Combination of granulocyte-monocyte apheresis and ustekinumab: Multicentre and retrospective study.

OBJECTIVE: Granulocyte-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 METHODS: A 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. RESULTS: Seventeen 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. CONCLUSION: GMA 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 / Análisis in vitro de la interacción entre infliximab y la aféresis de granulocitos y monocitos

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. (AU)

Objetivo: La falta de respuesta primaria y la pérdida de respuesta secundaria a los agentes antifactor de necrosis tumoral (TNF) son comunes en la enfermedad inflamatoria intestinal. El aumento de los niveles de fármaco se correlaciona con una mejor respuesta clínica y de las tasas de remisión. La combinación de la aféresis selectiva de granulocitos y monocitos (GMA) con agentes anti-TNF podría ser una opción en estos pacientes. El objetivo de nuestro estudio fue realizar un ensayo in vitro para determinar si el dispositivo de GMA puede interaccionar con infliximab (IFX). Pacientes y métodos: Se obtuvo una muestra de sangre de un control sano. Se incubó con 3 concentraciones de IFX (3, 6 y 9μg/ml) a temperatura ambiente durante 10 minutos. En ese momento, se recogió 1ml para determinar la concentración de IFX. Luego, se incubaron 10ml de cada concentración de fármaco con 5ml de cuentas de acetato de celulosa del dispositivo GMA a 200rpm durante una hora a 37°C para simular las condiciones fisiológicas humanas. Se recogió una segunda muestra de cada concentración y se determinaron los niveles de IFX. Resultados: No se observaron diferencias estadísticamente significativas en los niveles de IFX en las muestras de sangre antes y después de la incubación con las cuentas de acetato de celulosa (p=0,41) ni tras mediciones repetidas (p=0,31). La media de cambio fue de 3,8μg/ml. Conclusiones: La combinación in vitro de IFX y GMA no modificó los niveles circulantes del fármaco en las 3 concentraciones probadas, lo que indica que no existe interacción entre el fármaco y el dispositivo de aféresis in vitro y que podrían combinarse de forma segura. (AU)

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

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.

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

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.

A case of refractory immune checkpoint inhibitor-induced colitis improved by the treatment with vedolizumab and granulocyte-monocyte apheresis combination therapy.

A 68-year-old man developed immune-related adverse event (irAE) colitis after the initiation of nivolumab and ipilimumab combination therapy for malignant melanoma. We diagnosed the patient with grade 3 irAE colitis and started prednisolone (1 mg/kg/day). Although the symptom improved once, it worsened along with the tapering of prednisolone. Therefore, we started infliximab (IFX). However, symptoms did not improve after two doses of IFX. We discontinued IFX and initiated vedolizumab (VED). Because VED alone did not improve the symptom, we started granulocyte-monocyte apheresis (GMA). Twelve weeks after the onset, the colitis was in remission. Therefore, in addition to vedolizumab, GMA may be considered in cases refractory to treatment.

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.

Granulocyte and monocyte/macrophage apheresis in paediatric patients with ulcerative colitis: a case series in Spain.

Paediatric ulcerative colitis (UC) can cause malnutrition and growth retardation but its treatment can be limited by the potential adverse events of corticosteroids and anti-TNF agents in children. However, adsorptive granulocyte monocyte/macrophage apheresis (GMA) using Adacolumn® reduces intestinal inflammation through multiple immunomodulatory effects. This case series shows the safety and efficacy of GMA in paediatric UC, illustrating several GMA uses: in chronically active UC, for corticosteroid reduction in steroid-dependent UC, in UC with secondary loss of response to anti-TNF therapy, as bridge therapy in UC with failure of anti-TNF therapy, and to substitute toxic drug treatments.

Fecal calprotectin is a useful biomarker for predicting the clinical outcome of granulocyte and monocyte adsorptive apheresis in ulcerative colitis patients: a prospective observation study.

BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) is widely used as a remission induction therapy for active ulcerative colitis (UC) patients. However, there are no available biomarkers for predicting the clinical outcome of GMA. We investigated the utility of Fecal calprotectin (FC) as a biomarker for predicting the clinical outcome during GMA therapy in active UC patients. METHODS: In this multicenter prospective observation study, all patients received 10 sessions of GMA, twice a week, for 5 consecutive weeks. FC was measured at entry, one week, two weeks, and at the end of GMA. Colonoscopy was performed at entry and after GMA. The clinical activity was assessed based on the partial Mayo score when FC was measured. Clinical remission (CR) was defined as a partial Mayo score of ≤ 2 and endoscopic remission (ER) was defined as Mayo endoscopic subscore of either 0 or 1. We analyzed the relationships between the clinical outcome (CR and ER) and the change in FC concentration. RESULT: Twenty-six patients were included in this study. The overall CR and ER rates were 50.0% and 19.2%, respectively. After GMA, the median FC concentration in patients with ER was significantly lower than that in patients without ER (469 mg/kg vs. 3107 mg/kg, p = 0.03). When the cut-off value of FC concentration was set at 1150 mg/kg for assessing ER after GMA, the sensitivity and specificity were 0.8 and 0.81, respectively. The FC concentration had significantly decreased by one week. An ROC analysis demonstrated that the reduction rate of FC (ΔFC) at 1 week was the most accurate predictor of CR at the end of GMA (AUC = 0.852, P = 0.002). When the cut-off value of ΔFC was set at ≤ 40% at 1 week for predicting CR at the end of GMA, the sensitivity and specificity were 76.9% and 84.6%, respectively. CONCLUSION: We evaluated the utility of FC as a biomarker for assessing ER after GMA and predicting CR in the early phase during GMA in patients with active UC. Our findings will benefit patients with active UC by allowing them to avoid unnecessary invasive procedures and will help establish new strategies for GMA.

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.

Granulocyte and monocyte apheresis in inflammatory bowel disease: The patients' point of view.

BACKGROUND: Granulocyte and monocyte apheresis is the main non-pharmacological treatment for inflammatory bowel disease (IBD), but we do not know how well accepted it is by patients in our setting. AIM: To determine how granulocyte and monocyte apheresis is perceived by patients in clinical practice in Spain. METHODS: Outpatients treated with granulocyte and monocyte apheresis in five IBD Units in Spain were asked to fill in a 14-item questionnaire. RESULTS: Fifty-two patients completed the questionnaire (88% ulcerative colitis, 12% Crohn's disease; 44% female; age 35 years [IQR 23-51]). Granulocyte and monocyte apheresis was generally well tolerated and well accepted. Very few of the participants regarded the length of the sessions as a limitation. The gastrointestinal symptoms, however, were a frequent concern, both in terms of attending to receive treatment and during the sessions. Overall, 44% were satisfied with the treatment effectiveness. Sixty percent (60%) claimed to be satisfied with the therapy overall, but this was influenced by the patients' clinical response to the therapy. Eighty-two percent (82%) of participants said they would agree to be treated with this technique again in the future, regardless of the response to the treatment. CONCLUSIONS: Granulocyte and monocyte apheresis is well tolerated and accepted by patients with IBD. Although we found no significant differences according to type of IBD or apheresis regimen, patient perception was affected by clinical effectiveness.

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 Granulocyte and Monocyte Apheresis in the Treatment of Ulcerative Colitis: The First Multicenter Study in China.

BACKGROUND/AIMS: Patients with active ulcerative colitis (UC) have elevated levels of activated myeloid-derived leukocytes as a source of inflammatory cytokines. The selective depletion of these leukocytes by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn should alleviate inflammation, promote remission and enhance drug efficacy. However, studies have reported contrasting efficacy outcomes based on patients' baseline demographic variables. This study was undertaken to understand the demographic features of GMA responders and nonresponders. METHODS: This was a multicenter study in China involving four institutions and 34 patients with active UC. Baseline conventional medications were continued without changing the dosage. The treatment efficacy was evaluated based on the endoscopic activity index and the Mayo score. RESULTS: Thirty of the 34 patients completed all 10 GMA treatment sessions. The overall efficacy rate was 70.59%. The receiver operating characteristic analysis showed that the area under the curve was approximately 0.766 for a Mayo score of ≤5.5 with 0.273 specificity and 0.857 sensitivity (Youden index, 0.584) for GMA responders. No GMA-related serious adverse events were observed. CONCLUSIONS: The overall efficacy of GMA in patients with active UC who were taking first-line medications or were corticosteroid refractory was encouraging. Additionally, GMA was well tolerated and had a good safety profile.

Adsorptive Granulocyte and Monocyte Apheresis in the Treatment of Ulcerative Colitis: The First Multicenter Study in China

BACKGROUND/AIMS: Patients with active ulcerative colitis (UC) have elevated levels of activated myeloid-derived leukocytes as a source of inflammatory cytokines. The selective depletion of these leukocytes by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn should alleviate inflammation, promote remission and enhance drug efficacy. However, studies have reported contrasting efficacy outcomes based on patients’ baseline demographic variables. This study was undertaken to understand the demographic features of GMA responders and nonresponders. METHODS: This was a multicenter study in China involving four institutions and 34 patients with active UC. Baseline conventional medications were continued without changing the dosage. The treatment efficacy was evaluated based on the endoscopic activity index and the Mayo score. RESULTS: Thirty of the 34 patients completed all 10 GMA treatment sessions. The overall efficacy rate was 70.59%. The receiver operating characteristic analysis showed that the area under the curve was approximately 0.766 for a Mayo score of ≤5.5 with 0.273 specificity and 0.857 sensitivity (Youden index, 0.584) for GMA responders. No GMA-related serious adverse events were observed. CONCLUSIONS: The overall efficacy of GMA in patients with active UC who were taking first-line medications or were corticosteroid refractory was encouraging. Additionally, GMA was well tolerated and had a good safety profile.

Efficacy of a Novel Granulocyte Monocyte Apheresis Adsorber Device in the Treatment of Inflammatory Bowel Diseases: A Pilot Study.

Granulocyte monocyte apheresis (GMA) is a non-pharmacological treatment for inflammatory bowel disease. In our study, we tested a novel GMA adsorber device in terms of clinical efficacy and safety in patients' non-response to pharmacological therapy. Secondary outcomes were the evaluation of adsorber's technical performance, the reduction of inflammatory markers and the improvement of patients' life quality. The prospective study included 18 patients enrolled from 2011 to 2012 with a monitoring of 48 weeks. All patients with Crohn's disease achieved a clinical remission after GMA treatments, sustained until the end of follow up, while 80% of ulcerative colitis patients obtained a clinical benefit, maintained after 48 weeks of monitoring. Leukocytes, neutrophils, monocytes and platelets, compared to erythrocytes and lymphocytes, were effectively removed from peripheral blood. There was no statistically significant result about serological markers of inflammation. A consistent improvement of the patients' quality of life was observed up to the end of follow up. No significant side-effects were recorded. Our study underlines the efficacy and the safety of this novel GMA adsorber device; a prospective randomized clinical trial with adequate sample size should be performed.

Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis.

AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis. METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn(®) granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as (Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement (PUCAI decrease of 20 < 35), Small Improvement (PUCAI decrease of 10 < 20) or No change (PUCAI decrease of < 10). RESULTS: Twenty-five patients (mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set (ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol (PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients (45%); 5 out of 20 patients (25%) had Moderate Improvement and one patient (5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients (75%) showed Significant Improvement; and in two out of eight patients (25%) Moderate Improvement was recorded. The endoscopic activity index (EAI) decreased by 3 points on average. Seven (7) out of 21 (33%) patients in ITT and 4 out of 8 (50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12. CONCLUSION: Adacolumn(®) GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.

Ulcerative colitis with hepatitis B virus infection treated successfully by granulocyte monocyte apheresis.

Ulcerative colitis (UC) is a major type of idiopathic inflammatory bowel disease (IBD). Immunosuppressive therapies are used to treat IBD patients. Clinicians have strong concerns about using immunosuppressive therapies for IBD patients with hepatitis B virus (HBV) infection because aggressive immunosuppressive therapy can promote reactivation of HBV. For that reason, physicians hesitate to use steroids or other immunosuppressive drugs for IBD patients with HBV infection. Granulocyte monocyte apheresis (GMA) is a safe and effective therapy for UC patients. In Japan, a maximum of 11 sessions of GMA are allowed for moderate-to-severe, steroid-resistant UC patients. However, the effects of GMA on HBV remain unclear. This case report describes a 39-year-old man with active UC complicated by HBV infection. Although his symptoms improved with steroid treatment while under entecavir therapy, clinical remission could not be maintained after the steroid dosage was decreased, so GMA was started. After GMA initiation, the frequency of diarrhea decreased and his symptoms improved, and the steroid dosage could be decreased. During the course of GMA, the patient did not experience deterioration in his hepatitis and the HBV DNA level gradually decreased, although GMA itself did not affect the HBV DNA level during each session of GMA. Results show that GMA is a safe and efficacious strategy against UC complicated by HBV without affecting hepatitis because GMA had no remarkable effect on HBV activity. J. Clin. Apheresis 31:584-586, 2016. © 2015 Wiley Periodicals, Inc.

A longitudinal study of FDG-PET in Crohn disease patients receiving granulocyte/monocyte apheresis therapy.

BACKGROUND AIMS: Endoscopy is the gold standard for the diagnosis and follow-up of patients with Crohn disease (CD). However, a less invasive approach is now being sought for the management of these patients. The objective of this study was to examine whether (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) might be relevant for monitoring the disease activity in CD patients undergoing granulocyte/monocyte apheresis (GMA). METHODS: This study was conducted in 12 patients with CD who were receiving treatment with 10 once-a-week GMA sessions with the Adacolumn. The response to treatment was monitored by measuring standard laboratory variables, Crohn's Disease Activity Index (CDAI) score, International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) score, and regional and global bowel uptakes on FDG-PET. RESULTS: In 6 of the 12 patients, significant improvement of the CDAI was observed after the final session of GMA. The patients who showed clinical response to GMA had a decrease in the regional and global bowel uptakes on FDG-PET, whereas those who did not respond showed no change. In the patients who responded to the GMA, the decrease in regional bowel uptake on FDG-PET in each disease area of the same patient varied in parallel. There was a significant correlation between decrease in the global bowel uptake on FDG-PET and improvement of the CDAI and IOIBD scores. CONCLUSIONS: The longitudinal changes in FDG-PET uptakes are of potential clinical interest for assessing the regional and global bowel disease activity in CD patients undergoing GMA therapy.

Ulcerative colitis and granulocyte-monocyte-apheresis: safety and efficacy of maintenance therapy during pregnancy.

Inflammatory bowel disease characteristically affects young adults in their reproductive ages. Thus the medication used for the treatment of active disease should not compromise fertility and, also, should not have teratogenic effect on baby. A lot of data are available about effects of steroids, antibiotics, and mesalazine but no data are available about safety and efficacy of granulocyte-monocyte-apheresis (GMA) during pregnancy. In this case report, the 37 year-old pregnant woman with chronically active and steroid dependent ulcerative colitis (UC), at risk of abortion, refused more aggressive pharmacological therapeutic options and gave the informed consent to GMA. To minimize symptoms and the risk of severe clinical relapse, a maintenance GMA treatment was performed throughout pregnancy. The course of pregnancy was uneventful with no side effects; the mother and the baby were all healthy and well at the delivery.

Adsorptive granulocyte/monocyte apheresis for the maintenance of remission in patients with ulcerative colitis: a prospective randomized, double blind, sham-controlled clinical trial.

BACKGROUND/AIMS: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. METHODS: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. RESULTS: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. CONCLUSIONS: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy.

Adsorptive Granulocyte/Monocyte Apheresis for the Maintenance of Remission in Patients with Ulcerative Colitis: A Prospective Randomized, Double Blind, Sham-Controlled Clinical Trial

BACKGROUND/AIMS: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. METHODS: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. RESULTS: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. CONCLUSIONS: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy.