F Kenta, S Kensuke, T Shun, W Ryosuke, N Yusuke, Y Ren, S Kentaro, S Itsuki, O Hisashi, M Takuto
Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Page i1807, doi.org=10.1093/ecco-jcc/jjad212.1126

Background
Granulocyte and Monocyte Adsorption Apheresis (GMA) is one of the valuable non-immunosuppressive therapies in the treatment of ulcerative colitis (UC). However, due to the limited number of facilities where GMA can be performed, there are few reports on the combined effects of GMA and prednisolone (PSL), the frequency of GMA implementation or predictive factors for the effectiveness. In this study, we examined the combined effect of GMA and PSL as a remission induction therapy, the frequency of GMA and predictive factors.

Methods
A retrospective observational study was conducted at Kushiro Rosai Hospital. We analyzed clinical data from UC patients who underwent GMA from February 2015 to May 2023.

Results
The study included 54 patients (30 males and 24 females), with a median age of 48 years and a median disease duration of 2 years. The median Lichtiger-CAI (L-CAI) was 8. There were 43 patients of pancolitis. There were 51 biologics-naïve patients and 3 biologics-experienced patients. Concomitant medications included 5-ASA agents in 21 patients, immunomodulators in 7 patients, and PSL in 31 patients. The median CRP was 1.19 mg/dl and the median albumin was 3.5 g/dl. Adverse events were observed in 3 patients (fatigue, dizziness, palpitations). The median number of GMA sessions was 10, with 33 patients undergoing twice weekly and 9 patients three times weekly. The clinical remission rate was 80% (43/54), and the clinical response rate was 89% (48/54), with a significant improvement in the median L-CAI from 8 to 3 before and after GMA (P<0.001). In the comparison between the PSL concomitant group and the non-PSL group, the clinical remission rate was 83.9% (26/31) in PSL group and 73.9% (17/23) in non-PSLgroup (P=0.369). The clinical response rate was significantly higher in the PSL group (87% (27/31)) than in non-PSL group (52.2% (12/23)) (P=0.004). There was no significant difference in the clinical remission/response rate between the group that underwent GMA twice a week (76.9% (30/39)/84.6% (33/39)) and three times a week (77.8% (7/9)/77.8% (7/9)). In univariate analysis, biologics-naïve was extracted as a contributing factor to clinical remission. The cumulative remission rate at 52 weeks was 72% overall. There was no significant difference in the cumulative remission rate between the PSL group (76.8%) and the non-PSL group (67.6%) (P=0.524). There was also no significant difference between the twice-weekly group (75%) and the three-times-weekly group (57.1%) (P=0.236). Conclusion GMA for UC was found to be useful and safely performed as a remission induction therapy. Concomitant use of PSL increased the clinical response rate. The frequency of GMA showed that three times per week was as effective as two times per week.

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

Eugeni Domènech ¹, Julián Panés ², Joaquín Hinojosa ³, Vito Annese ⁴, Fernando Magro ⁵, Giacomo Carlo Sturniolo ⁶, Fabrizio Bossa ⁷, Francisco Fernández ⁸, Benito González-Conde ⁹, Valle García-Sánchez ¹⁰, Axel Dignass ¹¹, José Manuel Herrera ¹², José Luis Cabriada ¹³, Jordi Guardiola ¹⁴, Maurizio Vecchi ¹⁵, Francisco Portela ¹⁶, Daniel Ginard ¹⁷, J Crohns Colitis. 2018 May 25;12(6):687-694.

In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

https://pubmed.ncbi.nlm.nih.gov/29490024/

Ayumi Ito ¹, Teppei Omori ¹, Norio Hanafusa ¹, Ken Tsuchiya ¹, Shinichi Nakamura ¹, Katsutoshi Tokushige ¹ , J Clin Apher. 2018 Aug;33(4):514-520.

Background: Elderly ulcerative colitis (UC) is increasing. Elderly UC differ from younger UC with respect to the course of their disease. Granulocyte adsorption apheresis (CAP) is often used to treat elderly UC. We retrospectively analyzed the cases of elderly UC who underwent CAP for remission induction therapy in a comparison with younger UC. Methods: 96 patients with UC underwent CAP. Patients who concurrently received tacrolimus, biological agents, or high-dose steroid therapy were excluded. The remaining 80 patients were evaluated. We divided them into an elderly group (aged ≥65 years) and a younger group, and then we compared the groups’ (1) clinical characteristics, (2) the efficacy and adverse effects of CAP, and (3) the complications of PSL. Results: The remission rate was 70.8% in the elderly group and 87.5% in the younger group. There were significant differences between the two groups with respect to the age at the onset of UC, the estimated glomerular filtration rate on admission, underlying diseases, and complications of PSL therapy. Adverse effects of CAP included headache, complications of blood reinfusion, heparin allergy, hypotension, and failure of blood removal. There were significant differences between the two groups with respect to the complications of PSL therapy (all P < .05). Conclusions: Although the elderly group had longer durations of UC, a higher prevalence of underlying diseases, and a higher frequency of adverse events due to PSL therapy, no serious adverse effects of CAP occurred in either group. Thus, CAP was safe and effective in both younger and elderly UC.

https://pubmed.ncbi.nlm.nih.gov/29687913/

Keiichi Tominaga ¹, Masakazu Nakano, Mina Hoshino, Kazunari Kanke, Hideyuki Hiraishi, BMC Gastroenterol. 2013 Mar 1;13:41.

In appropriately selected patients, GMA has significant efficacy with no safety concern. The higher cost of GMA vs PSL should be compromised by good safety profile of this non-pharmacological treatment intervention.

https://pubmed.ncbi.nlm.nih.gov/23452668/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3599731/pdf/1471-230X-13-41.pdf

Keiko Okuma,Kouichi Mitsuishi,Toshio Hasegawa,Hitoshi Tsuchihashi,Hideoki Ogawa,Shigaku Ikeda,

https://doi.org/10.1111/j.1744-9987.2007.00498.x

Abstract: Granulocytapheresis (GCAP) therapy is a newly developed therapeutic modality for inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease. Pyoderma gangrenosum (PG) is a chronic inflammatory skin disease characterized by the appearance of erythematous macules and plaques with pustules or nodules that rapidly progress to ragged, undermined multiple ulcers. We attempted GCAP therapy in a patient with PG resistant to prednisolone and various other immunosuppressants. GCAP therapy was initiated at three- to four-day intervals and a good response from all skin lesions, with eventual total epithelialization, was observed after 10 sessions of this therapy. Furthermore, circulating levels of inflammatory cytokines such as interleukin-8 (IL-8) and granulocyte colony stimulating factor (G-CSF) also decreased after the GCAP therapy. Our results suggest that GCAP is a safe and useful tool for the treatment of intractable PG, and that IL-8 and G-CSF are likely to be involved in the pathogenesis of PG.

https://onlinelibrary.wiley.com/doi/10.1111/j.1744-9987.2007.00498.x