreatitis (AP); inflammatory bowel disease (IBD).

IBD: Ulcerative colitis (UC) and Crohn’s disease (CD) are the major forms of I BD. Although their etiology is still not fully understood, activated leukocytes are significant factors in their exacerbations. In Japan, granulocyte and monocyte apheresis (GMA) and leukocytapheresis (LCAP) are approved for IBD treatment. They are recommended for remission induction in UC
patients with mild-to-moderate activity, whether steroid-resistant or -dependent. Although GMA is recommended for remission induction in colonic type CD refractory to conventional therapy, its efficacy is lower than in UC patients.

poster at ISFA 2019 pag 100-101

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

Satoko Yamasaki ¹, Yasuhisa Sakata ², Hisako Yoshida ³, Sinpei Shirai ¹, Yuichiro Tanaka ¹, Ryo Nakano ¹, Takahiro Yukimoto ¹, Nanae Tsuruoka ¹, Ryo Shimoda ¹, Makoto Fukuda ¹, Motoaki Miyazono ¹, Yuji Ikeda ¹, Ryuichi Iwakiri ¹, Keizo Anzai ¹, Kazuma Fujimoto ¹ , Digestion. 2019;100(4):247-253.

Background: Leukocyte removal therapy (LRT) is an effective treatment for active ulcerative colitis (UC). The present study was performed to evaluate the relapse-free period after LRT and identify risk factors for relapse. Methods: In total, 94 patients who underwent first-time LRT for remission of moderate to severe UC from April 2004 to March 2016 were enrolled in the present study. The patients were randomly assigned to one of 2 treatments: leukocytapheresis (LCAP; n = 43) or granulocyte and monocyte/macrophage adsorptive apheresis (GMA; n = 51). The 5-year cumulative relapse-free rate and risk factors for relapse were evaluated. Results: The therapeutic response rate was 82% for GMA and 70% for LCAP without a statistically significant difference. The 5-year relapse-free rate was 34.7% in the LRT group. The 5-year relapse-free rate in patients aged > 40 years was 49.9%, which was significantly higher than that in patients aged ≤40 years (22.9%, p < 0.01). The relapse-free period was longer in the older than younger patients. The relapse-free period was longer in the ≥40- than <40-year-old patients (1,197 vs. 441 days, respectively; p = 0.03). Conclusions: The relapse-free period after LRT was examined in patients with UC, and 34.7% of patients achieved clinical remission within a 5-year period. The risk factor for early relapse after LRT was younger age. In conclusion, LRT might be a therapeutic option for maintenance of remission in patients with UC, especially patients aged ≥40 years.

https://pubmed.ncbi.nlm.nih.gov/30540999/