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An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis

Francesca Ferretti 1Rosanna Cannatelli 1Maria Camilla Monico 1Giovanni Maconi 1Sandro 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/

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Complete Resolution of Mucosal Neutrophils Associates With Improved Long-Term Clinical Outcomes of Patients With Ulcerative Colitis

Rish K Pai 1Douglas J Hartman 2Claudia Ramos Rivers 3Miguel Regueiro 4Marc Schwartz 3David G Binion 3Reetesh K Pai Clin Gastroenterol Hepatol 2020 Oct;18(11):2510-2517.e5. doi: 10.1016/j.cgh.2019.12.011. Epub 2019 Dec 14.

Background & aims: We investigated correlations between histologic features of the colonic mucosa in patients with ulcerative colitis (UC) and clinical outcomes during a 3-year follow-up period. Methods: We obtained baseline biopsies from all colorectal segments (n = 889) from 281 patients with UC enrolled in a prospective study at a single center from 2009 through 2013. Biopsies were assessed in a blinded manner using validated histologic scoring systems (the Geboes score, Nancy histopathologic index, and Robarts histopathologic index). Clinical, endoscopic, and histologic data were collected and tested for correlations with systemic corticosteroid use, hospitalization, and colectomy within 3 years of the index colonoscopy. Results: We found histologic evidence of UC activity (Geboes score ≥ 2B.1) in biopsies from 182 patients (65%) and endoscopic evidence of UC activity in 149 patients (53%) (substantial agreement, κ = 0.60). Histologic features of UC activity were associated with increased rates of systemic corticosteroid use, colectomy, and hospitalization in the entire cohort (P < .05 for all) and associated with increased rates of systemic corticosteroid use in an analysis limited to patients in endoscopic remission (P < .001). In patients in endoscopic remission, only histologic activity was independently associated with use of systemic corticosteroids (multivariate odds ratio, 6.34; 95% CI, 2.20-18.28; P = .001). Similar results were seen when the entire cohort was analyzed. Compared with patients without histologic evidence of UC activity, patients with only a small number of mucosal neutrophils still had higher rates of systemic corticosteroid use (P < .001). Conclusions: Histologic evidence of UC activity, including small numbers of neutrophils in the colonic mucosa, is the only factor independently associated with use of systemic corticosteroids. Complete resolution of neutrophil-associated inflammation should be a target for treatment of UC.

https://pubmed.ncbi.nlm.nih.gov/31843598/

https://www.cghjournal.org/article/S1542-3565(19)31438-7/fulltext

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Pyoderma gangrenosum with primary sclerosing cholangitis-associated colitis successfully treated with concomitant granulocyte and monocyte adsorption apheresis with corticosteroids

Munenori Kawai 1Chiharu Kawanami 2Akihisa Fukuda 3Hiroshi Seno 3 Clin J Gastroenterol. 2021 Jun 8. doi: 10.1007/s12328-021-01460-0. Online ahead of print

Together with previous reports, concomitant GMA therapy with corticosteroids may be an effective treatment for PG.

https://pubmed.ncbi.nlm.nih.gov/34101129/

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Adsorptive Granulocyte and Monocyte Apheresis Is Effective in Ulcerative Colitis Patients Both with and without Concomitant Prednisolone

Keiji Matsuda 1 2Kohei Ohno 1Yuka Okada 1Takahiro Yagi 1Mitsuo Tsukamoto 1Yoshihisa Fukushima 1Atsushi Horiuchi 1Ryu Shimada 1 2Tsuyoshi Ozawa 1 2Tamuro Hayama 1 2Takeshi Tsuchiya 1 2Junko Tamura 1Hisae Iinuma 1Keijiro Nozawa 1 2Hitoshi Aoyagi 2 3Akari Isono 2 3Koichiro Abe 2 3Shinya Kodashima 2 3Takatsugu Yamamoto 2 3Yoshitaka Kawasaki 4Yoshifuru Tamura 4Yuko Sasajima 5Fukuo Kondo 5Yojiro Hashiguchi 1 2 , Inflamm Intest Dis, 2020 Feb;5(1):36-41.

The effect of GMA with concomitant PSL (Prednisolone) and that of GMA without PSL were not different, and GMA was effective irrespective of PSL administration. The present study showed that GMA had efficacy and led many UC patients treated by PSL to be steroid free with no safety concern in the real world, although there is the possibility of recruitment bias due to the retrospective nature of the study.

https://pubmed.ncbi.nlm.nih.gov/32232053/

https://www.karger.com/Article/Pdf/505484

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Pyoderma Gangrenosum with Ulcerative Colitis Successfully Treated by the Combination of Granulocyte and Monocyte Adsorption Apheresis and Corticosteroids

Masashi Ohno 1Shigeki KoyamaMariko OharaKazumi ShimamotoYu KobayashiFumiyasu NakamuraKazuki MitsuruAkira Andoh, Intern Med. 2016;55(1):25-30.

 These results suggest that a combination of GMA and corticosteroids might be recommendable to induce the remission of serious PG complicated with UC.

https://pubmed.ncbi.nlm.nih.gov/26726081/

https://www.jstage.jst.go.jp/article/internalmedicine/55/1/55_55.5422/_article

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Efficacy and usefulness of new single-needle Intensive granulocyte and monocyte adsorptive apheresis in active ulcerative colitis patients without corticosteroids and biologics

Keiji Shimazu 1Takumi Fukuchi 2Insung Kim 3Yuki Noguchi 3Megumi Iwata 1Shintaro Koyama 2 4Satoshi Ubukata 2Atsuo Tanaka 1 , Ther Apher Dial 2016 Aug;20(4):383-9.

Intensive granulocyte and monocyte adsorptive apheresis (GMA) twice weekly is effective and safe for patients with active ulcerative colitis (UC), but the requirement for maintaining two blood access routes is problematic. Here we compared the efficacy and safety of one-route blood access intensive GMA using a single-needle (SN) and conventional two-route blood access intensive GMA using a double-needle (DN) in patients with active UC not undergoing corticosteroid therapy. Among 80 active UC patients, 38 patients received SN intensive GMA and 42 patients received DN intensive GMA. The clinical remission ratio and mucosal healing ratio at 6 weeks, and the cumulative non-relapse ratio at 52 weeks did not differ significantly between groups. In addition, no serious or mild adverse effects were observed in SN intensive GMA. SN intensive GMA may be an adequate and novel therapeutic option for active UC as an alternative therapy before using corticosteroids.

https://pubmed.ncbi.nlm.nih.gov/27523079/

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Efficacy and safety of granulocyte and monocyte adsorption apheresis for ulcerative colitis: A meta-analysis.

Takuya Yoshino 1Hiroshi Nakase 2Naoki Minami 3Satoshi Yamada 3Minoru Matsuura 3Shujiro Yazumi 4Tsutomu Chiba 3 , Dig Liver Dis. 2014 Mar;46(3):219-26.

Our meta-analysis reveals that intensive granulocyte and monocyte adsorption apheresis is a safe and effective treatment with higher rates of clinical remission and response for ulcerative colitis compared with corticosteroids.

https://pubmed.ncbi.nlm.nih.gov/24268950/

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Steroid-sparing strategies in the management of ulcerative colitis: Efficacy of leukocytapheresis.

Manabu ShirakiTakayuki Yamamoto , World J Gastroenterol. 2012 Nov 7;18(41):5833-8.

Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonpharmacologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is efficacious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treatment of active UC; however, long-term, high doses of corticosteroids usually produce predictable and potentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be minimized. This may be of great benefit to patients because severe side effects of steroids seriously impair health-related quality of life. In this article, we reviewed current evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the management of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-naïve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid-sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, the available data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.

https://pubmed.ncbi.nlm.nih.gov/23139598/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491589/pdf/WJG-18-5833.pdf

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Granulocyte and monocyte adsorption apheresis for generalized pustular psoriasis

Ryoko Shukuya 1Toshio HasegawaYusuke NiwaKeiko OkumaShigaku Ikeda , J Dermatol. 2011 Dec;38(12):1130-4.

Granulocyte and monocyte adsorption apheresis (GCAP) is an extracorporeal circulation therapy that removes activated granulocytes and monocytes. GCAP was initially approved for the treatment of ulcerative colitis, which is attributed to activated granulocytes and macrophages that infiltrate the target tissues. Generalized pustular psoriasis (GPP) is also supposed to be caused by activated neutrophils. In this study, we treated two patients with refractory GPP by using GCAP. Patient 1, a 68-year-old woman who had liver cirrhosis, underwent seven GCAP sessions. Patient 2, a 26-year-old woman who had systemic lupus erythematosus and had been treated with systemic corticosteroids, underwent eight GCAP sessions. In both patients, GCAP resulted in an immediate improvement in skin lesions and fever reduction, without any adverse effects. We suggest that GCAP is an effective therapy for refractory GPP.

https://pubmed.ncbi.nlm.nih.gov/22007872/

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Cytapheresis in patients with severe ulcerative colitis after failure of intravenous corticosteroid: a long-term retrospective cohort study

Ken Fukunaga 1Kazuko NagaseTakeshi KusakaNobuyuki HidaYoshio OhdaKoji YoshidaKatsuyuki TozawaKoji KamikozuruM IimuroShiro NakamuraHiroto MiwaTakayuki Matsumoto, Gut Liver. 2009 Mar;3(1):41-7. doi: 10.5009/gnl.2009.3.1.41

This study suggest that CAP is an effective therapy in patients who are refractory to conventional medications including iv corticosteroid. Increased remission rates should be expected in refractory patients with moderately severe UC.

https://pubmed.ncbi.nlm.nih.gov/20479900/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871568/pdf/gnl-3-41.pdf

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