Scientific corner

Efficacy of cytapheresis in patients with ulcerative colitis showing insufficient or lost response to biologic therapy

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

Scientific corner

Cellular immune response triggered by granulocytoapheresis in ulcerative colitis patients under biological treatment

UEG WEEK VIRTUAL 2021

GMA induces specific immunoregulatory changes in leukocyte’s subpopulations. We confirm the depletion of the
monocytes with proinflammatory phenotype after GMA. Treg and B effector cells shift to a more immunotolerant phenotype. The emergence of subpopulations with the atypical immunofluorescence staining (CXCR3+CRTH2+) related to immature T cells support the immunomodulatory effects of GMA. These findings could help to understand the pathology of UC and to identify targeted immune subpopulations for treatment

P0246 UEG.pdf

Scientific corner

The combined efficacy of adalimumab with GMA method on the treatment of ulcerative colitis and repair of intestinal mucosal lesion

Ailing Song, Hai Jiang, Liang Guo, Shanshan Wu, Am J Transl Res 2021;13(5):5156-5164

Objectives: The study discussed and analyzed the combined efficacy of adalimumab with granulocyte and monocyte adsorption apheresis (GMA) method on patients with ulcerative colitis (UC) and the repair of intestinal mucosal lesion. Methods: 60 UC patients in moderate-to-severe active phase that hospitalized from January 2017 to March 2020 were chosen and randomly classified into observation group (n=30) and control group (n=30). The control-group patients received GMA treatment, and the observation-group patients received combination therapy of GMA and adalimumab. The therapeutic efficacy, laboratory indicators, changes of serum inflammatory factors, and intestinal mucosal barrier impairment in two sets of participants were compared. Results: The comprehensive effective rate of clinical treatment was remarkably higher in observation group than that in control group (P<0.05). CRP and ESR of the two groups in post- treatment were notably lower than those before treatment (P<0.05), while Hb and ALB in post-treatment increased significantly than in pre-intervention (P<0.05); CRP in observation group after treatment was remarkably lower than that in control group (P<0.05), while no significant difference was noticed in ESR, ALB and Hb between the two groups (P>0.05). The serum inflammatory factors in observation group in post-treatment were significantly lower than those in the control group (P<0.05). The scores of PCT, DAO and intestinal mucosa in two sets of participants in post-treatment were dramatically lower than those in pre-treatment (P<0.05), and the scores in observation group after treatment were notably lower than those in the control group (P<0.05). Conclusions: 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/34150104/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205815/pdf/ajtr0013-5156.pdf

Scientific corner

Chronic Antibiotic-Refractory Pouchitis: Management Challenges

Outtier AFerrante M, Clin Exp Gastroenterol. 2021; 14: 277–290. Doi.:10.2147/CEG.S219556

Pouchitis can be suspected based on clinical symptoms and laboratory findings, but should be confirmed with endoscopy and histology. Clear definitions should be used to classify pouchitis into acute versus chronic, and responsive versus dependent versus refractory to antibiotics. Before treatment is started for chronic antibiotic-refractory pouchitis, secondary causes should be ruled out. Also, scoring the disease, taking into account the quality of life of the patient, should guide you in choosing the best treatment option for your patient.

Managing patients with chronic antibiotic-refractory pouchitis remains a challenge for the treating gastroenterologist or abdominal surgeon. Because chronic antibiotic-refractory pouchitis is mainly immune mediated, therapeutic options are similar to the treatment strategies for inflammatory bowel diseases. Treatments with antibiotics, aminosalicylates, steroids, immunomodulators and biologics has been shown to be effective for chronic antibiotic-refractory pouchitis. Also, treatments with AST-120, hyperbaric oxygen therapy, tacrolimus enemas, and granulocyte and monocyte apheresis suggested some efficacy. The available data are weak but suggest that therapeutic options for chronic antibiotic-refractory pouchitis are similar to the treatment strategies for inflammatory bowel diseases. However, randomized controlled trials are warranted to further identify the best treatment options in this patient population.

Chronic Antibiotic-Refractory Pouchitis: Management Challenges | CEG (dovepress.com)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213947/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213947/pdf/ceg-14-277.pdf

Scientific corner

SY4-03 The efficacy of combination therapy of intensive GMA with biologics or a JAK inhibitor for refractory inflammatory bowel disease

Satoshi Tanida

poster at ISFA 2019 pag 56

Background and Aim: A monotherapy with intensive GMA, biologics or a JAK inhibitor are limited in patients with intractable Crohn’s disease (CD) or ulcerative colitis (UC). We retrospectively evaluated the 10- and 52-week efficacy and safety of combination therapy of intensive GMA with biologics or a JAK inhibitor for intractable UC or CD.
Method: A combination of intensive GMA (2 sessions a week, total 10 times) with tofacitinib (TOF) for active UC was performed and that of intensive GMA with ustekinumab (UST) for active CD was done. Results: Of 6 consecutive UC patients receiving a combination therapy of TOF (20 mg daily for 8 weeks as induction therapy and subsequently 10 mg daily) plus intensive GMA for moderately-to-severely active UC and loss of response to corticosteroids, azathioprine, and/ or biologic therapies, 67% (4 cases) displayed clinical remission according to Mayo score and 100% displayed mucosal healing at 10 weeks. A temporary increase in CPK were seen. Of 5 consecutive CD patients receiving a combination therapy of ustekinumab (every 8 weeks) plus intensive GMA for moderately-to-severely active CD and loss of response to corticosteroids, azathioprine, and/or biologic therapies, 75% displayed cumulative steroid-free clinical remission at 10 weeks and did such remission over 52 weeks under subsequent maintenance monotherapy of UST. The mean CDAI at baseline were 257. Its values at 10 and 52 weeks after the combination therapy with UST plus intensive GMA were 48 and 68, respectively. One case showed mucosal healing at 52 weeks according to SES-CD. No adverse events were observed. Conclusions: Combination therapy of intensive GMA with biologics or a JAK inhibitor appeared to be effective and safe for refractory UC or CD.

http://www.atalacia.com/isfa/data/abstract.pdf

Scientific corner

Safety and efficacy of granulocyte/monocyte apheresis in steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics (ART trial): 12-week interim results.

Axel Dignass 1Ayesha Akbar 2Ailsa Hart 2Sreedhar Subramanian 3Gilles Bommelaer 4Daniel C Baumgart 5Jean-Charles Grimaud 6Guillaume Cadiot 7Richard Makins 8Syed Hoque 9Guillaume Bouguen 10Bruno Bonaz 11 , J Crohns Colitis. 2016 Jul;10(7):812-20. 

At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgroup.

https://pubmed.ncbi.nlm.nih.gov/26818659/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955912/pdf/jjw032.pdf

Scientific corner

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/

Scientific corner

Current Treatment Options for Inflammatory Bowel Diseases and Future Perspectives

TARO OSADA*, SUMIO WATANABE*, Juntendo Medical Journal61 (6), 588-596

In recent years, landmark progress has been made in the treatment of patients with inflammatory bowel
diseases (IBD). The anti-tumour necrosis factor (TNF)-α antibody era has shown that mucosal healing is a key
therapeutic goal, and may predict the sustainability of remission or resection-free survival in IBD patients.
Further, the anti-TNF-α antibody infliximab (IFX) became an alternative medication for refractory UC in 2010
under the Japan national health reimbursement scheme. However, to induce remission in steroid-refractory UC,
currently several therapeutic options are available in Japan including cytapheresis, tacrolimus, and anti-TNF-α
biologics, but as yet, there are no guidelines for the sequence and timing of these therapeutic interventions.
Additionally, there are many patients who do not respond, or are intolerant, to anti-TNF-α biologics. Recently,
new strategies like faecal microbiota transplantation and anti-leucocyte infiltration have been tested for induction
and maintenance of remission in IBD patients. This paper provides an overview of the latest treatment options and
future perspectives in IBD therapy

https://www.jstage.jst.go.jp/article/jmj/61/6/61_588/_pdf/-char/en

Contact UsFor more information

Contact Us