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)

Mauro Mastronardi ¹, Elisabetta Cavalcanti ², Nunzia Labarile ¹, Raffaele Armentano ³, Francesco Gabriele ⁴, Margherita Curlo ¹ Ther Adv Chronic Dis. 2023 Nov 3:14:20406223231194190.

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn’s disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.

Pyoderma gangrenosum in ulcerative colitis patient treated with vedolizumab: adsorptive granulocyte/monocyte apheresis as a new therapeutic option refractory cases – a case report and literature review – PubMed (nih.gov)

Pyoderma gangrenosum in ulcerative colitis patient treated with vedolizumab: adsorptive granulocyte/monocyte apheresis as a new therapeutic option refractory cases – a case report and literature review – PMC (nih.gov)

Satoshi Tanida

poster at ISFA 2019 pag 56

Background and Aim: A monotherapy with intensive GMA, biologics or a JAK inhibitor are limited in patients with intractable Crohn’s disease (CD) or ulcerative colitis (UC). We retrospectively evaluated the 10- and 52-week efficacy and safety of combination therapy of intensive GMA with biologics or a JAK inhibitor for intractable UC or CD.
Method: A combination of intensive GMA (2 sessions a week, total 10 times) with tofacitinib (TOF) for active UC was performed and that of intensive GMA with ustekinumab (UST) for active CD was done. Results: Of 6 consecutive UC patients receiving a combination therapy of TOF (20 mg daily for 8 weeks as induction therapy and subsequently 10 mg daily) plus intensive GMA for moderately-to-severely active UC and loss of response to corticosteroids, azathioprine, and/ or biologic therapies, 67% (4 cases) displayed clinical remission according to Mayo score and 100% displayed mucosal healing at 10 weeks. A temporary increase in CPK were seen. Of 5 consecutive CD patients receiving a combination therapy of ustekinumab (every 8 weeks) plus intensive GMA for moderately-to-severely active CD and loss of response to corticosteroids, azathioprine, and/or biologic therapies, 75% displayed cumulative steroid-free clinical remission at 10 weeks and did such remission over 52 weeks under subsequent maintenance monotherapy of UST. The mean CDAI at baseline were 257. Its values at 10 and 52 weeks after the combination therapy with UST plus intensive GMA were 48 and 68, respectively. One case showed mucosal healing at 52 weeks according to SES-CD. No adverse events were observed. Conclusions: Combination therapy of intensive GMA with biologics or a JAK inhibitor appeared to be effective and safe for refractory UC or CD.

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

Premchand P, Ford L, Venkama DPWE-236 White cell aphaeresis (WCA) with adacolumn is effective in selected cases of chronic refractory colitis with high histological activityGut 2012;61:A394.

Introduction Treatment options for patients with chronic refractory colitis are limited. White cell aphaeresis (WCA) is effective in inducing clinical remission in chronic refractory colitis in patients with a strong inflammatory burden at baseline and histologically active disease. Previous multinational sham controlled trials have demonstrated significant improvement when patients with high histological activity (modified Rileys score) are selected for treatment. Methods A prospective study was conducted in 30 patients with severe steroid -dependent or steroid -refractory ulcerative colitis referred for WCA. Inclusion criteria were (i) High disease activity score (partial Mayo score ≥6) (ii) Intractable symptoms despite treatment with steroids and/or immunosuppressants (iii) Severe disease at endoscopy and histologically. The aim was to induce clinical and IBD-Q remission at 12 weeks. A Mayo score ≤3 defined clinical remission. The 32 item Inflammatory Bowel Disease questionnaire (IBD-Q) was used to assess quality of life prior to treatment and at 12 weeks. Results Patient Characteristics: Prior to treatment 28 patients (93.3%) were prescribed 5-ASA compounds. 12 patients (40%) were prescribed topical therapies (5-ASA enemas or suppositories/steroids enemas). 27 patients (90%) were steroid dependent (Prednisolone mean dose 21.1 mg, median 20 mg). Three patients (10%) were steroid refractory (no response to high dose oral steroids). 13 patients (43.3%) were prescribed Azathioprine of the remainder all had documented intolerance or a contraindication. One patient (3.3%) was prescribed six Mercaptopurine. Five patients had failed Infliximab (16.6%) and in one patient (3.3%) it was contraindicated. 1 patient (3.3%) had failed intramuscular Methotrexate. Outcomes: At week 12 clinical remission (Mayo score ≤3) was achieved in 22 patients (73.3%), 18 patients (60%) were no longer prescribed oral steroids. IBD-Q remission at week 12 was achieved in 19 patients (63.3%). Of the remainder, five patients (16.6%) achieved an IBD-Q response. Of eight patients (26.6%) who failed to achieve clinical remission at 12 weeks, one achieved delayed remission at 20 weeks. Of the remaining seven treatment failures, five underwent colectomy (16.6%). Conclusion WCA can be effective in inducing clinical remission and improving quality of life (IBD-Q) indices in chronic severe steroid refractory ulcerative colitis with highly active disease histologically. This data series suggests WCA should be considered before colectomy in this challenging patient group

https://gut.bmj.com/content/61/Suppl_2/A394.1.info

P. Gonzalez Carro, F. Perez Roldan, O. Roncero Garcıa Escribano,R. Lafuente, M.L. Legaz Huidobro, and A. Amigo Echenagusıa

Journal of Clinical Apheresis 21: 249–251 (2006)

To our knowledge, no cases of combined therapy with infliximab and granulocyte apheresis have been previously reported. Our results suggest that this combined therapy is a possible alternative to treat CD patients in the event of loss of response to infliximab.

https://onlinelibrary.wiley.com/doi/10.1002/jca.20093

Yoshihiro Fukuda ¹, Toshiyuki Matsui, Yasuo Suzuki, Kazunari Kanke, Takayuki Matsumoto, Masakazu Takazoe, Takayuki Matsumoto, Satoshi Motoya, Terasu Honma, Koji Sawada, Tsuneyoshi Yao, Takashi Shimoyama, Toshifumi Hibi, J Gastroenterol
. 2004 Dec;39(12):1158-64. doi: 10.1007/s00535-004-1465-z.

GCAP could be effective for inducing remission and improving quality of life in patients with active CD that is refractory to conventional therapy.

https://pubmed.ncbi.nlm.nih.gov/15622479/

Purushothaman Premchand ¹, Ken Takeuchi, Ingvar Bjarnason Eur J Gastroenterol Hepatol 2004 Sep;16(9):943-5. doi: 10.1097/00042737-200409000-00023.

Refractory ulcerative colitis that fails conventional intense medical treatment often leads to colectomy. Although ciclosporin and infliximab may avert colectomy in certain cases, these treatments come with substantial toxicity and may only act as a bridge to avert emergency surgery. Granulocyte monocyte/macrophage adsorption apheresis is a new treatment and has shown efficacy for refractory colitis in up to 80% of cases in a Japanese study and is apparently only associated with negligible side effects. We report a case of severe refractory proctitis destined for colectomy effectively treated with granulocyte monocyte/macrophage adsorption apheresis. After two of five sessions the patient achieved full clinical remission, which has been sustained with the addition of azathioprine for more than 1 year.

https://pubmed.ncbi.nlm.nih.gov/15316424/

Abby R Saniabadi ¹, Hiroyuki Hanai, Ken Takeuchi, Kazuo Umemura, Mitsuyoshi Nakashima, Taro Adachi, Chikako Shima, Ingvar Bjarnason, Robert Lofberg, Ther Apher Dial. 2003 Feb;7(1):48-59.

Apheresis has been recognized both economically and therapeutically as a novel approach for the treatment of inflammatory diseases, and certain others, which respond poorly to drug therapy. This report is about Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device with a volume of 335 mL, filled with about 220 g of cellulose acetate beads of 2 mm diameter as the column adsorptive carriers. Pre- and post-column leukocyte counts have shown that the carriers adsorb about 65% of granulocytes, 55% of monocytes and 2% of lymphocytes from the blood in the column. Additionally, after apheresis, there is a marked decrease in inflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and IL-8) produced by blood leukocytes, together with down-modulation of L-selectin and the chemokine receptor CXCR3. Adacolumn has been used to treat patients with rheumatoid arthritis, ulcerative colitis and HIV infection. Typical apheresis sessions have been 4-10, at a frequency of one or two sessions per week. Treatment of patients with Adacolumn has been associated with very promising efficacy and safety data. Accordingly, in Japan, Adacolumn has been approved by the Ministry of Health for the treatment of ulcerative colitia. Furthermore, Adacolumn met the required quality and safety standards for medical devices and received an EC certification (CE-mark) from TUV in 1999. However, although Adacolumn carriers are very efficient in depleting excess and activated granulocytes and monocytes/macrophages, the clinical efficacy associated with Adacolumn apheresis cannot be fully explained on the basis of reducing granulocytes and monocytes per se. Hence, a long lasting effect on inflammatory cytokine generation, chemokine activities or immunomodulation is likely, but the precise mechanisms involved are not fully understood yet.

https://pubmed.ncbi.nlm.nih.gov/12921115/