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Background: Infliximab (IFX) is effective for remission induction and maintenance of Crohn's disease (CD). This trial assessed the efficacy of scheduled maintenance IFX monotherapy to prevent postoperative CD recurrence. Methods: Thirty-one CD patients who had ileocolic resection within the past 4 weeks were randomly assigned to scheduled IFX at 5 mg/kg intravenously every 8 weeks for 36 months (n = 15) or without IFX (control, n = 16). All patients were treated without immunomodulator or corticosteroid following surgery. The primary and secondary endpoints were remission rates at 12 and 36 months, defined as CD Activity Index (CDAI) ≤150, an International Organization for the Study of Inflammatory Bowel Disease (IOIBD) score

Background: Leukocytapheresis (LCAP) is used as an adjunct therapy for patients with active ulcerative colitis (UC). Although, LCAP is routinely performed at 3,000 mL per session, we were interested to see that if this can be replaced with bodyweight (BW) adjusted volume. Methods: In an open label prospective trial, the clinical response to BW adjusted LCAP (BWA-LCAP) was evaluated in 14 patients with active UC. Fourteen demography matched UC patients who had been treated with the routine 3,000 mL LCAP were randomly sampled from our database as a control group. All patients were given 10 weekly LCAP sessions. In the BWA-LCAP group, the processed blood volume (PBV) was set at 30 mL/kg × BW/session. Baseline demographic measures were not significantly different between the two groups. Results: The average PBV in the BWA-LCAP group was 1971.0 ± 330.0 mL, range 1,020–2,460. In both groups, the average UC clinical disease activity index, the endoscopic index, and the concomitant prednisolone dosage were significantly and equally reduced during the course of 10 LCAP. Accordingly, at the end of the trial, no significant difference was seen in any outcome measure between the two groups. However, a significantly higher incidence of adverse event (AE) was observed in the routine 3,000 mL LCAP group as compared with the BWA-LCAP group (P < 0.01). Conclusions: The outcomes of this investigation showed that the therapeutic efficacy of LCAP based on 30 mL/kg × BW is similar to the routine 3,000 mL per session LCAP. However, BWA-LCAP should be favored if one is to see the full potential of LCAP without AE. © 2011 Wiley Periodicals, Inc.

In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved treatment option in patients with active Crohn's disease (CD). However, there is inadequate knowledge regarding the mechanism(s) of therapeutic effects of this non-pharmacologic treatment strategy. Further, recently we have been interested in the regulatory T-cell (Treg) profile which has an essential immunoregulatory function. Thirteen CD patients were treated with a single GMA session. The mean CD activity index (CDAI) and duration of CD were 218.5 and 9.8 years, respectively. Eight healthy volunteers participated as a control group. From CD patients, whole blood was taken immediately before and after the GMA session directly from the GMA column inflow and outflow lines. Broad spectrum serum key cytokines and chemokines were measured by suspension-array and ELISA. At baseline, almost all assayed inflammatory cytokines were significantly elevated in CD patients. Treg-associated cytokines including IL-10 (P < 0.02) and transforming growth factor (TGF)-β1 (P < 0.03), were higher in the GMA column outflow vs. inflow. In contrast, the Th1/Th2 balance, defined as IFN-γ/IL-10 was lower during hemofiltration (P = 0.05), potentially due to an elevated IL-10 (P < 0.02) because an elevation of pro-inflammatory IFN-γ (Th1) was not observed at the GMA column outflow. A single GMA session had a significant impact on the Treg profile. Treg-related cytokines like IL-10 and TGF-β1 in the blood returning to the patients from the GMA column outflow were elevated, while pro-inflammatory cytokines like IFN-γ were not. This action of GMA is potentially very interesting in patients with immune disorders, like CD patients.

Granulocyte/monocyte adsorption (GMA) has been introduced as an adjunct intervention for active ulcerative colitis (UC) patients. The processed blood volume (PV) per GMA session is an important factor for its efficacy because depletion of elevated/activated myeloid leukocytes is its main action. Hitherto, this aspect of GMA has been largely ignored. Thirty-three patients were enrolled for remission induction therapy with five weekly GMA sessions at a standard PV of 1800 mL, regardless of patients' bodyweight (BW). The patients were divided into three groups: high (H)BW (≥ 65 kg, n = 11), 50 kg ≤ medium (M)BW < 65 kg (n = 12), and low (L)BW (≤ 50 kg, n = 10). UC clinical activity index (CAI) was according to Lichtiger, and the clinical efficacies were evaluated at both one week post 3(rd) GMA (Week 4) and one week post 5(th) GMA (Week 6). The average BW was 70.9 ± 6.2 kg in HBW, 55.8 ± 4.5 kg in MBW, and 46.8 ± 1.2 kg in LBW, indicating the mean PV/BW in the three groups being 25.6 ± 2.12, 32.5 ± 2.50, and 38.7 ± 1.0 (mL/kg, P < 0.05), respectively. The LBW group consisted of female patients only. Significant improvements of CAI were seen before treatment at either Week 4 or Week 6 in all groups. A significantly higher remission rate was achieved in the LBW (80.0%) vs. MBW (33.3%) or HBW (27.3%) at Week 6 (P < 0.03). According to this GMA evaluation, the lower-limit of optimum PV/kg should be higher than 38.7 mL/kg for its potential clinical efficacy to be significantly greater than the routine GMA method. Additional BW-oriented GMA studies in larger and gender controlled cohorts of patients should strengthen our findings.

Background: This is the first report on a case of Crohn's disease (CD), who was successfully maintained with a combination of infliximab (IFX) and selective depletion of granulocytes/monocytes by adsorption (GMA). Case: A 33-year-old female with CD activity index (CDAI) 294.2 responded to iv IFX (5mg/kg) administered at weeks 0, 2, and 6 in combination with 3000 mg/day oral 5-aminosalicylic acid (5-ASA; CDAI = 118). Then IFX at 8 week intervals was given as maintenance therapy. Two weeks before the 5th scheduled IFX, the patient worsened with an increase in stool frequency and a rise in CDAI. GMA was administered at weeks 5, 6, and 7 after her 6th iv IFX. Her CDAI decreased from 166.2 to 126.3 and 111.9 before 2nd and 3rd GMA sessions. She received her 7th iv IFX while the CDAI was 83.6. GMA course was repeated before 8th and 9th IFX. The patient remained in stable clinical and endoscopic remission without experiencing any serious side effect. After achieving mucosal healing, the patient decided to cease IFX therapy while continuing with GMA. Conclusions: IFX appears to induce and maintain remission of CD, but it may lose its efficacy after repeated administration. GMA is safe and by selectively depleting elevated/activated leukocytes may be a useful adjunct for IFX efficacy. J. Clin. Apheresis, 2010. © 2010 Wiley-Liss, Inc.

Granulocyte/monocyte adsorption (GMA) has been introduced as an adjunct intervention for active ulcerative colitis (UC) patients. The processed blood volume (PV) per GMA session is an important factor for its efficacy because depletion of elevated/activated myeloid leukocytes is its main action. Hitherto, this aspect of GMA has been largely ignored. Thirty-three patients were enrolled for remission induction therapy with five weekly GMA sessions at a standard PV of 1800 mL, regardless of patients' bodyweight (BW). The patients were divided into three groups: high (H)BW (≥ 65 kg, n = 11), 50 kg ≤ medium (M)BW65 kg (n = 12), and low (L)BW (≤ 50 kg, n = 10). UC clinical activity index (CAI) was according to Lichtiger, and the clinical efficacies were evaluated at both one week post 3(rd) GMA (Week 4) and one week post 5(th) GMA (Week 6). The average BW was 70.9 ± 6.2 kg in HBW, 55.8 ± 4.5 kg in MBW, and 46.8 ± 1.2 kg in LBW, indicating the mean PV/BW in the three groups being 25.6 ± 2.12, 32.5 ± 2.50, and 38.7 ± 1.0 (mL/kg, P0.05), respectively. The LBW group consisted of female patients only. Significant improvements of CAI were seen before treatment at either Week 4 or Week 6 in all groups. A significantly higher remission rate was achieved in the LBW (80.0%) vs. MBW (33.3%) or HBW (27.3%) at Week 6 (P0.03). According to this GMA evaluation, the lower-limit of optimum PV/kg should be higher than 38.7 mL/kg for its potential clinical efficacy to be significantly greater than the routine GMA method. Additional BW-oriented GMA studies in larger and gender controlled cohorts of patients should strengthen our findings.

In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved treatment option in patients with active Crohn's disease (CD). However, there is inadequate knowledge regarding the mechanism(s) of therapeutic effects of this non-pharmacologic treatment strategy. Further, recently we have been interested in the regulatory T-cell (Treg) profile which has an essential immunoregulatory function. Thirteen CD patients were treated with a single GMA session. The mean CD activity index (CDAI) and duration of CD were 218.5 and 9.8 years, respectively. Eight healthy volunteers participated as a control group. From CD patients, whole blood was taken immediately before and after the GMA session directly from the GMA column inflow and outflow lines. Broad spectrum serum key cytokines and chemokines were measured by suspension-array and ELISA. At baseline, almost all assayed inflammatory cytokines were significantly elevated in CD patients. Treg-associated cytokines including IL-10 (P0.02) and transforming growth factor (TGF)-β1 (P0.03), were higher in the GMA column outflow vs. inflow. In contrast, the Th1/Th2 balance, defined as IFN-γ/IL-10 was lower during hemofiltration (P = 0.05), potentially due to an elevated IL-10 (P0.02) because an elevation of pro-inflammatory IFN-γ (Th1) was not observed at the GMA column outflow. A single GMA session had a significant impact on the Treg profile. Treg-related cytokines like IL-10 and TGF-β1 in the blood returning to the patients from the GMA column outflow were elevated, while pro-inflammatory cytokines like IFN-γ were not. This action of GMA is potentially very interesting in patients with immune disorders, like CD patients.