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.

Hideaki Uchida ¹, Masahiro Kamata ², Shota Egawa ¹, Mayumi Nagata ¹, Saki Fukaya ¹, Kotaro Hayashi ¹, Atsuko Fukuyasu ¹, Takamitsu Tanaka ¹, Takeko Ishikawa ¹, Takamitsu Ohnishi ¹, Kazumitsu Sugiura ³, Yayoi Tada 

J Am Acad Dermatol 2022 Nov;87(5):1181-1184. doi: 10.1016/j.jaad.2022.03.001. 

Granulocyte and monocyte adsorption apheresis (GMA) is an extracorporeal circulation therapy that removes activated granulocytes and monocytes, which can be easily introduced in clinics and hospitals where hemodialysis is performed. Its safety profile  allows for its administration without screening and for its concomitant use with other therapies, indicating that GMA can be a good additional option for GPP treatment. However, the evidence for its efficacy and safety is limited because of the rarity of GPP. Furthermore, its immediate impact on GPP has not been assessed yet. Therefore, we report our real-world experience of 14 patients with GPP treated with GMA after systemic treatment.GMA can be administered with other systemic therapies, including biologics and conventional therapy (objective A). Furthermore, its good safety profile allows GMA administration to a wide range of patients, including elderly patients and those with complications, possible active infection, or malignancy (objectives B and C). Moreover, our study revealed an immediate significant improvement in BT, accompanied by slight decreases in the WBC count and CRP level, indicating that GMA contributes to the rapid suppression of acute inflammation in patients with GPP.

A real-world, single-center experience and the immediate impact of granulocyte and monocyte adsorption apheresis on generalized pustular psoriasis – PubMed (nih.gov)

A real-world, single-center experience and the immediate impact of granulocyte and monocyte adsorption apheresis on generalized pustular psoriasis – Journal of the American Academy of Dermatology (jaad.org)

Keiji Matsuda ^1 2, Kohei Ohno ¹, Yuka Okada ¹, Takahiro Yagi ¹, Mitsuo Tsukamoto ¹, Yoshihisa Fukushima ¹, Atsushi Horiuchi ¹, Ryu Shimada ^1 2, Tsuyoshi Ozawa ^1 2, Tamuro Hayama ^1 2, Takeshi Tsuchiya ^1 2, Junko Tamura ¹, Hisae Iinuma ¹, Keijiro Nozawa ^1 2, Hitoshi Aoyagi ^2 3, Akari Isono ^2 3, Koichiro Abe ^2 3, Shinya Kodashima ^2 3, Takatsugu Yamamoto ^2 3, Yoshitaka Kawasaki ⁴, Yoshifuru Tamura ⁴, Yuko Sasajima ⁵, Fukuo Kondo ⁵, Yojiro Hashiguchi ^1 2 , Inflamm Intest Dis, 2020 Feb;5(1):36-41.

The effect of GMA with concomitant PSL (Prednisolone) and that of GMA without PSL were not different, and GMA was effective irrespective of PSL administration. The present study showed that GMA had efficacy and led many UC patients treated by PSL to be steroid free with no safety concern in the real world, although there is the possibility of recruitment bias due to the retrospective nature of the study.

https://pubmed.ncbi.nlm.nih.gov/32232053/

https://www.karger.com/Article/Pdf/505484

Taku Kobayashi

poster at ISFA 2019 pag 53

There are two types of extracorporeal therapy for treating active ulcerative colitis (UC), granulocyte and monocyte adsorption (GMA) and leukocytapheresis (LCAP). Although Sawada et al reported the efficacy of LCAP by the randomized controlled trial (Sawada K et al. Am J Gastroenterol 2005), the larger sham-controlled multicenter trial of GMA failed to prove its efficacy (Sands BE et al. Gastroenterol 2008). Therefore, evidence to show their efficacy relies more on the real-world data, including the post-marketing surveillance (PMS). The large-scale PMS for LCAP was named as REFINE study, involving 847 patients from 116 medical facilities in Japan (Yokoyama Y, Kobayashi T et al. J Crohn Colitis 2014). Adverse events were seen only in 10.3% and the vast majority were mild. The overall clinical remission rate was 68.9%, and the mucosal healing rate was 62.5%. These results were very consistent with the results from PMS of 697 patients treated with GMA, which also demonstrated its real-world effectiveness and safety (Hibi T et al. Dig Liver Dis 2008). In addition, a retrospective observational study aimed to evaluate the clinical outcome at 1 year and identify risk factors for relapse after LCAP was recently conducted among patients who had achieved remission in the PMS (Kobayashi T et al. J Gastroenterol 2018). The 1-year cumulative relapse free rate was 63.6%. Following LCAP, a high clinical activity and a high leukocyte count were associated with a greater risk of relapse. Intensive LCAP was associated with favorable long-term outcomes in corticosteroidrefractory patients. The response rate of re-treatment upon relapse was as high as 85%. These results on the risks of relapse as well as effectiveness of re-treatment may help to overcome the weakness of cytapheresis therapy in maintaining remission. Results from the clinical trial evaluating the clinical efficacy of intermittent maintenance cytapheresis therapy are also warranted.

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