Makoto Naganuma ¹, Taku Kobayashi ², Reiko Kunisaki ³, Katsuyoshi Matsuoka ⁴, Shojiro Yamamoto ⁵, Ami Kawamoto ⁶, Daisuke Saito ⁷, Kosaku Nanki ⁸, Kazuyuki Narimatsu ⁹, Hisashi Shiga ¹⁰, Motohiro Esaki ¹¹, Shinichiro Yoshioka ¹², Shingo Kato ¹³, Masayuki Saruta ¹⁴, Shinji Tanaka ¹⁵, Eriko Yasutomi ¹⁶, Kaoru Yokoyama ¹⁷, Kei Moriya ¹⁸, Yoshikazu Tsuzuki ¹⁹, Makoto Ooi ²⁰, Mikihiro Fujiya ²¹, Atsushi Nakazawa ²², Takayuki Abe ²³, Tadakazu Hisamatsu ⁶; Japanese UC Study Group J Gastroenterol. 2023 Dec;58(12):1198-1210. doi: 10.1007/s00535-023-02048-w. 

Background: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC).

Methods: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT.

Results: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization.

Conclusion: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.

Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis – PubMed (nih.gov)

Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis | Journal of Gastroenterology (springer.com)

Nobuhiro Ueno Seisuke Saito Masahiro Sato Yuya Sugiyama doi: 10.21203/rs.3.rs-3037827/v1

Background: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn was given to patients with active Crohn’s disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with active CD remains unclear. Methods: This multicenter retrospective cohort study encompassed patients with CD who underwent GMA in seven independent institutions in Japan from January 2010 to March 2023. All clinical data were obtained from medical records. This study aimed to evaluate the clinical efficacy, safety, and subsequent clinical progression after GMA in patients with CD. Result: This study enrolled 173 patients with active inflammatory bowel disease who underwent GMA with Adacolumn, and among them, 16 patients with CD with mild to moderate disease activity were analyzed. Concomitant medication, including steroids, immunomodulators, and biologics, was used in 93.7% of all cases. The overall remission and response rates were 25.0% and 68.8%, respectively. The response rate between groups concerning the frequency and total GMA sessions revealed no significant difference. Six (37.5%) patients experienced adverse events (AEs). All AEs were related to the trouble in blood access and recovered soon without any sequelae. Regarding the factors associated with response to GMA, the responder group had a significantly longer disease duration (336 vs 44 months, p = 0.036) and exhibited a relatively lower rate of intestinal strictures and a median score of a simple endoscopic score for CD (SES-CD) (9.1 vs 60 %, p = 0.063 and 10 vs 21.5, p = 0.091, respectively). Further, all patients responding to GMA received biologics that were continuously used before and after GMA. Furthermore, 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to anti-tumor necrosis factor-α agent. Conclusion: Therefore, GMA may exhibit heightened effectiveness in patients with moderately active CD without severe endoscopic activity. Moreover, it represents a potential novel therapeutic option for refractory CD, particularly with insufficient response to biologics.

(PDF) The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn’s disease: A multicenter retrospective cohort study (researchgate.net)

Nobuhiro Ueno ¹, Yuya Sugiyama ¹, Yu Kobayashi ¹, Yuki Murakami ¹, Takuya Iwama ², Takahiro Sasaki ¹, Takehito Kunogi ¹, Aki Sakatani ¹, Keitaro Takahashi ¹, Kazuyuki Tanaka ³, Shinya Serikawa ⁴, Katsuyoshi Ando ¹, Shin Kashima ¹, Momotaro Muto ⁵, Yuhei Inaba ², Kentaro Moriichi ¹, Hiroki Tanabe ¹, Toshikatsu Okumura ¹, Mikihiro Fujiya

J Clin Apher.  2023 Jan 13. doi: 10.1002/jca.22040.

Background: Granulocyte and monocyte adsorptive apheresis (GMA) with Adacolumn has been used as a remission induction therapy for patients with active ulcerative colitis (UC). Herein, we investigated the influence of concomitant medications in the remission induction of GMA in patients with active UC. Methods: This multicenter retrospective cohort study included patients with UC underwent GMA in five independent institutions in Japan from January 2011 to July 2021. Factors including concomitant medications associated with clinical remission (CR) were analyzed statistically. Result: A total of 133 patients were included. Seventy-four patients achieved a CR after GMA. The multivariable analysis revealed that concomitant medication with 5-aminosalicylic acid, Mayo endoscopic subscore (MES), and concomitant medication with immunosuppressors (IMs) remained as predictors of CR after GMA. In the subgroup analysis in patients with MES of 2, concomitant medication with IMs was demonstrated as a significant negative factor of CR after GMA (P = .042, OR 0.354). Seventy-four patients who achieved CR after GMA were followed up for 52 weeks. In the multivariable analysis, the maintenance therapy with IMs was demonstrated as a significant positive factor of sustained CR up to 52 weeks (P = .038, OR 2.214). Furthermore, the rate of sustained CR in patients with biologics and IMs was significantly higher than that in patients with biologics only (P = .002). Conclusion: GMA was more effective for patients with active UC that relapsed under treatment without IMs. Furthermore, the addition of IMs should be considered in patients on maintenance therapy with biologics after GMA.

Concomitant pharmacologic medications influence the clinical outcomes of granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis: A multicenter retrospective cohort study – PubMed (nih.gov)

Yoh Ishiguro ¹, Toshihide Ohmori ², Ken Umemura ³, Masahiro Iizuka ⁴ ,Ther Apher Dial 2020 Oct 7.

GMA was an effective treatment for corticosteroid-naïve patients and the efficacy sustained longer in those not receiving immunomodulators during GMA. GMA fulfills the notion that apheresis is to induce disease remission by removing from the body factors known to perpetuate disease. In therapeutic settings, these findings should help better decision making and avoid futile use of medical resources.

https://pubmed.ncbi.nlm.nih.gov/33029920/

Maki Miyakawa, Hiroki Tanaka, Tomoyoshi Shibuya,Taro Osada, Eiji Hosoi Gastroenterol. 2019 156 (6) Suppl.S-666–S-667

Background: Few studies have assessed the safety of granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) undergoing concomitant treatment with multiple immunosuppressant medications. To address this research gap, we investigated adverse effects associated with GMA in patients with IBD treated with multiple immunosuppressants  who  participated  in  the  “Post-marketing  surveillance  study  on  the safety and response of GMA treatment in patients with Crohn’s disease or ulcerative colitis with at least one special situation who received Adacolumn® (PARTICULAR).” Methods: The PARTICULAR study was a retrospective, multicenter cohort study of patients with ulcerative colitis (UC) or Crohn’s disease (CD) who received GMA between November 2013 and March 2017. Patients meeting at least one of the following special situation were enrolled: elderly (<=65 years) or pediatric/adolescent (>=18 years) patients, patients with anemia, or patients undergoing concomitant treatment with multiple immunosuppressants. GMA was performed using Adacolumn® (JIMRO, Takasaki, Japan). Each patient received up to 11 GMA sessions, and all adverse events (AEs) during the study period were recorded. The incidence of AEs was investigated relative to the number and type of immunosuppressants using univariate and multivariate logistic regression analyses. Results: A total of 437 patients (368 UC, 69 CD) from 93 institutions were included. Of these, 140, 169, 101, and 27 patients received none, 1, 2, and >=3 immunosuppressants, respectively. In total, 125 patients received multiple immunosuppressants. Concomitant prednisolone, immunomodulators, anti-tumor necrosis factor agents, and calcineurin inhibitors were administered in 189, 151, 89, and 24 patients, respectively. The incidence of AEs was 11% in all 437 patients and 8%, 12%, 12%, and 26% in patients receiving none, 1, 2, and >=3 immunosuppressants, respectively. In multivariate logistic regression analysis, anemia and concomitant immunosuppressants were independently associated with the incidence of AEs. Particularly, a higher number of concomitant immunosuppressants showed an increasing trend with odds ratios related to AEs. In contrast, concomitant corticosteroids were associated with a reduced risk of AEs. Nausea/vomiting and headache were the most common AEs in patients on multiple immunosuppressant medications (5.6% and 3.2%, respectively). Conclusions: Concomitant treatment with immunosuppressants was independently associated with the incidence of AEs such as nausea/vomiting and headache in patients with IBD receiving GMA. As the number of concomitant immunosuppressants increased, the incidence of AEs also increased. However, our data also suggest that GMA is safe in patients with IBD receiving prednisolone.

https://www.gastrojournal.org/action/doSearch?text1=granulocyte+and+monocyte+apheresis+&field1=AllField&AfterYear=2018&BeforeYear=2021&pageSize=50&startPage=&SeriesKey=ygast

Takahiro Shimoyama ¹, Takayuki Yamamoto ², Satoru Umegae ¹, Koichi Matsumoto ¹ , BMC Gastroenterol. 2018 Aug 1;18(1):120.

Our findings indicate that FC is a relevant biomarker, which is convenient to measure for assessing endoscopic activity and predicting relapse in patients who achieve remission following a course of GMA therapy.

https://pubmed.ncbi.nlm.nih.gov/30068300/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090982/pdf/12876_2018_Article_853.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