Rie Shukuin ¹, Haruka Koizumi ¹, Aoi Ebata ¹, Satoko Imai ¹, Yuta Yamashita ¹, Mariko Ogawa-Momohara ¹, Takuya Takeichi ¹, Yoshinao Muro ¹, Norito Takami ², Masashi Akiyama ¹

J Dermatol. 2023 Jun;50(6):e181-e182.

Successful combination therapy of bimekizumab and granulocyte monocyte adsorption apheresis for generalized pustular psoriasis complicated with microscopic polyangiitis – PubMed (nih.gov)

Nobuhiro Ueno Seisuke Saito Masahiro Sato Yuya Sugiyama doi: 10.21203/rs.3.rs-3037827/v1

Background: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn was given to patients with active Crohn’s disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with active CD remains unclear. Methods: This multicenter retrospective cohort study encompassed patients with CD who underwent GMA in seven independent institutions in Japan from January 2010 to March 2023. All clinical data were obtained from medical records. This study aimed to evaluate the clinical efficacy, safety, and subsequent clinical progression after GMA in patients with CD. Result: This study enrolled 173 patients with active inflammatory bowel disease who underwent GMA with Adacolumn, and among them, 16 patients with CD with mild to moderate disease activity were analyzed. Concomitant medication, including steroids, immunomodulators, and biologics, was used in 93.7% of all cases. The overall remission and response rates were 25.0% and 68.8%, respectively. The response rate between groups concerning the frequency and total GMA sessions revealed no significant difference. Six (37.5%) patients experienced adverse events (AEs). All AEs were related to the trouble in blood access and recovered soon without any sequelae. Regarding the factors associated with response to GMA, the responder group had a significantly longer disease duration (336 vs 44 months, p = 0.036) and exhibited a relatively lower rate of intestinal strictures and a median score of a simple endoscopic score for CD (SES-CD) (9.1 vs 60 %, p = 0.063 and 10 vs 21.5, p = 0.091, respectively). Further, all patients responding to GMA received biologics that were continuously used before and after GMA. Furthermore, 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to anti-tumor necrosis factor-α agent. Conclusion: Therefore, GMA may exhibit heightened effectiveness in patients with moderately active CD without severe endoscopic activity. Moreover, it represents a potential novel therapeutic option for refractory CD, particularly with insufficient response to biologics.

(PDF) The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn’s disease: A multicenter retrospective cohort study (researchgate.net)

Yuki Noguchi ¹, Keiji Shimazu ², Teruhiko Totani ¹, Kazumasa Komura ³, Atsuo Tanaka ² Transfus Apher Sci. 2023 Apr;62(2):103581. doi: 10.1016/j.transci.2022.103581

Granulocyte monocyte adsorption (GMA) is considered one of the modalities for the remission induction of ulcerative colitis (UC). We previously reported that single-needle GMA (SN-GMA) could simplify the GMA. In the present study, the efficiency of SNGMA was examined according to the administration of corticosteroids (PSL) in UC patients. Blood sample were taken at proximal and distal side of the column during the SN-GMA treatment. Disease activity score (partial Mayo score: pMayo score) before and after the SN-GMA was investigated. The data of 18 patients with active UC (11 and 7 patients with PSL naïve and PSL use groups, respectively) treated with SN-GMA was analyzed. The mean pMayo score before the GMA treatment was comparable between the PSL naïve group (p = 0.26), whereas the score after the GMA treatment was significantly lower in PSL naïve group (0.8 + 0.6) than in PSL use group (3.0 + 2.1) (p = 0.04). Patients achieving the clinical remission were more observed in the PSL naive group (90.9%) than in the PSL use group (42.9%) (p = 0.047). The adsorption efficiency in the PSL naïve and PSL use groups were as follows: leukocytes (34.45 ± 7.43% vs 23.14 ± 7.56%: p = 0.008), granulocytes (41.74 ± 10.07% vs 27.99 ± 15.11%: p = 0.04), monocytes (32.59 ± 24.07% vs 33.16 ± 24.18%: p = 0.95), and lymphocytes (-1.87 ± 18.17% vs -3.79 ± 22.52%: p = 0.84), with a significant difference of the absorption efficiency in leukocytes and granulocytes. These data collectively indicate that the SN-GMA can be applied for the remission induction to active UC patients with a higher clinical remission rate in PSL naïve patients compared to PSL use patients.

Comparison of adsorption efficiency of leukocytes in single needle GMA with or without PSL treatment in patients with active ulcerative colitis – PubMed (nih.gov)

Comparison of adsorption efficiency of leukocytes in single needle GMA with or without PSL treatment in patients with active ulcerative colitis – Transfusion and Apheresis Science (trasci.com)

Satoshi Tanida ^1 2, Keiji Ozeki ³, Takahito Katano ³, Mamoru Tanaka ³, Takaya Shimura ³, Eiji Kubota ³, Hiromi Kataoka ³, Takuya Takahama ², Shun Sasoh ², Yoshimasa Kubota ², Tesshin Ban ², Tomoaki Ando ², Makoto Nakamura ², Takashi Joh ²J Clin Med Res. 2023 Mar;15(3):181-186. doi: 10.14740/jocmr4887

Every-week (ew) adalimumab (ADA) maintenance following induction therapy with a standard induction regimen has recently been approved for use in Japan. The efficacy and safety of combination therapy with ew-ADA maintenance following standard induction regimen plus intensive granulocyte and monocyte adsorptive apheresis (GMA) (two sessions/week) for the treatment of refractory ulcerative colitis (UC) displaying failure of conventional, biologics and Janus kinase inhibitor have not been evaluated previously. The present retrospective study evaluated the 10-week efficacy of this combination therapy among refractory UC patients. Six patients were given initial ADA combination therapy (ADA at 160 mg in week 0, ADA 80 mg in week 2, and 40 mg in week 4, followed by ew-ADA at 40 mg/week) plus intensive GMA. One patient (16.6%) achieved clinical remission and two patients (33.3%) achieved endoscopic improvement by week 10. After excluding two patients who discontinued treatment, mean full Mayo score (P = 0.14), endoscopic subscore (P = 0.18) and C-reactive protein level (P = 0.27) at 10 weeks were numerically decreased compared with baseline in the remaining four cases, although the differences were not significant. Use of ew-ADA maintenance following standard induction regimen plus intensive GMA appears unlikely to achieve satisfactory induction of clinical remission in UC patients for whom conventional agents, biologics and Janus kinase inhibitors have failed.

Induction Therapy With a Combination of Weekly Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Ulcerative Colitis and Failure of Conventional Agents, Biologics and Janus Kinase Inhibitor – PubMed (nih.gov)

Induction Therapy With a Combination of Weekly Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Ulcerative Colitis and Failure of Conventional Agents, Biologics and Janus Kinase Inhibitor – PMC (nih.gov)

Yoshikazu Tsuzuki, Rie Shiomi, Hisashi Matsumoto, Kazuya Miyaguchi, Takeru Kusano, Hideki Ohgo, Hidetomo Nakamoto, Hiroyuki Imaeda J. Clin. Biochem. Nutr. 2023, 72 (1): 68-73.

Several new treatments for ulcerative colitis have been developed recently. The depletion of leukocytes by granulocyte and monocyte adsorption apheresis (GMA) was developed and adapted for patients with ulcerative colitis with rare adverse events. We investigated whether treatment with GMA and prednisolone (GMA + PSL) is more effective than PSL alone for patients with moderate to severe ulcerative colitis. Forty-seven patients with moderate to severe ulcerative colitis were retrospectively analyzed. Among the 47 patients, 27 received PSL, while 20 received GMA + PSL. The clinical activity of ulcerative colitis was evaluated using the Lichtiger clinical activity index (CAI) and serum levels of C-reactive protein. Mayo endoscopic score (MES) was used to examine endoscopic activity. The clinical remission rate was significantly higher in the GMA + PSL group than in the PSL group (65% vs 29.6%, p = 0.0206). The mucosal healing rate was also significantly higher in the GMA + PSL group than in the PSL group (60% vs 26%, p = 0.0343). The combination of GMA and steroids may be more effective than steroids alone for inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

JCM | Free Full-Text | An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis (mdpi.com)

ja (jst.go.jp)

Alvise Sernicola ¹,Anna Colpo ²,Anca Irina Leahu ² and Mauro Alaibac ¹Medicina 2022, 58(10), 1398; https://doi.org/10.3390/medicina58101398

In the field of advanced melanoma, there is an urgent need to investigate novel approaches targeting specific components of the cancer–immunity cycle beyond immune checkpoint inhibitors. The authors reviewed the basic understanding of the role of neutrophils in cancer biology, and the latest clinical evidence supporting the correlation between cancer-associated neutrophils and the prognosis and response to the immunotherapy of advanced melanoma. Finally, they propose that granulocyte and monocyte apheresis, an emerging non-pharmacological treatment in current dermatology, could become an investigative treatment targeting melanoma-associated neutrophils which could be potentially used in combination with the usual immune checkpoint inhibitors.

https://www.mdpi.com/1648-9144/58/10/1398

Keiki Shimada, Daisuke Katagiri, Aika Kato, Naoto Nunose, Motohiko Sato, Yuri Katayama, Kanako Terakawa, Takahito Niikura, Emi Sakamoto, Yuki Yoshizaki, Minami Suzuki, Takashi Fukaya, Takeshi Tamaki & Hideki Takano Ren Replace Ther 8, 50 (2022). https://doi.org/10.1186/s41100-022-00439-y

Background Generalized pustular psoriasis (GPP) usually presents with fever, generalized flushing, and multiple sterile pustules on the skin, which histopathologically form subcorneal pustules characterized by Kogoj spongiform pustules. Granulocyte/monocyte adsorption apheresis (GMA) was approved in Japan in 2012. The use of biologics for psoriasis treatment is increasing. Several case reports have evaluated the combination of GMA and cyclosporine (CyA) for GPP. However, very few English reports on combining biologics and GMA in treating GPP exist. Case presentation A 79-year-old man with a history of hypertension, diabetes mellitus, chronic kidney disease, and atrial fibrillation was admitted. He had been consulting a dermatologist for psoriasis vulgaris (PV) since the age of 44. The patient was diagnosed with severe GPP and treated with 300 mg secukinumab (SEC) on day 3. SEC is a fully human monoclonal IgG1 antibody that targets IL-17A. Five doses were administered. In addition, GMA was administered once a week, three times from day 4. After the first administration of GMA, the inflammatory response and skin condition improved markedly. The patient was discharged from the hospital on day 34. Conclusions The present study is the first English-written report on the combined administration of SEC and GMA both instituted since admission for severe GPP, with immediate patient response to treatment. Notably, IL-17A plays a vital role in the pathogenesis of GPP. GMA can eliminate activated leukocytes, and the early introduction of combined IL-17 monoclonal antibody and GMA may allow disease suppression in patients with severe GPP, thus avoiding progression to multiorgan failure. Further studies may verify the effects of IL-17 monoclonal antibodies and GMA on severe GPP.

https://rrtjournal.biomedcentral.com/articles/10.1186/s41100-022-00439-y#citeas

Giorgos Bamias ¹, Evanthia Zampeli ², Eugeni Domènech ³ Expert Rev Gastroenterol Hepatol  2022 Jul 19;1-15. doi: 10.1080/17474124.2022.2100759.

Introduction: Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract comprising Crohn’s disease (CD) and ulcerative colitis (UC). While any part of the digestive tract can be affected in CD, mucosal inflammation in UC is limited to the colon. Differences and similarities between the two conditions are reflected by their pathophysiology. Areas covered: An overview of immunological aspects, pharmacological management, and biomarkers of IBD is provided. The role of adsorptive granulocyte and monocyte apheresis (GMA) is reviewed including its primary and secondary effects on the immune system, as well as clinical studies in IBD (mainly UC), and potential biomarkers for adsorptive GMA. Expert opinion: In UC, adsorptive GMA with Adacolumn (Adacolumn®, JIMRO Co., Ltd. Takasaki, Gunma, Japan) selectively depletes elevated myeloid lineage leukocytes and has a range of beneficial secondary immune effects. Adsorptive GMA is a safe and effective non-pharmacological treatment option for UC. Pilot studies have reported promising results for adsorptive GMA in combination with biological agents, although larger studies are required. Fecal calprotectin concentrations, neutrophil counts in histological samples and/or the neutrophil/lymphocyte ratio in peripheral blood may prove to be useful biomarkers for predicting GMA effectiveness in the future.

https://pubmed.ncbi.nlm.nih.gov/35833363/

https://www.tandfonline.com/doi/epub/10.1080/17474124.2022.2100759?needAccess=true

Iizuka M, Etou T, Sagara S.  World J Gastroenterol 2022; 28(34): 4959-4972 DOI: 10.3748/wjg.v28.i34.4959

For the optimal management of refractory ulcerative colitis (UC), secondary loss of response (LOR) and primary non-response to biologics is a critical issue. This article aimed to summarize the current literature on the use of cytapheresis (CAP) in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations. Further, we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators (IM). Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM. There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM. Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies. Mean remission rates of biologics exposed or unexposed patients were 29.4 % and 44.2%, respectively. Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics. The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69% (mean: 48.0%, median: 42.9%) and 9%-75% (mean: 40.7%, median: 38%), respectively. CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics. Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics, these combination therapies induced clinical remission/response and steroid-free remission in more than 40% of patients with UC refractory to biologics on average. Given the excellent safety profile of CAP, this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics. Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.

https://pubmed.ncbi.nlm.nih.gov/36160647/

https://www.wjgnet.com/1007-9327/full/v28/i34/4959.htm

Hideaki Uchida ¹, Masahiro Kamata ², Shota Egawa ¹, Mayumi Nagata ¹, Saki Fukaya ¹, Kotaro Hayashi ¹, Atsuko Fukuyasu ¹, Takamitsu Tanaka ¹, Takeko Ishikawa ¹, Takamitsu Ohnishi ¹, Kazumitsu Sugiura ³, Yayoi Tada 

J Am Acad Dermatol 2022 Nov;87(5):1181-1184. doi: 10.1016/j.jaad.2022.03.001. 

Granulocyte and monocyte adsorption apheresis (GMA) is an extracorporeal circulation therapy that removes activated granulocytes and monocytes, which can be easily introduced in clinics and hospitals where hemodialysis is performed. Its safety profile  allows for its administration without screening and for its concomitant use with other therapies, indicating that GMA can be a good additional option for GPP treatment. However, the evidence for its efficacy and safety is limited because of the rarity of GPP. Furthermore, its immediate impact on GPP has not been assessed yet. Therefore, we report our real-world experience of 14 patients with GPP treated with GMA after systemic treatment.GMA can be administered with other systemic therapies, including biologics and conventional therapy (objective A). Furthermore, its good safety profile allows GMA administration to a wide range of patients, including elderly patients and those with complications, possible active infection, or malignancy (objectives B and C). Moreover, our study revealed an immediate significant improvement in BT, accompanied by slight decreases in the WBC count and CRP level, indicating that GMA contributes to the rapid suppression of acute inflammation in patients with GPP.

A real-world, single-center experience and the immediate impact of granulocyte and monocyte adsorption apheresis on generalized pustular psoriasis – PubMed (nih.gov)

A real-world, single-center experience and the immediate impact of granulocyte and monocyte adsorption apheresis on generalized pustular psoriasis – Journal of the American Academy of Dermatology (jaad.org)