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

Tomoyoshi Shibuya ¹, Keiichi Haga ¹, Masato Kamei ¹, Koki Okahara ¹, Shoko Ito ¹, Masahito Takahashi ¹, Osamu Nomura ¹, Takashi Murakami ¹, Masae Makino ¹, Tomohiro Kodani ¹, Dai Ishikawa ¹, Naoto Sakamoto ¹, Taro Osada ¹, Tatsuo Ogihara ¹, Sumio Watanabe ¹, Akihito Nagahara ¹ , Intest Res. 2018 Jul;16(3):484-488.

Our experience indicates that GMA, as a non-drug therapeutic intervention with a favorable safety profile, plus tacrolimus might be a relevant treatment option for patients with active IBD during pregnancy. A future study of a large cohort of pregnant patients should strengthen our findings.

https://pubmed.ncbi.nlm.nih.gov/30090048/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077305/pdf/ir-16-484.pdf

Hiroki Tanaka, Satoshi Motoya, Tomoyoshi Shibuya, Satoshi Tanida, Seiichiro Kokuma, Eiji Hosoi Gastroenterology 2018 154 (6) Suppl.S-996–S-997

Background: There are few studies on the usefulness of granulocyte and monocyte adsorptive apheresis (GMA) in elderly patients with inflammatory bowel disease (IBD). We investigated the safety and effectiveness of GMA in elderly patients who participated in the Post-marketing Surveillance Study of GMA Using Adacolumn® for Patients with Inflammatory Bowel Disease Who Have Special Situations (PARTICULAR). Methods: The PARTICULAR study is a retrospective, multicenter cohort study that included patients with ulcerative colitis (UC) or Crohn’s disease (CD) who received GMA between November 2013 and March 2017. Patients with at least one special situation, including elderly patients, patients with anemia, and patients undergoing concomitant treatment with multiple immunosuppressants (IMs) were enrolled. Patients aged # 64 years were excluded from this study. GMA was performed using Adacolumn® (JIMRO, Takasaki, Japan). Each patient received up to a maximum of 11 GMA sessions. The safety of GMA was assessed in all patients. The effectiveness of GMA was assessed in patients with UC with a partial UC disease activity index (pUC-DAI) score of $ 3. Remission was defined as a pUC-DAI score of # 2. Patients receiving concomitant treatment with infliximab, adalimumab, or calcineurin inhibitors were excluded from the effectiveness assessment. The incidence of adverse events (AEs) and remission rates were compared between elderly patients with and without any special situation using univariate and multivariate logistic regression analysis. Results: A total of 125 elderly patients (118 UC, 7 CD) from 93 institutions were included. The median age was 73.2 years. Fifty-six patients did not have any special situation, and 69 had at least one or more special situations. The incidence of AEs was 11.2% in all patients. The incidence of AEs was significantly lower in elderly patients without any special situation (3.6%) than in those with at least one or more special situations (17.4%) (Figure 1A). AEs significantly occurred in elderly patients with anemia (21.9%) and on multiple concomitant IMs (23.8%) compared to those without any special situation (3.6%). Anemia and multiple concomitant IMs were identified as independent predictors for a higher incidence of AEs (Table 1). The effectiveness of GMA was assessed in 92 patients with UC. The remission rate was 48.9%. No difference was observed in the remission rate between elderly patients without any special situation (52.2%) and those with at least one or more special situations (45.7%) (Figure 1B). Conclusions: A low incidence of AEs (3.6%) was found in elderly IBD patients receiving GMA without any special situation. Remission was achieved by GMA in 48.6% of the elderly UC patients. Care should be taken when using GMA in elderly IBD patients with anemia or on multiple concomitant IMs

Eugeni Domènech ¹, Julián Panés ², Joaquín Hinojosa ³, Vito Annese ⁴, Fernando Magro ⁵, Giacomo Carlo Sturniolo ⁶, Fabrizio Bossa ⁷, Francisco Fernández ⁸, Benito González-Conde ⁹, Valle García-Sánchez ¹⁰, Axel Dignass ¹¹, José Manuel Herrera ¹², José Luis Cabriada ¹³, Jordi Guardiola ¹⁴, Maurizio Vecchi ¹⁵, Francisco Portela ¹⁶, Daniel Ginard ¹⁷, J Crohns Colitis. 2018 May 25;12(6):687-694.

In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

https://pubmed.ncbi.nlm.nih.gov/29490024/

Yoko Yokoyama ¹, Koji Kamikozuru ², Kenji Watanabe ², Shiro Nakamura ² , Cytokine. 2018 Mar;103:25-28.

To our best knowledge, this is the first report of adding a non-drug GMA to restore the efficacy of infliximab. The outcomes, albeit in three cases, are relevant in therapeutic settings and should inspire further studies in a larger number of patients.

https://pubmed.ncbi.nlm.nih.gov/29291447/

Iago Rodríguez-Lago ¹, José Luis Cabriada ² , Cytokine. 2018 Apr;104:29.

https://pubmed.ncbi.nlm.nih.gov/29414323/

Cabriada, J.L., Rodríguez-Lago, I.

Enfermedad Inflamatoria Intestinal 20017 (16) 2, 62-69 DOI: 10.1016/j.eii.2016.12.001 

Granulocyte apheresis is a procedure that allows the removal of different activated leukocyte populations and it also modifies some circulating inflammatory mediators. These effects, along with its immunomodulatory potential, make it an attractive therapeutic option in inflammatory bowel disease. Previous studies with this technique have had significant limitations, but recent data is emerging about the ideal clinical setting in which granulocyte apheresis should be indicated. Most of the evidence supports its use in conditions that are dependent or refractory to corticosteroids, especially when treatments with immunomodulators or biologics has failed and when it is necessary to reduce or avoid the use of systemic corticosteroids. Its excellent safety profile gives it a role in cases of comorbidity or risk in the use of immunosuppressive drugs or in paediatric patients. In this review, we provide an update on the role of granulocyte apheresis in inflammatory bowel disease.

https://www.elsevier.es/es-revista-enfermedad-inflamatoria-intestinal-al-dia-220-articulo-granulocitoaferesis-2017-puesta-al-dia-S1696780116300999

Kazuhiro Watanabe ¹, Yoshihito Uchida ¹, Kayoko Sugawara ¹, Kayoko Naiki ¹, Mie Inao ¹, Nobuaki Nakayama ¹, Satoshi Mochida ² , J Gastroenterol 2017 Jul;52(7):830-837.

Sequential therapy combining glucocorticoid infusion and GMA was useful for attenuating liver injuries in patients with severe alcoholic hepatitis by preventing rebound increases in inflammatory reactions after discontinuation of glucocorticoid infusions, except in patients with bacterial infections and/or multiple organ failure.

https://pubmed.ncbi.nlm.nih.gov/27858246/

Iago Rodríguez-Lago ¹, Laura Gómez-Irwin ², Encarnación Fernández ³, Rebeca Higuera ⁴, José Luis Cabriada ¹ , Ther Apher Dial. 2017 Feb;21(1):26-30.

Adjuvant treatment with leukapheresis in patients with inadequate response to anti-TNF treatment showed some beneficial effect, although of limited duration, in patients with ulcerative colitis.

https://pubmed.ncbi.nlm.nih.gov/28078747/

Kotaro Kuwaki ¹, Keiichi Mitsuyama ², Hayato Kaida ³, Hidetoshi Takedatsu ¹, Shinichiro Yoshioka ¹, Hiroshi Yamasaki ¹, Ryosuke Yamauchi ¹, Shuhei Fukunaga ¹, Toshi Abe ³, Osamu Tsuruta ¹, Takuji Torimura ¹ , Cytotherapy. 2016 Feb;18(2):291-9.

The longitudinal changes in FDG-PET uptakes are of potential clinical interest for assessing the regional and global bowel disease activity in CD patients undergoing GMA therapy.

https://pubmed.ncbi.nlm.nih.gov/26700210/