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P582 Combination of granulocyte–monocyte apheresis and ustekinumab: multicentre and retrospective study

I Rodríguez-Lago, C Herrera-deGuise, M Boscá-Watts, C Rodríguez, E Leo, M Calvo, F Cañete, S Chacón, C Cuarán, A Elorza, E Guerra, E Iglesias, D Sánchez, M Barreiro-de Acosta, D Ginard, J L Cabriada Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Page i1135,

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, mainly with anti-TNF.

The aim of our study was to evaluate the clinical efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. A retrospective, multicentric study was performed in 12 IBD Units, including all patients with refractory UC who received combined GMA plus UST. The number of GMA sessions, its frequency, filtered blood volume and time of each session were compiled, along with the clinical data. Efficacy was assessed 1 and 6 months after finishing the GMA by partial Mayo score, CRP and faecal calprotectin. Data regarding UST intensification, need for new immunomodulators/biologics and surgery were also compiled. Descriptive statistics and non-parametric tests were used in the statistical analysis.

Nineteen patients were included (15 UC, 2 Crohn’s disease, 2 unclassified IBD; median age 48 years (IQR, 36-63); 68% male). At baseline, 78% were receiving steroids and 23% immunomodulators. Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab. Baseline Mayo score was 6.5 (IQR, 5-7), with a median CRP of 9 mg/L (IQR, 4.8-20.8) and faecal calprotectin 1,612 mg/kg (IQR, 873-4,152). GMA was started mostly after PNR in 83%, the median number of GMA sessions was 16 (IQR, 11-27) and 50% of patients started maintenance GMA. Partial Mayo score significantly decreased 6 months after the last GMA session (p=0.019). During follow-up, 27% started a new biologic therapy and 13% required surgery. 64% of patients under steroids at baseline were able to stop them. Adverse events were reported in 5% of patients.

GMA can safely recapture the response to UST in refractory patients after PNR or LOR to this drug.

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Combination of granulocyte-monocyte apheresis and tofacitinib: Multicentre and retrospective study

Iago Rodríguez-Lago 1, Fiorella Cañete 2, Elena Guerra-Del-Río 3, Claudia Herrera-deGuise 4, Eva Iglesias 5, Eduardo Leo 6, Yamile Zabana 7, Manuel Barreiro-de Acosta 8, Daniel Ginard 9, José Luis Cabriada 10
Gastroenterol Hepatol. 2024 Jan 23:S0210-5705(24)00022-0. doi: 10.1016/j.gastrohep.2024.01.004. Online ahead of print.
[Article in English, Spanish]

Objective: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is 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.

Patients and methods: Retrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results: Twelve patients were included (median 46 years [IQR, 37-58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5-7), and it decreased to a median of 2 (IQR, 0-3) and 0 (IQR, 0-3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them. Conclusion: The combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug

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Adsorptive cytapheresis in ulcerative colitis: A non-pharmacological therapeutic approach revisited

Filippo Vernia 1Angelo Viscido 1Giovanni Latella 1J Clin Apher. 2023 Dec;38(6):746-754

Adsorptive cytapheresis proves effective in a proportion of patients affected by ulcerative colitis. Relatively high cost and the need for apheresis facilities, prevented the widespread use of this therapeutic approach. More so following the introduction of anti-TNFα biosimilars which proved both effective and inexpensive. Anti-TNFα agents, however, are burdened by high rate of primary and secondary non-response and prompt switching to new, high-cost biologics, and small molecules. The present review analyzes advantages and disadvantages of adsorptive cytapheresis in the present clinical scenario and suggests its repositioning in the therapeutic workup of selected subgroups of ulcerative colitis patients. The extremely favorable safety profile makes adsorptive cytapheresis a viable therapeutic option in elderly and high-risk UC patients, as well as potential second-line treatment in corticosteroid-dependent patients and poor responders to first-line biologics.

Adsorptive cytapheresis in ulcerative colitis: A non-pharmacological therapeutic approach revisited – PubMed (

Adsorptive cytapheresis in ulcerative colitis: A non‐pharmacological therapeutic approach revisited – Vernia – 2023 – Journal of Clinical Apheresis – Wiley Online Library

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The clinical efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with Crohn’s disease: A multicenter retrospective cohort study

Nobuhiro Ueno Seisuke Saito Masahiro Sato Yuya Sugiyama doi: 10.21203/

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 (

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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.

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S-05-06 Efficacy of Adsorptive Granulocyte/Monocyte Apheresis in Inflammatory Bowel Disease Patients Experiencing Loss of Response to Infliximab (poster)


To our knowledge this is the first report of adding GMA to restore the efficacy of infliximab in patients with LoR.  However, the efficacy outcomes following addition of a non-drug GMA to infliximab is potentially very interesting in therapeutic settings and should inspire further studies

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Novel Prognostic Biomarkers of Mucosal Healing in Ulcerative Colitis Patients Treated With Anti-TNF: Neutrophil-toLymphocyte Ratio and Platelet-to-Lymphocyte Ratio

Lorenzo Bertani 1Federico Rossari 2Brigida Barberio 3Maria Giulia Demarzo 4Gherardo Tapete 1Eleonora Albano 1Giovanni Baiano Svizzero 1Linda Ceccarelli 5Maria Gloria Mumolo 5Chiara Brombin 6Nicola de Bortoli 1Massimo Bellini 1Santino Marchi 1Giorgia Bodini 4Edoardo Savarino 3Francesco Costa 5

Inflamm Bowel Dis. 2020 Sep 18;26(10):1579-1587. doi: 10.1093/ibd/izaa062.

Background: Anti-tumor necrosis factor drugs (anti-TNFs) are widely used for the treatment of ulcerative colitis (UC). However, many patients experience loss of response during the first year of therapy. An early predictor of clinical remission and mucosal healing is needed. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of subclinical inflammation poorly evaluated in UC patients treated with anti-TNFs. The aim of this multicenter study was to evaluate whether NLR and PLR could be used as prognostic markers of anti-TNF treatment response. Methods: Patients with UC who started anti-TNF treatment in monotherapy were evaluated. Patients with concomitant corticosteroid treatment ≥20 mg were excluded. We calculated NLR, PLR, and fecal calprotectin before treatment and after induction. The values of NLR and PLR were correlated with clinical remission and mucosal healing at the end of follow-up (54 weeks) using the Mann-Whitney U test and then multivariate analysis was conducted. Results: Eighty-eight patients were included. Patients who reached mucosal healing after 54 weeks of therapy displayed lower levels of both baseline NLR and PLR (P = 0.0001 and P = 0.04, respectively); similar results were obtained at week 8 (P = 0.0001 and P = 0.001, respectively). Patients who presented with active ulcers at baseline endoscopic evaluation had higher baseline NLR and PLR values compared with those without detected ulcers (P = 0.002 and P = 0.0007, respectively). Conclusions: Both NLR and PLR showed a promising role as early predictors of therapeutic response to anti-TNF therapy in UC patients. If confirmed in larger studies, classification and regression trees proposed in this article could be useful to guide clinical decisions regarding anti-TNF treatment.

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Pyoderma gangrenosum associated with ulcerative colitis: A recalcitrant case responded to adalimumab with granulocyte and monocyte adsorption apheresis

Yuki Isami,Yuriko Kawase,Akari Kondo,Wataru Akita,Koji Yasuda,Takeshi Matsutani,Hiroshi Mitsui

J Dermatol. 2020 May;47(5):e213-e215. doi: 10.1111/1346-8138.15303. Epub 2020 Mar 11.


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Case Report: Combination Therapy With Granulocyte Apheresis and Infliximab for Refractory Crohn’s Disease

P. Gonzalez Carro, F. Perez Roldan, O. Roncero Garcıa Escribano,R. Lafuente, M.L. Legaz Huidobro, and A. Amigo Echenagusıa

Journal of Clinical Apheresis 21: 249–251 (2006)

To our knowledge, no cases of combined therapy with infliximab and granulocyte apheresis have been previously reported. Our results suggest that this combined therapy is a possible alternative to treat CD patients in the event of loss of response to infliximab.

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