Granulocyte-monocyte Apheresis Research Articles

Combination of granulocyte–monocyte apheresis and ustekinumab: Multicentre and retrospective study

ObjectiveGranulocyte–monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. Patients and methodsA retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. 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. ResultsSeventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35–61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5–7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. ConclusionGMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug.

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

ObjectivePrimary 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 methodsA 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. ResultsNo 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. ConclusionsThe 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.

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

Abstract 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.

P106 Single-cell transcriptomic analysis reveals insights into the mechanism of action of Granulocyte-monocyte apheresis

Abstract Background Granulocyte-monocyte apheresis (GMA) is a non-pharmacological treatment approved for the management of ulcerative colitis (UC), particularly steroid-dependent cases. The exact mechanism of action and immunological changes associated with GMA remain undescribed. Gene expression analysis at the single-cell level (through scRNA-Seq) has emerged as a key tool of choice to characterize drug response at the molecular level. We used scRNA-Seq to characterize the transcriptomic effects and immune cell population alterations in GMA. Methods We generated scRNA-Seq from peripheral blood mononuclear cells (PBMC) of two ulcerative colitis (UC) patients undergoing GMA treatment. We compared the gene expression profile before and after 5 sessions of GMA treatment. The analytical pipeline included quality control and classical filtering steps, cell-type annotation, differential gene expression analysis and pathway enrichment profiling. Results We report three main results. First, we observed significant reductions of cell types directly affected by GMA treatment in UC patients. This includes classical CD14+ monocytes and Natural killers, which are central components of the innate system. Of note, we observed a remarkable increase in Double-negative T cells (dnT) after 5 sessions of GMA treatment, suggesting potential expansion of protective populations involved in decreased inflammation. Second, we observe a variety of genes and regulatory pathways altered by GMA treatment. In total, we detect 86 differentially expressed genes (DEGs), which overall are biased towards downregulation (63%). Of note, we detected dnT-s exhibiting upregulation of NEFL that is associated with the MAPK cascade and downregulation of genes related to immune response and signaling pathways. Finally, the effects of GMA treatment extend beyond the above mentioned populations, with particular alterations in CD4+ T cell populations such as CD4+ central memory and CD4+ Naive (7 and 13 DEGs, respectively). Conclusion For the first time, we generated single-cell transcriptomic profiles to characterize the effects of GMA treatment in peripheral blood of UC patients. Our preliminary analysis detects important alterations in the gene regulation and cell type composition in samples obtained after 5 sessions of GMA. Through expansion of this dataset to include more time points and profiles for more individuals, we will discuss the longitudinal changes and molecular mechanisms involved in response to GMA treatment.

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

ObjectiveGranulocyte–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 methodsRetrospective 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. ResultsTwelve 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. ConclusionThe combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug.

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

ObjectivePrimary 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 methodsA 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. ResultsNo 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. ConclusionsThe 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.

Pustular psoriasis: A distinct aetiopathogenic and clinical entity.

Pustular psoriasis is a distinct subset of psoriasis that presents with involvement of the skin in the form of sterile pustules along with systemic manifestations. Though it has been conventionally grouped under the umbrella of psoriasis, recent research has shed light on its pathogenetic mechanisms associated with the IL-36 pathway, which is distinct from conventional psoriasis. Pustular psoriasis in itself is a heterogeneous entity consisting of various subtypes, including generalised, localised, acute, and chronic forms. There is confusion regarding its current classification as entities like deficiency of IL-36 antagonist (DITRA) which are closely related to pustular psoriasis both in their pathogenetic mechanism and its clinical manifestations, are not included under pustular psoriasis. Entities like palmoplantar pustulosis, which presents with similar clinical features but is pathogenetically distinct from other forms of pustular psoriasis, are included under this condition. Management of pustular psoriasis depends upon its severity; while some of the localised variants can be managed with topical therapy alone, the generalised variants like Von Zumbusch disease and impetigo herpetiformis may need intensive care unit admission and tailor-made treatment protocols. The advent of newer biologics and better insight into the pathogenesis of pustular psoriasis has opened the way for newer therapies, including tumour necrosis factor-alpha inhibitors, interleukin-1 inhibitors, interleukin-17 inhibitors, and granulocyte monocyte apheresis. It continues to be an enigma whether pustular psoriasis is actually a variant of psoriasis or an entirely different disease entity, though we feel that it is an entirely different disease process.

Pyoderma gangrenosum in ulcerative colitis patient treated with vedolizumab: adsorptive granulocyte/monocyte apheresis as a new therapeutic option refractory cases – a case report and literature review

Extraintestinal manifestations occur rather frequently in ulcerative colitis (UC) and Crohn’s disease patients and are usually related to an exacerbation of the underlying intestinal bowel disease but sometimes may run a course independent of the inflammatory bowel diseases (IBD). About one-third of patients with IBD develop extraintestinal manifestations, such as pyoderma gangrenosum (PG). PG is an uncommon inflammatory skin disorder of unknown pathogenesis. There are no specific serological or histological markers, and diagnosis is predominantly clinical. Topical and systemic therapies are both vital aspects of treatment and immune modulators have been used with increasing success in recent years, although immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and comorbid patients, underlining the unmet need for safer alternative therapies. Thus, in this case report, we highlighted an adsorptive granulocyte/monocyte apheresis (GMA) as a new therapeutic possibility in IBD patients with extraintestinal manifestations. We report a case of a 60-year woman with a history of UC with a Mayo grade 3 score which was associated with a PG. Given that the patients maintained clinical remission with vedolizumab, we preferred not to perform a combined treatment with other antitumor necrosis factor-alpha or ciclosporin, thus avoiding an increased risk of serious infections in the patient. Therefore, we performed the extracorporeal leukocyte apheresis. The patient progressed favorably, with progressive improvement of skin and bowel disease. Therefore, adsorptive GMA has a very favorable safety profile and has been confirmed in numerous studies. In this study, we underlined that an intensive regimen of GMA paves the way to an ideal option for patients with severe and refractory PG complicated with UC.

Excellent Response to Secukinumab in Treatment Resistant Impetigo Herpetiformis.

Excellent Response to Secukinumab in Treatment Resistant Impetigo Herpetiformis.

Apheresis: A cell-based therapeutic tool for the inflammatory bowel disease.

Inflammatory Bowel Disease (IBD) is a hallmark of leukocyte infiltration, followed by the release of cytokines and interleukins. Disease progression to Ulcerative Colitis (UC) or Crohn’s Disease (CD) remained largely incurable. The genetic and environmental factors disrupt enteral bacteria in the gut, which hampers the intestinal repairing capability of damaged mucosa. Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor (TNF)-α. New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response. This review discusses the non-pharmacologic selective granulocyte–monocyte-apheresis (GMA) and leukocytapheresis (LCAP) that have been proposed as treatment modalities that reduce mortality. GMA, an extracorporeal vein-to-vein technique, presents a strong safety profile case for its use as a viable therapeutic option compared to GMA's conventional medication safety profile. GMA reported minimal to no side effects in the pediatric population and pregnant women. Numerous studies report the efficacious nature of GMA in UC patients, whereas data on CD patients is insufficient. Its benefits outweigh the risks and are emerging as a favored non-pharmacological treatment option. On the contrary, LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release. It has been deemed more efficacious than conventional drug treatments, the former causing better disease remission, and maintenance. Patients with UC/CD secondary to complications have responded well to the treatment. Side effects of the procedure have remained mild to moderate, and there is little evidence of any severe adverse event occurring in most age groups. LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD. The review will discuss the role of GMA and LCAP.

Ulcerative colitis complicated by pyoderma gangrenosum and multiple aseptic abscesses

A woman in her 30s was diagnosed with ulcerative colitis (UC) 4 years ago and treated with tacrolimus, azathioprine, and prednisolone 5mg (PSL). Skin ulcers appeared on the right lower leg during the course of treatment, diagnosed as pyoderma gangrenosum (PG). The patient initially improved with an increased PSL and infliximab dose, but then developed multiple skin ulcers and folliculitis throughout her body. She was transferred to our hospital for PG exacerbation treatment. She developed fever after transfer and contrast-enhanced computed tomography showed multiple abscesses in the lungs and kidneys. PSL was decreased and infliximab was discontinued. Antibiotic therapy and granulocyte/monocyte apheresis (GMA) were started. Fever persisted even after antibiotic treatment, and her general condition did not improve. A right renal abscess puncture was performed. Pus was sterile. A sterile abscess associated with PG was suspected. The PSL dose was increased to 1mg/kg and infliximab restarted. Thereafter, the patient's general condition improved, and both lung and renal abscesses contracted. Skin ulcer epithelialization was also observed. Abdominal symptoms were mild during the course of the disease, and colonoscopy showed only a localized ulcerative lesion in the rectum. The patient was later transferred to the department of dermatology at our hospital for PG treatment. Aseptic abscesses are caused by neutrophil infiltration without infection and have been reported to be associated with neutrophilic dermatosis and inflammatory bowel disease. UC-associated aseptic abscess is rare. This is only the sixth case in Japan. Aseptic abscesses can occur in various sites, including subcutaneous and deep organs, but this is the first kidney abscess case. In previous reports, PSL, infliximab, colchicine, and infliximab+GMA were used for aseptic abscesses associated with UC. They all showed abscess reduction. Aseptic abscesses associated with PG should be considered if abscess lesions occur during the course of UC, and a treatment strategy including enhanced immunosuppression should be considered.

De novo ulcerative colitis after kidney transplantation treated with infliximab

Diarrhea is a common complication in kidney transplant recipients. Common causes of diarrhea include infection, side effect from medication, rejection, and malignancy. A less common but important cause of diarrhea is de novo inflammatory bowel disease (IBD). This is unexpected, as these patients are already immunosuppressed. Herein, we present the case of a 45-year-old man with end-stage kidney disease because of focal segmental glomerulosclerosis who underwent preemptive kidney transplantation, with his mother as donor. His immunosuppressive regimen included methylprednisolone, mycophenolate mofetil, and tacrolimus. He had no episodes of graft dysfunction, rejection, or infectious events. Two and a half years post-transplantation, he developed bloody diarrhea. After excluding infections, colonoscopy was performed and revealed edematous mucosa and erythema with pigmentation, which are typical findings in ulcerative colitis. Despite therapy with 5-aminosalicylate and granulocyte monocyte apheresis, he presented with massive bloody diarrhea. We initiated infliximab, an anti-tumor necrosis factor-α (TNF-α) agent. He responded very well and achieved remission within 6 months after initiation of infliximab, while administration of the other immunosuppressants was maintained. His course was uneventful and no complications developed. Management of immunosuppressants for de novo IBD after organ transplantation is complicated, because treatment of IBD, graft function protection, and prevention of infection must be considered. Therefore, cooperation between transplantation physicians and gastroenterologists is essential during therapy.

The combination of granulocyte-monocyte apheresis and vedolizumab: A new treatment option for ulcerative colitis?

To assess the effectiveness and safety of combining granulocyte-monocyte apheresis (GMA) and vedolizumab (VDZ) in patients with refractory ulcerative colitis (UC). This retrospective, multicentre pilot study included all UC patients receiving both GMA and VDZ. We recorded data on GMA sessions, demographic characteristics, and clinical response. Effectiveness was assessed 1 and 6 months after finishing the GMA using the partial Mayo score, C-reactive protein, and fecal calprotectin levels. Data were also compiled on VDZ intensification, use of new immunomodulators and colectomy during follow-up. Eight patients were included (mean age 46 years; 63% female; mean disease duration, 132 months; 50% E3). GMA was started after a loss of response to VDZ in all cases (25% primary nonresponse and 75% secondary loss of response). All had previously received anti-TNF agents. VDZ was prescribed as the second-, third-, or fourth-line biologic in 37%, 50%, and 13% of cases, respectively. Patients had a mean baseline partial Mayo score of 7.5 (SD 2.1) and received a median of 15 GMA sessions (range 5-38). After a median follow-up of 7.5 months (IQR 5-12), partial Mayo score decreased after 1 and 6 months (P = .01 and .06, respectively). Three patients (38%) achieved steroid-free clinical remission and five (63%) withdrew VDZ. Colectomy rate was 38%. No adverse events were observed during the combination therapy. This small case series suggests that combining GMA with VDZ could be a treatment option in selected cases of UC with an inadequate response to this biologic agent.

Granulocyte–monocyte apheresis: an alternative combination therapy after loss of response to anti-TNF agents in ulcerative colitis

Objective: To evaluate the effectiveness and safety of the combination of granulocyte–monocyte apheresis (GMA) after loss of response (LOR) to anti-tumor necrosis factor (TNF) agents in ulcerative colitis (UC).Materials and methods: A retrospective, multicenter study was performed in 11 inflammatory bowel disease (IBD) Units. Clinical remission was defined as a partial Mayo score ≤2. The effectiveness of the treatment was evaluated by the partial Mayo score and the rate of anti-TNF intensification, switch, swap or colectomy.Results: Forty-seven patients with ulcerative colitis were included (mean age 35 years, mean disease duration 52 months, 66% male and 59% extensive colitis). Twenty-three subjects were receiving infliximab, eighteen adalimumab and six golimumab. GMA was combined after a primary non-response (49%) or secondary loss of response (51%) to anti-TNF therapy. We observed a significant decrease in partial Mayo score and fecal calprotectin after GMA. Fifteen patients (32%) responded to the combination therapy without anti-TNF intensification, switch, swap or colectomy. Eight patients (17%) underwent colectomy. Two patients (4%) presented adverse events related to the technique.Conclusions: Combination of GMA and anti-tumor necrosis factor is a safe and effective treatment after the loss of response to these biologic agents, with a significant decrease of the clinical disease activity and biomarkers, in a population with limited therapeutic alternatives.

EP06.31: Constriction of intrahepatic umbilical vein and loss of fetal movement during granulocyte monocyte apheresis for generalised pustular psoriasis: a case report

EP06.31: Constriction of intrahepatic umbilical vein and loss of fetal movement during granulocyte monocyte apheresis for generalised pustular psoriasis: a case report

Mucosal Cytokine Profiles After Induction Therapy With Granulocyte/Monocyte Apheresis in New-onset Inflammatory Colitis.

Granulocyte/monocyte apheresis (GMA) selectively removes circulating granulocytes and monocytes; important producers of proinflammatory cytokines. Seven children with new-onset inflammatory bowel disease (IBD) colitis were treated with GMA together with mesalazine, and had significant decreases in Pediatric UC Activity Index (P = 0.018) and Mayo endoscopic score (P = 0.013). We investigated the colonic mucosal cytokine profiles (analyzed with real-time polymerase chain reaction), before and after induction treatment, and in 6 non-IBD controls. Significant decreases were seen in Colony Stimulating Factor 2 (P = 0.018), tumor necrosis factor-α (P = 0.028), interleukin (IL)-23α (P = 0.043), IL-1β (P = 0.028), IL-36γ (P = 0.018), IL-10 (P = 0.028), and transforming growth factor beta 1 (P = 0.043) after treatment. In 6 non-IBD controls there were significantly lower levels of IL-12β (P = 0.023) and IL-23α (P = 0.046) compared to the patients with IBD at onset, and IL-22 (P = 0.088) and IL-36γ (P = 0.062) showed lower values without reaching significant differences. We speculate that the decreases in colonic mucosal cytokine profiles after treatment may explain the observed clinical efficacy in the GMA-treated children with IBD.

P560 Granulocyte–monocyte apheresis combination therapy after loss of response to anti-TNF drugs

Granulocyte–monocyte apheresis (GMA) selectively removes activated leukocytes and some immune mediators, and it is safe and effective in ulcerative colitis (UC). Anti-TNF drugs are also effective in moderate–severe UC but a significant proportion of patients does not respond during the induction phase or lose response over time. The aim of our study was to evaluate the clinical efficacy and safety of the combination of GMA sessions after primary or secondary loss of response to anti-TNF therapy. A retrospective, multicentre study was performed in six inflammatory bowel disease (IBD) Units in Spain. We collected data on the disease phenotype, previous medications and past relevant history of the disease. Regarding the GMA therapy the number of sessions, its frequency, filtered blood volume and time of each session were recorded. The efficacy of the treatment was assessed by clinical and analytical parameters 1 and 6 months after finishing the GMA. The need for rescue therapy and colectomy were compiled during the follow-up. Twenty-seven patients (38 years [IQR 28–48], 63% male, disease duration 47 months [IQR 36–105]) were included. Most of them had a previous diagnosis of UC (93%), 1 of CD and 1 of IBD-U. Fourteen were on infliximab, 10 on adalimumab and 3 on golimumab; 67% under dose/frequency optimisation. GMA was used more frequently after secondary loss of response (74%) and 63% of patients received ≥10 sessions. Fifteen patients (56%) were on their first-line biologic therapy, while 44% have received at least one previous anti-TNF. Partial Mayo score at baseline was 6 (IQR 5–8). Clinical disease activity significantly decreased after 1 month (2 [IQR 1–7]) and 6 months (1.5 [IQR 0–6]), both p < 0.005. Baseline CRP was 2.2 mg/l (IQR 0.6–8.9), albumin 3.4 g/l (IQR 2.9–4), haemoglobin 11.4 g/dl (IQR 10.8–12.8) and calprotectin 2,239 mg/kg (IQR 1, 189–3, 150). CRP and calprotectin decreased after 1 month (p = 0.5 and 0.008) and 6 months (p = 0.05 and 0.04),respectively. One patient reported adverse events related to the technique (anxiety). Median follow-up was 30.5 months (IQR 11–64). Eight patients (30%) achieved steroid-free remission without anti-TNF intensification, switch of biologic or surgery. Five patients were able to de-escalate therapy. Seven patients (26%) required dose optimisation of the anti-TNF. Nine patients (33%) started a new biologic therapy and three (11%) underwent colectomy during the during the first-year follow-up. Combination of GMA and anti-TNF drugs offers a safe and effective alternative after loss of response to biologics, with a significant decrease in the clinical disease activity and biomarkers, in a population with limited therapeutic options.

Inflammatory bowel disease patients experiencing a loss of response to infliximab regain long-term response after undergoing granulocyte/monocyte apheresis: A case series

Up to 50% of patients with ulcerative colitis (UC) or Crohn’s disease (CD) experience a loss of response (LOR) to infliximab after an initial response to the drug. Granulocyte/monocyte apheresis (GMA) with the Adacolumn depletes the activated myeloid leukocytes that are known to exacerbate and perpetuate inflammatory bowel diseases, but GMA has hitherto not been applied to patients with LOR to infliximab. We report three cases (2 UC and 1CD) with LOR to maintenance infliximab therapy that received one GMA session/week for 3 consecutive weeks or more. The disease severity was assessed from the CD activity index or partial Mayo score, and the trough infliximab (TI) level was measured. Upon GMA therapy, all three patients achieved remission for up to 15 months with maintenance infliximab alone. The average plasma TI increased from 0.91 μg/mL to 1.46 μg/mL, with concomitant decreases of C-reactive protein (from 2.33 mg/dL to 0.78 mg/dL), interleukin-6 (from 8.4 pg/mL to 3.4 pg/mL), and interleukin-17A (from 0.21 pg/mL to 0.03 pg/mL). 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.

Adsorptive Depletion of Myeloid Lineage Leucocytes as Remission Induction Therapy in Patients with Ulcerative Colitis after Failure of First-Line Medications: Results from a Three-Year Real World, Clinical Practice

Background/Aims: In patients with active ulcerative colitis (UC), pharmacologics, although initially effective in most patients, are associated with refractoriness, loss of response or unfavourable side effects as additional morbidity factors. Depletion of myeloid lineage leucocytes like the CD14(+)CD16(+) monocyte phenotype, which is a major source of tumour necrosis factor-α, by granulocyte/monocyte apheresis (GMA) if effective, is also known to be free from side effects. Methods: In clinical practice setting, 77 consecutive patients with moderate to severe UC, who failed to respond to first-line medications received GMA with the Adacolumn as remission induction therapy. Patients who achieved remission were followed for 3 years. Results: Among the 77 patients, 46.8% were corticosteroids-naïve, 26% corticosteroid-dependent and 27.3% corticosteroid-refractory. The overall clinical remission rate was 79.2%, and the overall mucosal healing (MH) rate according to the Mayo endoscopic subscore ≤1 was 58.5%. MH rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 70.8, 56.3, and 38.5%, respectively. The 3-year sustained clinical remission rates in corticosteroid-naïve, corticosteroid-dependent and corticosteroid-refractory subgroups were 83.3, 68.8, and 23.1%, respectively. Conclusion: Corticosteroid-naïve patients appeared to benefit the most from the Adacolumn GMA, and attain a favourable long-term clinical course. Accordingly, GMA should be a first-line therapy in this clinical setting.

10 Granulocyte/monocyte apheresis as maintenance therapy in crohn’s disease

Background Granulocyte, monocyte apheresis (GMA), extra-corporeal absorptive circuit used to treat acute ulcerative colitis (UC) and Crohn’s disease. Use in maintenance therapy following remission is uncertain. Aim To present the outcomes following treatment of 5 patients with maintenance GMA for Crohn’s disease. Method Notes review of patients. Assessed blood results (full blood count, albumin, c-reactive protein) faecal calprotectin (FC), imaging and subjective patient reporting to determine the response Results 5 patients (P) were included, of whom: 4 were male, mean age 37.4 (24–57) years. All received previous conventional therapies with no or limited effect or had lost response. All had 8 treatments at weekly intervals as acute therapy followed by maintenance at monthly intervals. P1 (30 year old male, small bowel (SB) Crohn’s), 40 columns, consistent normalisation in all markers and FC (from >600 to 248), reversal of temporary colostomy, improvement on MRE, subjective improvement. P 2 (46 year old male, SB Crohn’s) 12 columns, consistent improvement in bloods, subjectively in remission. P3 (24 year old male, Crohn’s colitis) 9 columns, initial subjective improvement, bloods unchanged from baseline but normal, switched to vedolizumab. P4 (30 year old male, SB Crohn’s) 5 columns, no subjective change, stopped. P5 (57 year old female, SB Crohn’s) 4 columns, improvement in C-reactive protein, others consistently normal, no change from baseline, subjective improvement but stopped. Conclusions Five patients received maintenance therapy. Consistent biochemical/subjective symptomatic remission was achieved in two (P1 and 2), subjective remission in a third (P5) but no response in P3 and 4. Remission appeared to continue in those with elevated baseline markers of inflammation. SB Crohn’s may respond better than colitis. GMA may have a role as maintenance therapy.