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)

Kazunori Adachi ¹, Tomoya Sugiyama ², Yoshiharu Yamaguchi ², Yasuhiro Tamura ², Shinya Izawa ², Masahide Ebi ², Yasushi Funaki ², Naotaka Ogasawara ², Makoto Sasaki ², Kunio Kasugai 

Clin J Gastroenterol. 2023 Feb;16(1):43-47. doi: 10.1007/s12328-022-01716-3. 

A 46-year-old man, receiving continuous steroid therapy for refractory ulcerative colitis with an insufficient response to anti-tumor necrosis factor-α therapy, presented with left buttock pain. He was diagnosed with steroidal left femoral head necrosis, and total proctocolectomy with permanent ileostomy was performed. At 6 months postoperatively, the patient developed general fatigue, abdominal pain, and severe ileostomy diarrhea. Computed tomography revealed continuous intestinal edema from the descending duodenal leg to the upper jejunum. Gastrointestinal endoscopy revealed deep ulcers, coarse mucosa, and duodenal erosion. Based on clinical progress, findings, and pathology, the patient was diagnosed with ulcerative colitis-related postoperative enteritis. Although 5-aminosalicylic acid treatment was initiated, his symptoms persisted, bloody diarrhea from colostomy was observed. Subsequently, granulocyte and monocyte apheresis treatment was added. Symptoms and endoscopic findings improved with granulocyte and monocyte apheresis. Azathioprine was introduced as maintenance therapy, and no sign of recurrence was observed. Although ulcerative colitis-related postoperative enteritis has no definitive treatment, granulocyte and monocyte apheresis may be considered for initial treatment.

A case of ulcerative colitis-related postoperative enteritis treated with granulocyte and monocyte apheresis – PubMed (nih.gov)

Laura Gnesotto ¹, Guido Mioso ¹, Mauro 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/

Farah Yasmin ¹, Hala Najeeb ¹, Unaiza Naeem ¹, Abdul Moeed ¹, Thoyaja Koritala ², Salim Surani ^3 4

World J Clin Cases  2022 Jul 26;10(21):7195-7208. doi: 10.12998/wjcc.v10.i21.7195.

Inflammatory Bowel Disease (IBD) is a hallmark of leukocyte infiltration, followed by the release of cytokines and interleukins. Disease progression to Ulcerative Colitis (UC) or Crohn’s Disease (CD) remained largely incurable. The genetic and environmental factors disrupt enteral bacteria in the gut, which hampers the intestinal repairing capability of damaged mucosa. Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor (TNF)-α. New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response. This review discusses the non-pharmacologic selective granulocyte-monocyte-apheresis (GMA) and leukocytapheresis (LCAP) that have been proposed as treatment modalities that reduce mortality. GMA, an extracorporeal vein-to-vein technique, presents a strong safety profile case for its use as a viable therapeutic option compared to GMA’s conventional medication safety profile. GMA reported minimal to no side effects in the pediatric population and pregnant women. Numerous studies report the efficacious nature of GMA in UC patients, whereas data on CD patients is insufficient. Its benefits outweigh the risks and are emerging as a favored non-pharmacological treatment option. On the contrary, LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release. It has been deemed more efficacious than conventional drug treatments, the former causing better disease remission, and maintenance. Patients with UC/CD secondary to complications have responded well to the treatment. Side effects of the procedure have remained mild to moderate, and there is little evidence of any severe adverse event occurring in most age groups. LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD. The review will discuss the role of GMA and LCAP.

https://pubmed.ncbi.nlm.nih.gov/36158031/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353887/

Mariko Seishima ^1 2, Kento Fujii ³, Yoko Mizutani ³ Am J Clin Dermatol 2022 Jun 15. doi: 10.1007/s40257-022-00698-9.

Generalized pustular psoriasis (GPP) is a rare, severe neutrophilic skin disease characterized by sudden widespread eruption of sterile pustules with or without systemic symptoms. GPP may be life threatening in cases with severe complications such as cardiovascular failure, acute respiratory distress syndrome, and serious infections. Impetigo herpetiformis (IH) is a GPP that is induced and exacerbated by pregnancy and occurs most frequently during the last trimester. IH may result in poor or fatal neonatal outcomes, including placental insufficiency, fetal abnormalities, stillbirth, and early neonatal death. Most patients have prompt remission in the postpartum period; however, earlier appearance and more severe symptoms are observed during subsequent pregnancies. Appropriate treatment and close monitoring of the mother and fetus are vital for the management of patients with IH. Particular attention is required for the management of patients with IH to avoid an influence on the fetus. However, data regarding treatments for GPP in pregnant women are sparse. Over the last decade, many patients with IH have been treated with cyclosporine, corticosteroids, tumor necrosis factor-α inhibitors, interleukin (IL)-17 and IL-12/23 inhibitors, and granulocyte and monocyte adsorption apheresis (GMA). GMA may be an important option for patients with IH as it is presently one of the safest available therapeutic options, but there have been no reports to fully confirm its safety in pregnant patients with GPP. Alternatively, based on recent advances in the understanding of the role of the IL-36 axis in the pathogenesis of GPP, biologic agents that target the IL-36 pathway may demonstrate promising efficacy in IH.

Generalized Pustular Psoriasis in Pregnancy: Current and Future Treatments – PubMed (nih.gov)

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

Francesca Ferretti ¹, Rosanna Cannatelli ¹, Maria Camilla Monico ¹, Giovanni Maconi ¹, Sandro Ardizzone 

J Clin Med  2022 Apr 20;11(9):2302. doi: 10.3390/jcm11092302.

The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients. They also presented other non-Pharmacological Therapies for UC including probiotics, cytapheresis and fecal transplantation.

https://pubmed.ncbi.nlm.nih.gov/35566428/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104748/

Francesca Ferretti ^*, Rosanna Cannatelli, Maria Camilla Monico, Giovanni Maconi and Sandro Ardizzone J. Clin. Med. 2022, 11(9), 2302; 

The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients.

An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis – PubMed (nih.gov)

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

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)

Tomoyoshi Shibuya,Osamu Nomura,Kei Nomura,Mayuko Haraikawa,Keiichi Haga,Dai Ishikawa,Taro Osada,Ken Yamaji,Shigaku Ikeda,Akihito Nagahara

Ther Apher Dial 2022 Mar 5. doi: 10.1111/1744-9987.13823. Online ahead of print.

Introduction: In recent years, the prevalence of inflammatory bowel diseases has been increasing in Japan due to the westernization of lifestyles. Many patients have been reported to have extra-intestinal manifestations (EIMs) at least once. Skin lesions occur with a high degree of frequency among EIMs, with erythema nodosum (EN) and pyoderma gangrenosum (PG) the main complications. Cytapheresis is again attracting attention as a treatment with few side effects. Methods: We investigated the therapeutic effect of cytapheresis on ulcerative colitis (UC) and cutaneous EIMs. Between 2008 and 2021, 240 patients with active UC had induction therapy by cytapheresis at our hospital. Results: Remission and response rates were 50.0% and 67.5%, respectively. Apheresis was performed on seven patients with PG and five patients with EN with a good response. Serious adverse events were not observed. Conclusion: This retrospective assessment of efficacy showed that EN and PG responded favorably to cytapheresis.

https://pubmed.ncbi.nlm.nih.gov/35247233/