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)

Ayumi Ito ¹, Shun Murasugi ¹, Maria Yonezawa ¹, Teppei Omori ¹, Shinichi Nakamura ¹, Katsutoshi Tokushige ¹

J Clin Apher. 2024 Feb;39(1):e22099. doi: 10.1002/jca.22099. Epub 2023 Nov 21.

Background and aims: Primary sclerosing cholangitis has a poor prognosis and can be accompanied by ulcerative colitis. Infection control is essential, so immunosuppressive drugs should ideally be preferably. Granulocyte and monocyte adsorptive apheresis does not suppress the immune system and is used to treat ulcerative colitis. Therefore, this study investigated the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis and ulcerative colitis.

Methods: We retrospectively evaluated data from patients with primary sclerosing cholangitis with ulcerative colitis who visited our hospital from April 2000 to December 2022 and underwent granulocyte and monocyte adsorptive apheresis (n = 10, number of treatment cycles = 15). Study endpoints were remission induction rate and safety, assessed as changes in liver functions and adverse events. Results: Seven of the 10 patients were male. The median (min-max) age was 23 (18-77) years. The most common disease type was right-dominant pancolitis. Remission occurred after 86.6% of cycles (13/15). Serum alkaline phosphatase and Aspartate transaminase were significantly lower after treatment (P = .0124, P = .002), and no negative effects on liver function were seen. The only adverse events were headache (n = 1) and decreased blood pressure (n = 1).Conclusions: Granulocyte and monocyte adsorptive apheresis has high efficacy for intestinal lesions and improves alkaline phosphatase and aspartate transaminase levels (high levels are a poor prognosis factor). It appears to be a treatment option in patients with primary sclerosing cholangitis associated with ulcerative colitis.

Shun Murasugi, Maria Yonezawa, Teppei Omori, Shinichi Nakamura, Katsutoshi Tokushige . J Clin Apher. 2024; 39(1):e22099. doi:10.1002/jca.22099

Background and Aims
Primary sclerosing cholangitis has a poor prognosis and can be accompanied by ulcerative colitis. Infection control is essential, so immunosuppressive drugs should ideally be preferably. Granulocyte and monocyte adsorptive apheresis does not suppress the immune system and is used to treat ulcerative colitis. Therefore, this study investigated the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis and ulcerative colitis.

Methods
We retrospectively evaluated data from patients with primary sclerosing cholangitis with ulcerative colitis who visited our hospital from April 2000 to December 2022 and underwent granulocyte and monocyte adsorptive apheresis (n = 10, number of treatment cycles = 15). Study endpoints were remission induction rate and safety, assessed as changes in liver functions and adverse events.

Results
Seven of the 10 patients were male. The median (min-max) age was 23 (18-77) years. The most common disease type was right-dominant pancolitis. Remission occurred after 86.6% of cycles (13/15). Serum alkaline phosphatase and Aspartate transaminase were significantly lower after treatment (P = .0124, P = .002), and no negative effects on liver function were seen. The only adverse events were headache (n = 1) and decreased blood pressure (n = 1).

Conclusions
Granulocyte and monocyte adsorptive apheresis has high efficacy for intestinal lesions and improves alkaline phosphatase and aspartate transaminase levels (high levels are a poor prognosis factor). It appears to be a treatment option in patients with primary sclerosing cholangitis associated with ulcerative colitis.

I. Rodríguez-Lago1, F. Cañete2, E. Guerra3, C. Herrera de Guise4, E. Iglesias-Flores5, E. Leo-Carnerero6, Y. Zabana7, M. Barreiro de Acosta8, D. Ginard Vicens9, J.L. Cabriada Nuño1

UEG journal 2023 SUPPLEMENT ABSTRACT UEG Week 2023 Poster Presentations 15 October 2023 page 1067

Introduction: Granulocyte–monocyte apheresis (GMA) selectively removes activated leukocytes and immune mediators, and it has shown to be safe and effective in treating ulcerative colitis (UC). Previous reports
have also described its combination with biologics.
Aims & Methods: The aim of our study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. A retrospective, multicentre study was performed in 7 IBD Units, including all patients with refractory UC who received combined plus GMA and TOFA. The number of GMA sessions, its frequency, filtered blood volume and length of each
session were compiled, along with the clinical data. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, CRP and faecal calprotectin. Data regarding TOFA intensification, need for new immunomodulators/biologics and colectomy were also compiled. Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results: Twelve patients with UC were included (median 46 years [IQR, 37-58]; 67% female; 67% E3; 75% non-smokers). Patients were receiving TOFA10 mg bid (75%), 5 mg bid (16%), or 15 mg bid (8%), with 33% receiving
steroids at baseline. All patients had prior exposure to anti-TNF agents, 42% to vedolizumab and 8% ustekinumab. Median baseline Mayo score was 7 (IQR, 5-7), median CRP of 11 mg/L (IQR, 5-32) and faecal calprotectin 800 mg/kg (IQ, 715-2,094). GMA was started mostly after PNR (73%), and the median number of GMA sessions was 11 (IQR, 3-20) and 50% received maintenance GMA. Partial Mayo score significantly decreased 1 month after the last GMA session (p=0.027). Four patients (36%) were switched to a new therapy and no patient required colectomy during follow-up. All patients under steroids at baseline were able to stop them. No patient reported adverse events related to the combination therapy.

Conclusion: Combination of GMA with TOFA can be an effective and safe therapy in selected cases of UC after PNR or LOR to this drug.

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)

Elena Céspedes Martínez, Virginia Robles Alonso, Claudia Herrera-De Guise, Luis Mayorga, Francesc Casellas, María Roca-Herrera, Natalia Borruel, Rev Esp Enferm Dig 2023;115(10):567-573

Introduction: immune checkpoint inhibitors (ICI) are increasingly used to treat several types of cancer. These drugs lead to a wide range of toxicities. Immune-related gastrointestinal adverse events are common and potentially severe. In this manuscript, we recount the real clinical experience in a tertiary center. Methods: a retrospective and observational study was conducted in adult patients under ICI treatment. Included patients had been referred to the Gastrointestinal Service of Hospital Universitario Vall d’Hebron for evaluation of severe toxicities, from January 2017 to January 2020, for whom the clinical, epidemiological and evolutive data were collected. Results: a total of 18 patients were included. Fifty-five percent received anti-programmed cell death protein 1 (PD-1)/anti-programmed death-ligand 1 (anti PD-L1), 11 % received anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and 33 % received both treatments. The toxicities were manifested as enterocolitis, microscopic colitis and gastritis. Upper gastrointestinal endoscopy was performed in seven patients; all were proved to have histological changes on duodenum biopsies. Treatment was stopped in all patients and steroids were initiated. Sixty-six per cent achieved clinical remission with steroids. Five patients received anti-TNF treatment (infliximab). Only one of the five had responded. Two anti-TNF refractory patients received ustekinumab, with an appropriate clinical response. One patient received apheresis granulocyte as concomitant treatment. A patient with a steroid-dependent course started vedolizumab. Three patients had other immune-related adverse events. Conclusion: gastrointestinal immune-related adverse events are acquiring a higher profile in daily practice and gastroenterologists play an even greater role in the management of these patients.

Severe and refractory gastrointestinal toxicity due to immune checkpoint inhibitors: clinical experience in a tertiary referral hospital – PubMed (nih.gov)

REED – Revista Española de Enfermedades Digestivas

Satoshi Tanida ^1 2, Keiji Ozeki ³, Takahito Katano ³, Mamoru Tanaka ³, Takaya Shimura ³, Eiji Kubota ³, Hiromi Kataoka ³, Takuya Takahama ², Shun Sasoh ², Yoshimasa Kubota ², Tesshin Ban ², Tomoaki Ando ², Makoto Nakamura ², Takashi Joh ²J Clin Med Res. 2023 Mar;15(3):181-186. doi: 10.14740/jocmr4887

Every-week (ew) adalimumab (ADA) maintenance following induction therapy with a standard induction regimen has recently been approved for use in Japan. The efficacy and safety of combination therapy with ew-ADA maintenance following standard induction regimen plus intensive granulocyte and monocyte adsorptive apheresis (GMA) (two sessions/week) for the treatment of refractory ulcerative colitis (UC) displaying failure of conventional, biologics and Janus kinase inhibitor have not been evaluated previously. The present retrospective study evaluated the 10-week efficacy of this combination therapy among refractory UC patients. Six patients were given initial ADA combination therapy (ADA at 160 mg in week 0, ADA 80 mg in week 2, and 40 mg in week 4, followed by ew-ADA at 40 mg/week) plus intensive GMA. One patient (16.6%) achieved clinical remission and two patients (33.3%) achieved endoscopic improvement by week 10. After excluding two patients who discontinued treatment, mean full Mayo score (P = 0.14), endoscopic subscore (P = 0.18) and C-reactive protein level (P = 0.27) at 10 weeks were numerically decreased compared with baseline in the remaining four cases, although the differences were not significant. Use of ew-ADA maintenance following standard induction regimen plus intensive GMA appears unlikely to achieve satisfactory induction of clinical remission in UC patients for whom conventional agents, biologics and Janus kinase inhibitors have failed.

Induction Therapy With a Combination of Weekly Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Ulcerative Colitis and Failure of Conventional Agents, Biologics and Janus Kinase Inhibitor – PubMed (nih.gov)

Induction Therapy With a Combination of Weekly Adalimumab Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis in Patients With Ulcerative Colitis and Failure of Conventional Agents, Biologics and Janus Kinase Inhibitor – PMC (nih.gov)

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)

Tomoyoshi Shibuya,Osamu Nomura,Kei Nomura,Mayuko Haraikawa,Keiichi Haga,Dai Ishikawa,Taro Osada,Ken Yamaji,Shigaku Ikeda,Akihito Nagahara

Ther Apher Dial 2022 Mar 5. doi: 10.1111/1744-9987.13823. Online ahead of print.

Introduction: In recent years, the prevalence of inflammatory bowel diseases has been increasing in Japan due to the westernization of lifestyles. Many patients have been reported to have extra-intestinal manifestations (EIMs) at least once. Skin lesions occur with a high degree of frequency among EIMs, with erythema nodosum (EN) and pyoderma gangrenosum (PG) the main complications. Cytapheresis is again attracting attention as a treatment with few side effects. Methods: We investigated the therapeutic effect of cytapheresis on ulcerative colitis (UC) and cutaneous EIMs. Between 2008 and 2021, 240 patients with active UC had induction therapy by cytapheresis at our hospital. Results: Remission and response rates were 50.0% and 67.5%, respectively. Apheresis was performed on seven patients with PG and five patients with EN with a good response. Serious adverse events were not observed. Conclusion: This retrospective assessment of efficacy showed that EN and PG responded favorably to cytapheresis.

https://pubmed.ncbi.nlm.nih.gov/35247233/

Víctor López Baez, Pedro Arango Sancho, Yolanda Calzada Baños, Elena Codina Sampera, Ana Vinuesa Jaca, Lina Hernández Zúñiga, Álvaro Madrid Aris, Nephrology Dialysis Transplantation, Volume 35, Issue Supplement_3

The apheresis techniques in pediatrics had been presented with few complications in our center, none derived from vascular access, anticoagulation, infections or adverse effects due to use of replacement fluid. The training of medical and nursing staff is essential to identify risk situations. The use of protocols and international guidelines ensure safety in pediatrics.

https://academic.oup.com/ndt/article/35/Supplement_3/gfaa140.MO079/5853667

OP-NDTJ_Perlims 1..15 (silverchair.com)