Scientific corner

Refractory Ulcerative Colitis Improved by Scheduled Combination Therapy of Vedolizumab and Granulocyte and Monocyte Adsorptive Apheresis

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

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Combination Therapy With Tofacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction Therapy for Refractory Ulcerative Colitis

Satoshi Tanida 1Keiji Ozeki 1Tsutomu Mizoshita 1Mika Kitagawa 1Takanori Ozeki 1Mamoru Tanaka 1Hirotada Nishie 1Takaya Shimura 1Eiji Kubota 1Hiromi 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

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SA6-03 MicroRNA and granulocyte and monocyte adsorption apheresis on neutrophilic skin diseases

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

Scientific corner

GS2-03 Japanese apheresis guidelines for the management and treatment of generalized pustular psoriasis, pustulosis palmoplantaris and psoriasis arthropathica

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

Scientific corner

GS1-04 The apheresis guidelines for digestive diseases

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

Scientific corner

Granulocyte and monocyte adsorption apheresis for psoriatic arthritis

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

Scientific corner

Granulocyte/monocyte adsorptive apheresis for the treatment of therapy-refractory chronic active ulcerative colitis

Axel Dignass 1Ayesha Akbar 2Daniel C Baumgart 3Gilles Bommelaer 4Guillaume Bouguen 5Guillaume Cadiot 6Anton Gillessen 7Jean-Charles Grimaud 8Ailsa Hart 2Syed Hoque 9Richard Makins 10Christophe Michiels 11Jacques Moreau 12Purushothaman Premchand 13Wolfgang Ramlow 14Stefan Schanz 15Sreedhar Subramanian 16Christian von Tirpitz 17Bruno 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/

Scientific corner

Safety and efficacy of granulocyte/monocyte apheresis in steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics (ART trial): 12-week interim results.

Axel Dignass 1Ayesha Akbar 2Ailsa Hart 2Sreedhar Subramanian 3Gilles Bommelaer 4Daniel C Baumgart 5Jean-Charles Grimaud 6Guillaume Cadiot 7Richard Makins 8Syed Hoque 9Guillaume Bouguen 10Bruno 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

Scientific corner

Combination Therapy With Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Refractory Ulcerative Colitis.

Satoshi Tanida 1Tsutomu Mizoshita 1Hirotada Nishie 1Keiji Ozeki 1Takahito Katano 1Eiji Kubota 1Hiromi Kataoka 1Takeshi Kamiya 1Takashi 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

Scientific corner

Case of generalized pustular psoriasis with end-stage renal disease successfully treated with granulocyte monocyte apheresis in combination with hemodialysis.

Tomotaka Mabuchi 1Yasuaki ManabeHanako YamaokaTami OtaMasayuki KatoNorihiro IkomaYoshiyuki KusakabeHirotaka KomabaAkira 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/

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