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/

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

Tomoyoshi Shibuya,Keiichi Haga,Michio Saeki,Mayuko Haraikawa,Hitoshi Tsuchihashi,Koki Okahara,Osamu Nomura,Hirofumi Fukushima,Takashi Murakami Dai Ishikawa,Shigaku Ikeda,Akihito Nagahara

J Clin Apher.  2020 Sep;35(5):488-492. doi: 10.1002/jca.21821. Epub 2020 Aug 7.

Pyoderma gangrenosum (PG) is an extra-intestinal skin lesion in inflammatory bowel disease (IBD) as is erythema nodosum. Vedolizumab (VED) is a monoclonal antibody that targets α4β7 integrin and has an intestinal selective mechanism. Despite good therapeutic effects on colitis, the effect on extra-intestinal manifestations (EIMs) remains unclear. Here we report a case of ulcerative colitis complicated by PG during treatment with VED, which was successfully treated with prednisolone in combination with adsorptive granulocyte and monocyte apheresis (GMA). The patient was a 50-year-old woman with a past medical history of extensive ulcerative colitis managed by golimumab (GLM). She developed flare symptoms due to loss of response to GLM, and treatment was switched to VED. Her gastrointestinal symptoms were improved with VED treatment with less frequent bowel movements. However, infiltrative erythema with pain appeared on the right lower leg and right knee, and expanded and gradually ulcerated. Her skin lesions were treated with corticosteroid, but showed poor improvement. Therefore, granulocyte and monocyte apheresis (GMA) treatment was administered in combination with prednisolone. After 3 months, the ulcer gradually improved, and at the time of this writing, the eruptions were nearly replaced by epithelial tissue. This case study showed that patients with UC and EIMS may respond well to combination therapy of VED and GMA. GMA has a very favorable safety profile. On the other hand, the causal connection between VED and PG is still unclear. We believe that a combination therapy involving VED and GMA in IBD patients with EIMs warrants consideration.

https://pubmed.ncbi.nlm.nih.gov/32767842/

Iago Rodríguez-Lago ^1 2, José M Benítez ^3 4, Laura Sempere ⁵, Esteban Sáez-González ⁶, Manuel Barreiro-de Acosta ⁷, Jone O de Zárate ⁸, José L Cabriada ^1 2 , J Clin Apher 2019 Dec;34(6):680-685.

Objectives: To assess the effectiveness and safety of combining granulocyte-monocyte apheresis (GMA) and vedolizumab (VDZ) in patients with refractory ulcerative colitis (UC). Methods: This retrospective, multicentre pilot study included all UC patients receiving both GMA and VDZ. We recorded data on GMA sessions, demographic characteristics, and clinical response. Effectiveness was assessed 1 and 6 months after finishing the GMA using the partial Mayo score, C-reactive protein, and fecal calprotectin levels. Data were also compiled on VDZ intensification, use of new immunomodulators and colectomy during follow-up. Results: Eight patients were included (mean age 46 years; 63% female; mean disease duration, 132 months; 50% E3). GMA was started after a loss of response to VDZ in all cases (25% primary nonresponse and 75% secondary loss of response). All had previously received anti-TNF agents. VDZ was prescribed as the second-, third-, or fourth-line biologic in 37%, 50%, and 13% of cases, respectively. Patients had a mean baseline partial Mayo score of 7.5 (SD 2.1) and received a median of 15 GMA sessions (range 5-38). After a median follow-up of 7.5 months (IQR 5-12), partial Mayo score decreased after 1 and 6 months (P = .01 and .06, respectively). Three patients (38%) achieved steroid-free clinical remission and five (63%) withdrew VDZ. Colectomy rate was 38%. No adverse events were observed during the combination therapy. Conclusions: This small case series suggests that combining GMA with VDZ could be a treatment option in selected cases of UC with an inadequate response to this biologic agent.

https://pubmed.ncbi.nlm.nih.gov/31518013/

Esteban Sáez-González ¹, Mariam Aguas ², José M Huguet ³, Pilar Nos ⁴, Belén Beltrán ² , Dig Liver Dis. 2018 Apr;50(4):415-417.

We have reported the first case of using GMA in combination with vedolizumab in a patient with active, steroid-dependent UC with an inadequate response to vedolizumab and previous biologic failure to adalimumab and infliximab, achieving remission in the follow-up. It is believed that the primary consequence of GMA therapy is a selective depletion of certain subsets of myeloid leucocytes, the most relevant of which could be the CD14+ CD16+ DR++phenotype, also known as the proinflammatory monocytes.This selective depletion of circulating leucocytes could enhance the reduction of gut trafficking of leucocytes induced by vedolizumab and modify the concentration of proinflammatory cytokines. In this clinical context, GMA therapy could be a safe, on pharmacological treatment that could help to reduce the inflammatory load, thereby enhancing the effect of biologic drugs.

https://pubmed.ncbi.nlm.nih.gov/29397323/

https://www.dldjournalonline.com/article/S1590-8658(18)30138-5/fulltext