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Efficacy of apheresis as maintenance therapy for patients with ulcerative colitis in an open-label prospective multicenter randomised controlled trial
Naganuma M, Yokoyama Y, Motoya S, Watanabe K, Sawada K, Hirai F, Yamamoto T, Hanai H, Omori T, Kanai T, et al
Journal of gastroenterology. 2019
Abstract
BACKGROUND Apheresis therapy involves the selective removal of leukocytes and is used to induce remission in ulcerative colitis (UC) patients. The aim of this study was to demonstrate the efficacy and safety of apheresis therapy for maintaining UC remission. METHODS We conducted a multicenter, prospective, randomised-control trial of patients with remitting UC induced by granulocyte and monocyte adsorption apheresis or leukocytapheresis. Patients were randomly assigned to the apheresis group (twice per month for 12 months) or the control group (no apheresis treatment) using a 1:1 allocation ratio. The primary endpoint was the rate of cumulative clinical remission (Mayo score ≤ 2) at 12 months. The secondary endpoints were the rates of clinical remission, endoscopic remission, and complete endoscopic remission at 12 months. RESULTS Between March 2013 and March 2017, 164 patients were enrolled. The cumulative remission rate at 12 months was 46.6% in the apheresis group and 36.4% in the control group (p = 0.1621). The rate of endoscopic remission at 12 months was significantly higher in the apheresis group than in the control group (42.5% vs. 25.9%) p = 0.0480). The rate of clinical remission (47.5% vs.32.1%, p = 0.0540) and complete endoscopic remission (33.8% vs.19.8%, p = 0.0513) tended to be higher in the apheresis than in the control group; however, the difference was not significant. No severe adverse events were observed in either group. CONCLUSIONS Apheresis was well tolerated as maintenance therapy for UC although the cumulative clinical remission rate at 12 months was comparable between the apheresis and control groups.
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An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn's disease
Yoshimura N, Yokoyama Y, Matsuoka K, Takahashi H, Iwakiri R, Yamamoto T, Nakagawa T, Fukuchi T, Motoya S, Kunisaki R, et al
BMC Gastroenterology. 2015;15((1)):163.
Abstract
BACKGROUND Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn's disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD. METHODS In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level). RESULTS Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 +/- 5.3 days in the weekly GMA and 21.7 +/- 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/muL to 6950/muL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern. CONCLUSIONS In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.
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An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment
Sakuraba A, Motoya S, Watanabe K, Nishishita M, Kanke K, Matsui T, Suzuki Y, Oshima T, Kunisaki R, Matsumoto T, et al
The American Journal of Gastroenterology. 2009;104((12):):2990-5.
Abstract
OBJECTIVES Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active ulcerative colitis (UC). However, with routine weekly treatment, it may take several weeks to achieve remission, and to date, the efficacy of a more frequent treatment schedule remains unknown. The aim of this study was to assess the clinical efficacy and safety of intensive GMA treatment in patients with active UC. METHODS This was an open-label, prospective, randomized multicenter study to compare an intensive, two GMA sessions per week, with the routine, one GMA session per week. A total of 163 patients with mild-to-moderately active UC were randomly assigned to routine weekly treatment or intensive treatment. The maximum number of sessions of GMA permitted was 10. However, when patients achieved remission, GMA was discontinued. Remission rate at the end of the study, time to remission, and adverse events were assessed in both groups. RESULTS Of the 163 patients, 149 were available for efficacy analysis as per protocol, 76 were in weekly GMA, and 73 were in intensive GMA. At the end of the study period, clinical remission was achieved in 41 of 76 patients (54. 0%) in weekly GMA and in 52 of 73 patients (71. 2%) in intensive GMA (P=0. 029). The mean time to remission was 28. 1+/-16. 9 days in the weekly GMA treatment group and 14. 9+/-9. 5 days in the intensive GMA group (P<0. 0001). Intensive GMA was well tolerated without GMA-related serious adverse side effects. CONCLUSIONS Intensive GMA in patients with active UC seems to be more efficacious than weekly treatment, and significantly reduced the patients' morbidity time without increasing the incidence of side effects.
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A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis
Sands BE, Sandborn WJ, Feagan B, Löfberg R, Hibi T, Wang T, Gustofson LM, Wong CJ, Vandervoort MK, Hanauer S, et al
Gastroenterology. 2008;135((2):):400-9.
Abstract
BACKGROUND & AIMS Activated granulocytes and monocytes/macrophages are implicated in the pathogenesis of ulcerative colitis. Open-label studies and clinical experience in Japan and Europe have suggested that granulocyte/monocyte apheresis is safe and effective in treating ulcerative colitis. METHODS We evaluated the efficacy of granulocyte/monocyte apheresis in a randomized, double-blind, sham-controlled trial in patients with active moderate-to-severe ulcerative colitis (Mayo score 6-11) in community-based and tertiary care centers. As intervention, we used granulocyte/monocyte apheresis with the Adacolumn Apheresis System (JIMRO, Ltd, Takasaki, Japan) or sham apheresis in a 2:1 ratio for 9 weeks of treatment in a North American pivotal study (N = 168) and in a smaller, companion study of identical design conducted in Europe and Japan (N = 47). RESULTS In the pivotal study, clinical remission rates (Mayo score 0-2, with scores of 0 on rectal bleeding and 0 or 1 on endoscopic examination) were 17% and 11% for the granulocyte/monocyte apheresis (n = 112)- and sham-treatment groups, respectively (n = 56; P = . 361). Clinical response (Mayo score reduction of ≥3 points from baseline) was observed in 44% and 39% of patients, respectively (P = . 620). Similar changes were observed for the apheresis- and sham-treatment groups for endoscopic remission and response, and changes in Mayo and quality-of-life scores. The companion study and pooled data from both studies also yielded similar results. CONCLUSIONS In this study, granulocyte/monocyte apheresis was well tolerated but did not demonstrate efficacy for induction of clinical remission or response in patients with moderate-to-severe ulcerative colitis.
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5.
A pilot open-labeled prospective randomized study between weekly and intensive treatment of granulocyte and monocyte adsorption apheresis for active ulcerative colitis
Sakuraba A, Sato T, Naganuma M, Morohoshi Y, Matsuoka K, Inoue N, Takaishi H, Ogata H, Iwao Y, Hibi T
Journal of Gastroenterology. 2008;43((1):):51-6.
Abstract
BACKGROUND Recently, granulocyte and monocyte adsorption apheresis (GMA) has been shown to be effective for active ulcerative colitis (UC). Its original weekly treatment schedule is effective in about 70% of active UC. However, it takes about 3-4 weeks to achieve remission, and the efficacy of a more frequent treatment schedule has not been elucidated yet. We performed a pilot open-labeled prospective, randomized, controlled study comparing weekly and an intensive treatment schedule with three treatment sessions per week in the first 2 weeks. METHODS Thirty active UC patients with moderate disease activity were prospectively and randomly assigned to receive the original or the intensive treatment schedule for a total of ten sessions. The proportion of the patients achieving remission and the time to achieve remission among them was compared between the two groups. The incidences of adverse effects were also compared between the two groups. RESULTS The rate of inducing remission in the original and intensive treatment group was 66. 7% and 80%, respectively (P = 0. 25, NS). The time to achieve remission was 27. 2 days in the original group and 10. 7 days in the intensive group (P = 0. 04). Adverse effects were observed in two patients in each groups (NS). CONCLUSIONS Intensive treatment with GMA is an efficacious and safe treatment for active UC. Because it induces rapid remission, it may be a more ideal treatment regimen than the conventional weekly treatment.
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6.
Multicenter randomized controlled trial for the treatment of ulcerative colitis with a leukocytapheresis column
Sawada K, Muto T, Shimoyama T, Satomi M, Sawada T, Nagawa H, Hiwatashi N, Asakura H, Hibi T
Current Pharmaceutical Design. 2003;9((4):):307-21.
Abstract
The administration of steroids is not always effective for the treatment of ulcerative colitis (UC). Their long-term use often causes adverse effects which sometimes result in their stoppage and acute exacerbation. Therefore, an alternative treatment is necessary in order to decrease steroid dosage and avoid the clinical problems associated with steroids. Methods The effectiveness and adverse effects of a leukocytapheresis (LCAP) were investigated in a controlled multicenter trial with randomized assignment of 76 active-stage UC patients in two groups. In the LCAP group (39 patients), LCAP weekly for 5 weeks as an intensive therapy was added to the on-going drug therapy, while steroids were maintained but not increased, and then LCAP was gradually reduced to once every 4 weeks as a maintenance therapy. In the high dose prednisolone (h-PSL) group (37 patients), PSL was added or increased 30 approximately 40 mg/day for moderately severe and 60 approximately 80 mg/day for severe patients and then gradually tapered. Findings The LCAP group showed a significantly higher effectiveness (74% vs. 38%; p=0. 005) and lower incidence of adverse effects (24% vs. 68%; p<0. 001). The patients were able to continue the trial for a longer period in the LCAP group than the h-PSL group (p=0. 012). Clinical activity and endoscopic indexes showed the LCAP group had better improvements than the h-PSL group. Interpretation The results of the trial show that LCAP permits a reduction in total PSL dosage and is more effective and safer than high-dose PSL administration for intensive therapy, and LCAP may maintain remission longer than PSL.