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, doi.org=10.1093/ecco-jcc/jjad212.0712

Background
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.

Methods
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.

Results
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.

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

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

Yixue Liu, Xiaoping Tan

Inflammatory bowel disease (IBD) is a group of chronic, nonspecific intestinal inflammatory disorders characterized by localized and systemic inflammation. The use of biologic agents in the treatment of IBD patients is widespread, and the occurrence of primary non-responsiveness during treatment is also significant. This review briefly summarizes the possible reasons for primary non-responsiveness in IBD patients, as well as predictive markers and current strategies to address it, providing a theoretical reference for early identification and management of IBD patients who do not respond to treatment.

Iago Rodríguez-Lago ¹, Leticia Abecia ², Iratxe Seoane ², Juan Anguita ³, José Luis Cabriada ⁴Gastroenterol Hepatol. 2023 Jul 6:S0210-5705(23)00370-9. doi: 10.1016/j.gastrohep.2023.07.001.[Article in English, Spanish]

Objective: Primary non-response and secondary loss of response to anti-TNF agents are common in inflammatory bowel disease. Increasing drug concentrations are correlated to better clinical response and remission rates. Combination of granulocyte-monocyte apheresis (GMA) with anti-tumor necrosis factor (TNF) agents could be an option in these patients. The objective of our study was to perform an in vitro assay to determine if the GMA device can lead to infliximab (IFX) adsorption.

Patients and methods: A blood sample was obtained from a healthy control. It was incubated with three concentrations of IFX (3, 6, and 9μg/ml) at room temperature for 10min. At that time, 1ml was collected to determine the IFX concentration. Then, 10ml of each drug concentration was incubated with 5ml of cellulose acetate (CA) beads from the GMA device at 200rpm for 1h at 37°C to simulate physiological human conditions. A second sample of each concentration was collected and IFX levels were determined.

Results: No statistically significant differences were observed in the IFX levels in the blood samples before and after incubation with the CA beads (p=0.41) and after repeated measurements (p=0.31). Mean change was 3.8μg/ml.

Conclusions: The in vitro combination of GMA and IFX did not change the circulating levels of IFX at the three concentrations tested, suggesting that there is no interaction between the drug and the apheresis device in vitro and that they might be safely combined with each other.

An in vitro analysis of the interaction between infliximab and granulocyte-monocyte apheresis – PubMed (nih.gov)

An in vitro analysis of the interaction between infliximab and granulocyte–monocyte apheresis – ScienceDirect