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Use of granulocyte and monocyte adsorption apheresis in dermatology (Review)

Laura Gnesotto 1Guido Mioso 1Mauro Alaibac 1

Exp Ther Med 2022 Jun 24;24(2):536. doi: 10.3892/etm.2022.11463. eCollection 2022 Aug. DOI: 10.3892/etm.2022.11463

Adsorptive granulocyte and monocyte apheresis (GMA) is an extracorporeal treatment that selectively removes activated myeloid lineage leukocytes from peripheral blood. This technique consists of a column with cellulose acetate beads as absorptive leukocytapheresis carriers, and was initially used to treat ulcerative colitis. A literature search was conducted to extract recently published studies about the clinical efficacy of GMA in patients with different skin disorders, reporting information on demographics, clinical symptoms, treatment and clinical course. Dermatological diseases, in which GMA has been performed, include generalized pustular psoriasis, pyoderma gangrenosum, palmoplantar pustular psoriasis, Behcet’s disease, Sweet’s syndrome, adult-onset Still’s disease, impetigo herpetiformis, reactive arthritis, acne and hidradenitis suppurativa syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus. In most patients, GMA was started after the failure of conventional therapeutic options and it was helpful in the majority of cases. Based on the information summarized, GMA could be considered a valid non-pharmacological treatment option for patients with several dermatological conditions, which are difficult to treat with other pharmacological preparations.

 PASH syndrome; cutaneous allergic vasculitis; granulocyte and monocyte apheresis; neutrophilic dermatoses; reactive arthritis; systemic lupus erythematosus.

https://pubmed.ncbi.nlm.nih.gov/35837066/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257973/

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Granulocyte and monocyte/macrophage apheresis for the treatment of immune-mediated inflammatory arthropathies: case reports

Carro Martínez AV, Montolio Chiva L, Robustillo Villarino M. Drugs Context. 2021;10:2021-8-5. https://doi.org/10.7573/dic.2021-8-5

Drug therapy of immune-mediated inflammatory arthropathies is not always satisfactory, and there is a risk of adverse events. Granulocyte and monocyte/macrophage apheresis (GMA) is a non-pharmacological therapeutic option that is beneficial and very well tolerated. GMA involves passing blood through a column with cellulose acetate beads to remove increased and activated myeloid lineage cells and improve the cytokine profile. The technique reduces pain and inflammation. We present four clinical reports that illustrate the clinical uses of GMA with the medical device Adacolumn® in patients with different backgrounds and immune-mediated inflammatory arthritis. The results were positive, and no adverse events were reported..

dic.2021-8-5.pdf (drugsincontext.com)

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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

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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

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Successful treatment of plaque-type psoriasis by granulocyte and monocyte adsorption apheresis in a patient with psoriatic arthritis

Atsuko Matsuoka 1Yuko Higashi 1Takuro Kanekura 1 , J Dermatol 2018 Nov;45(11):e324-e325

The combined efficacy of adalimumab with GMA on UC patients can improve the clinical curative efficacy, effectively reduce the inflammatory factors, which is beneficial to the repair of intestinal mucosal barrier function, and worthy of clinical application.

https://pubmed.ncbi.nlm.nih.gov/29740866/

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Therapeutic depletion of myeloid lineage leukocytes by adsorptive apheresis for psoriatic arthritis: Efficacy of a non-drug intervention for patients refractory to pharmacologics

Psoriatic arthritis (PsA), a chronic inflammatory arthropathy associated with psoriasis, is an intractable immune disorder and refractory to pharmacological intervention. We assessed efficacy of selective depletion of myeloid lineage leukocytes in patients with PsA in a multicenter setting. A total of 20 patients with moderate to severe PsA refractory to conventional and biological disease-modifying antirheumatic drugs were included. Eligible patients had 3 points or more in the classification criteria for PsA. Each patient received five sessions, once a week, of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn® . The primary efficacy outcome was 20% or more decrease in the American College of Rheumatology score 20 (ACR20). Partial responders could receive an additional five GMA sessions. Of 20 patients, two did not complete the study, nine responded to five GMA sessions and nine 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 seven of 10 (70%) and five 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 study demonstrates that GMA with the Adacolumn was effective with good safety profile in patients with PsA refractory to pharmacologicals. The results indicate a major role for myeloid leukocytes in the immunopathogenesis of PsA. A large controlled study is warranted to fully evaluate the efficacy of Adacolumn GMA in patients with PsA.

Takuro Kanekura 1Mariko Seishima 2Masaru Honma 3Takafumi Etou 4Hikaru Eto 5Keiko Okuma 6Yukari Okubo 7Yukie Yamaguchi 8Takeshi Kambara 9Tomotaka Mabuchi 10Yasushi Suga 11Akimichi Morita 12Kiyofumi Yamanishi 13Daisuke Tsuruta 14Kei Itoh 15Ken Yamaji 16Shigaku Ikeda 6

J Dermatol 2017 Dec;44(12):1353-1359. doi: 10.1111/1346-8138.13975. Epub 2017 Aug 3.

Psoriatic arthritis (PsA), a chronic inflammatory arthropathy associated with psoriasis, is an intractable immune disorder and refractory to pharmacological intervention. We assessed efficacy of selective depletion of myeloid lineage leukocytes in patients with PsA in a multicenter setting. A total of 20 patients with moderate to severe PsA refractory to conventional and biological disease-modifying antirheumatic drugs were included. Eligible patients had 3 points or more in the classification criteria for PsA. Each patient received five sessions, once a week, of adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn® . The primary efficacy outcome was 20% or more decrease in the American College of Rheumatology score 20 (ACR20). Partial responders could receive an additional five GMA sessions. Of 20 patients, two did not complete the study, nine responded to five GMA sessions and nine 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 seven of 10 (70%) and five 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 study demonstrates that GMA with the Adacolumn was effective with good safety profile in patients with PsA refractory to pharmacologicals. The results indicate a major role for myeloid leukocytes in the immunopathogenesis of PsA. A large controlled study is warranted to fully evaluate the efficacy of Adacolumn GMA in patients with PsA.

https://pubmed.ncbi.nlm.nih.gov/28771892/

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Combination Therapy of Infliximab and Granulocyte/Monocyte Adsorption Apheresis for Refractory Pustular Psoriasis with Psoriatic Arthritis

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Granulocyte and monocyte adsorption apheresis (GCAP) for refractory skin diseases caused by activated neutrophils and psoriatic arthritis: evidence that GCAP removes Mac-1-expressing neutrophils

Takuro Kanekura 1Katsuya HiraishiKoichi KawaharaIkuro MaruyamaTamotsu Kanzaki

Ther Apher Dial 2006 Jun;10(3):247-56. doi: 10.1111/j.1744-9987.2006.00369.x.

In the present study, we have shown that granulocyte and monocyte adsorption apheresis (GCAP), an extracorporeal apheresis instrument whose column contains cellulose acetate (CA) beads, is useful for skin diseases attributable to activated granulocytes and psoriatic arthritis (PsA). We assessed the clinical effectiveness of GCAP and investigated the mechanisms underlying the adsorption of pathogenic granulocytes. The effect of GCAP was assessed in 14 patients with neutrophilic dermatoses and 16 with PsA. The mechanisms by which the instrument adsorbs activated granulocytes were investigated using an in vitro mini-column system that mimics the GCAP. Skin lesions and arthropathy improved in 22 of 29 patients (75.9%) and 14 of 18 (77.8%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral neutrophils, increased compared with normal subjects, was reduced by GCAP. In the mini-column system, CA beads adsorbed 50% neutrophils; and adsorption was inhibited significantly by treating plasma with EDTA and blood cells with antihuman CD11b monoclonal antibody. GCAP was useful for treating neutrophilic dermatoses and PsA. GCAP adsorbs Mac-1-expressing neutrophils to the CA beads by the binding of complement component (iC3b) on CA beads and CD11b expressed on activated neutrophils.

https://pubmed.ncbi.nlm.nih.gov/16817789/

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Treatment of psoriatic arthritis with granulocyte and monocyte adsorption apheresis

Takuro Kanekura 1Hisashi KawabataIkuro MaruyamaTamotsu Kanzaki

J Am Acad Dermatol  2004 Feb;50(2):242-6. doi: 10.1016/s0190-9622(03)02474-5.

Granulocyte and monocyte adsorption apheresis (GCAP) is a new extracorporeal apheresis treatment modality that removes pathogenic granulocytes. Recently, we found that GCAP is useful for treating pyoderma gangrenosum and pustular psoriasis. We thought that this treatment may also be effective for treating other disorders attributable to activated granulocytes and studied the efficacy of GCAP in 4 patients with psoriatic arthritis. Treatment with GCAP resulted in remarkable clearing of joint pain, suggesting that GCAP is valuable for treating arthritis as well as skin disorders. We present a detailed description of these patients and this novel therapy.

https://pubmed.ncbi.nlm.nih.gov/14726879/

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