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

Yuko Higashi, Munekazu Yamakuchi, Takuro Kanekura

poster at ISFA 2019 pag 126

Neutrophilic skin diseases are a group of disorders characterized by intense dermal infiltration of neutrophils without infection. They include a variety of diseases, such as pyoderma gangrenosum, pustular psoriasis, and palmoplantar pustulosis. We demonstrated that granulocyte and monocyte adsorption apheresis (GMA) is a useful treatment modality for such refractory skin diseases. Microarray analysis of microRNAs (miRNAs) was performed using sera of patients with neutrophilic skin diseases before and after GMA. Several miRNAs significantly increased in patients compared to control subjects. The expression of three
miRNAs decreased after apheresis, suggesting that these miRNAs might be involved in the pathogenesis of neutrophilic skin decreases. To prove the function of these miRNAs, HL-60, a human acute promyelocytic leukemia cell line, was differentiated by the treatment of alltrans retinoic acid (ATRA). When HL-60 was differentiated to neutrophilic cells, the HEstaining shows an increased cytoplasm to nucleus ratio, condensated chromatin, and nuclear segmentation. The expression of three miRNAs increased during the neutrophilic differentiation. Stimulation of ATRA-treated HL-60 by some cytokines altered miRNA expressions. Moreover, manipulation of these miRNAs changed proliferation of cultured keratinocytes. These data
suggest that miRNAs play an important role in regulating neutrophilic differentiation and proliferation of keratinocytes in case of neutrophilic disorders such as psoriasis. These miRNAs could be markers of disease severity and response of GMA.

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

Miho Hatanaka, Yuko Higashi, Takuro Kanekura

poster at ISFA 2019 pag 104

Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and
systemic flushing accompanied by extensive sterile pustules. Treatments of GPP are usually
topical corticosteroids, activated vitamin D3 ointment, ultraviolet light (UV) therapy, and
oral administration of etretinate, cyclosporine, or methotrexate. Recently, biologics such as
TNF- α; inhibitors, anti-IL-17- and anti-IL-23 antibodies are used. Pustulosis palmoplantaris
(PPP) is a chronic recurrent disorder of the palms and soles characterized by sterile intradermal
pustules. PPP often accompanies joint symptoms. In some instances, PPP is associated with
a focus of infection somewhere in the body; elimination of the infection sometimes improve
symptom. Some treatments of GPP are used for PPP. Psoriatic arthritis (PsA) is a disease
characterized by skin and nail psoriasis together with widespread musculoskeletal inflammation
such as peripheral joint disease, axial joint disease, enthesitis, and dactylitis. Treatment of
PsA is oral administration of NSAID’s, cyclosporine, methotrexate and phosphodiesterase 4
inhibitors for mild to moderate cases. Biologics; TNF- αinhibitors, anti-IL-17- and anti-IL-23
antibodies; have been approved for severe or advanced cases. Granulocyte/monocyte adsorption
apheresis (GMA) is an extracorporeal therapy designed to remove and suppress the functions
of neutrophils, macrophages and monocytes that accumulate in the inflamed tissue and are
involved in the pahogenesis. GMA may be considered as a safe treatment modality with few
side-effects for GPP, PPP and PsA. The effect and safety of GMA have been reported mostly in
case reports. Although the effect and safety of GMA were demonstrated in a multicenter study.
GMA’s utility is expected based on the mechanism of action.

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

Takuro Kanekura

poster at ISFA 2019 pag 58

Adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn is an extracorporeal treatment, which uses cellulose acetate (CA) beads as adsorptive leucocytapheresis carriers designed to remove elevated and potentially activated myeloid lineage leucocytes. Case series studies on the clinical effectiveness of GMA on skin diseases and associated arthropathy attributable to activated myeloid lineage leucocytes returned remarkable outcome without any serious adverse events. Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis. PsA is an intractable immune disorder and refractory to pharmacological intervention. Efficacy of selective depletion of myeloid lineage leucocytes in patients with PsA was assessed.in a multicenter setting. A total of 20 patients with moderate to severe PsA refractory to conventional and biological disease-modifying antirheumatic drugs were enrolled. Each patient received 5 sessions of GMA once a week. The primary efficacy outcome was 20% or more decrease in the American College of Rheumatology score 20 (ACR20). Partial responders received an additional 5 GMA sessions. Of 20 patients, 2 did not complete the study, 9 responded to 5 GMA sessions and 9 received 10 sessions. At the first evaluation 2 weeks after the last GMA session, 13 of the 20 (65.0%) patients achieved ACR20. ACR20 was maintained in 7 of 10 (70%) and 5 of 10 (50%) patients at the follow-up evaluation points 8 and 20 weeks after the last GMA session, respectively. GMA was well tolerated without any safety concern. This multicenter study demonstrated that GMA was effective with good safety profile in patients with PsA refractory to pharmacologicals, We present the results of this study and mode of action of GMA.

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

Axel Dignass ¹, Ayesha Akbar ², Daniel C Baumgart ³, Gilles Bommelaer ⁴, Guillaume Bouguen ⁵, Guillaume Cadiot ⁶, Anton Gillessen ⁷, Jean-Charles Grimaud ⁸, Ailsa Hart ², Syed Hoque ⁹, Richard Makins ¹⁰, Christophe Michiels ¹¹, Jacques Moreau ¹², Purushothaman Premchand ¹³, Wolfgang Ramlow ¹⁴, Stefan Schanz ¹⁵, Sreedhar Subramanian ¹⁶, Christian von Tirpitz ¹⁷, Bruno Bonaz ¹⁸ , Scand J Gastroenterol. 2018 Apr;53(4):442-448.

This study confirms findings of the 12-week interim analysis and demonstrates that GMA apheresis provides a safe and beneficial long-term outcome for patients with chronic active UC resistant/intolerant to IS and/or TNF inhibitors.

https://pubmed.ncbi.nlm.nih.gov/29513111/

Axel Dignass ¹, Ayesha Akbar ², Ailsa Hart ², Sreedhar Subramanian ³, Gilles Bommelaer ⁴, Daniel C Baumgart ⁵, Jean-Charles Grimaud ⁶, Guillaume Cadiot ⁷, Richard Makins ⁸, Syed Hoque ⁹, Guillaume Bouguen ¹⁰, Bruno Bonaz ¹¹ , J Crohns Colitis. 2016 Jul;10(7):812-20. 

At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgroup.

https://pubmed.ncbi.nlm.nih.gov/26818659/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955912/pdf/jjw032.pdf

Satoshi Tanida ¹, Tsutomu Mizoshita ¹, Hirotada Nishie ¹, Keiji Ozeki ¹, Takahito Katano ¹, Eiji Kubota ¹, Hiromi Kataoka ¹, Takeshi Kamiya ¹, Takashi Joh ¹ , J Clin Med Res. 2015 Nov;7(11):884-9.

It was concluded that combination therapy with ADA plus intensive GMA is useful for induction of clinical remission in refractory UC patients, and is well tolerated.

https://pubmed.ncbi.nlm.nih.gov/26491502/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596271/pdf/jocmr-07-884.pdf

Tomotaka Mabuchi ¹, Yasuaki Manabe, Hanako Yamaoka, Tami Ota, Masayuki Kato, Norihiro Ikoma, Yoshiyuki Kusakabe, Hirotaka Komaba, Akira Ozawa, J Dermatol. 2014 Jun;41(6):521-4.

 During maintenance HD twice a week, weekly GMA was started at Tokai University Hospital. The skin symptoms disappeared after five administrations of GMA. We suggest that GMA is an effective therapy for GPP patients with ESRD who are treated with HD.

https://pubmed.ncbi.nlm.nih.gov/24815562/