Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial.
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ABSTRACT: Background
Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids.Methods
We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks.Results
The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing.Conclusions
GMA shows effectiveness in inducing remission in UC patients not receiving steroid.
SUBMITTER: Kakimoto K
PROVIDER: S-EPMC7797742 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, double-blind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs 145 000 ($1 300). However, if this treatment prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.
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Project description:AimTo investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.MethodsThe 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).ResultsTwenty-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.ConclusionAdacolumn(®) 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.
| S-EPMC4853697 | biostudies-literature
Project description:Background:Granulocyte-monocyte apheresis has been proposed for the treatment of ulcerative colitis, although it is limited by costs and variability of results. Aim:To assess effectiveness of granulocyte-monocyte apheresis in patients with steroid-dependent, azathioprine-intolerant/resistant moderate ulcerative colitis. Methods:Consecutive patients fulfilling inclusion criteria were prospectively enrolled, treated by apheresis, and followed up for 12 months. The primary end point of the study was steroid-free clinical remission at 12 months, with no need for biologic therapy or surgery. Results:From January to December 2013, 33 patients were enrolled. After one year of follow-up, 12 (36%) patients had clinical remission, were steroid-free, and had no need for biological therapy or surgery; 3 (9%) cases showed a clinical response (but not clinical remission). Moreover, 12 (36%) patients required biologic therapy, 4 (12%) underwent colectomy, and in the other 2 (6%) a reduction, but not withdrawal, of steroid dose was achieved. Conclusions:Our study shows that a standard course of granulocyte-monocyte apheresis is associated with a 36% steroid-free clinical remission in patients with steroid-dependent, azathioprine-intolerant or resistant moderate ulcerative colitis. Apheresis might represent an alternative to biologic therapy or surgery in this specific subgroup of patients. This trial is registered with Clinicaltrial.gov NCT03189888.
| S-EPMC5748298 | biostudies-literature
Project description:ObjectiveThe goal of treatment in ulcerative colitis (UC) is to induce and maintain remission. The addition of granulocyte and monocyte apheresis (GMA) to conventional therapy may be a promising therapeutic alternative. In this meta-analysis, we aimed to assess the efficacy and safety profile of GMA as an adjunctive therapy.DesignSystematic review and meta-analysis.MethodsWe searched four databases (MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials) for randomised or minimised controlled trials which discussed the impact of additional GMA therapy on clinical remission induction and clinical remission maintenance compared with conventional therapy alone. Primary outcomes were clinical remission induction and maintenance, secondary outcomes were adverse events (AEs) and steroid-sparing effect. ORs with 95% CIs were calculated. Trial Sequential Analyses were performed to adjusts for the risk of random errors in meta-analyses.ResultsA total of 11 studies were eligible for meta-analysis. GMA was clearly demonstrated to induce and maintain clinical remission more effectively than conventional therapy alone (598 patients: OR: 1.93, 95% CI 1.28 to 2.91, p=0.002, I2=0.0% for induction; 71 patients: OR: 8.34, 95% CI 2.64 to 26.32, p<0.001, I2=0.0% for maintenance). There was no statistically significant difference in the number of AEs (OR: 0.27, 95% CI 0.05 to 1.50, p=0.135, I2=84.2%).ConclusionGMA appears to be more effective as an adjunctive treatment in inducing and maintaining remission in patients with UC than conventional therapy alone.Prospero registration numberCRD42019134050.
| S-EPMC8137160 | biostudies-literature
Project description:AimsSARS-CoV-2 causes systemic immune dysfunction, leading to severe respiratory dysfunction and multiorgan dysfunction. Granulocyte and monocyte adsorptive apheresis (GMA) therapy is designed to regulate an excessive inflammatory response and has been proposed as a potential therapeutic strategy for coronavirus disease 2019 (COVID-19). We aimed to investigate a targeted subset of granulocytes and monocytes to be removed after GMA therapy in patients with severe COVID-19 infection.MethodsWe established an ex vivo experimental system to study the effects of GMA. Blood samples were collected into EDTA-treated tubes and a mixture of blood samples and cellulose acetate beads was used in GMA. After GMA, blood samples were removed, and the granulocyte and monocyte subtypes before and after GMA were determined by CyTOF mass cytometry. To analyze mass cytometry data with a self-organizing map, hierarchical clustering was used to determine the appropriate number of metaclusters from t-distributed stochastic neighbor embedding.ResultsWe included seven patients with severe COVID-19 and four age- and sex-matched volunteers. Granulocyte subsets removed by GMA strongly expressed CD11b, CD16, and CD66b, and weakly expressed CD11c, consistent with mature and activated neutrophils. Monocyte subsets strongly expressed CD14, weakly expressed CD33 and CD45RO, and did not express CD16. These subsets were indicated to promote the release of inflammatory cytokines and activate T cells.ConclusionsThe identification of the granulocyte and monocyte subsets removed after GMA in patients with severe COVID-19 may help explain the potential mechanism underlying the effectiveness of GMA in COVID-19 and other inflammatory diseases.
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Project description:BACKGROUND:The available information on granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) under special situations remains unclear. We conducted a retrospective, multicentre cohort study to evaluate the safety and effectiveness of GMA in patients with IBD under special situations. METHODS:This study included patients with ulcerative colitis (UC) or Crohn's disease who had at least one special situation feature and who had received GMA between November 2013 and March 2017. The incidence of adverse events (AEs) was compared in relation to the special situation, and patient background factors related to an AE were identified. For patients with UC, clinical remission was defined as a partial Mayo score of ≤2. RESULTS:A total of 437 patients were included in this study. The incidence of AEs among the elderly patients (11.2%) was similar in all patients (11.4%), whereas the incidences of AEs in patients on multiple immunosuppressant medications (15.2%), patients with anaemia (18.1%) and paediatric/adolescent patients (18.9%) were higher than that in all patients (11.4%). In multivariate analysis, anaemia and concomitant immunosuppressant medications were independently associated with the incidence of AEs. Clinical remission was achieved in 46.4% of the patients with UC. CONCLUSIONS:The incidence of AEs in the elderly patients was not higher than that in all patients, whereas the incidence of AE was higher in patients with anaemia and those on multiple immunosuppressant medications than that in all patients. GMA is a safe treatment option in elderly patients with IBD.
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Project description:Background and aimsPatients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup.MethodsThis single-arm, open-label, multicentre trial [ART] was conducted at 18 centres across the UK, France, and Germany. Eligible patients were 18-75 years old with moderate-to-severe, steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics. Patients received ≥ 5 weekly apheresis sessions with Adacolumn. The primary endpoint was clinical remission rate [clinical activity index ≤ 4] at Week 12.ResultsIn all, 86 patients were enrolled. At Week 12, 33/84 [39.3%] of patients in the intention-to-treat population achieved clinical remission, with 47/84 [56.0%] achieving a clinical response [clinical activity index reduction of ≥ 3]. Clinical remission was achieved in 30.0% of patients with previous immunosuppressant and biologic failure; steroid-free clinical remission and response were observed in 22.6% and 35.7% of these patients, respectively. Quality of life [Short Health Scale] significantly improved at Week 12 [p < 0.0001]. The majority of adverse events were of mild/moderate intensity.ConclusionsAt Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgroup.
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Project description:In the last few years, a new non-pharmacological treatment, termed apheresis, has been developed to lessen the burden of ulcerative colitis (UC). Several methods can be used to establish treatment recommendations, but over the last decade an informal collaboration group of guideline developers, methodologists, and clinicians has developed a more sensible and transparent approach known as the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). GRADE has mainly been used in clinical practice guidelines and systematic reviews. The aim of the present study is to describe the use of this approach in the development of recommendations for a new health technology, and to analyse the strengths, weaknesses, opportunities, and threats found when doing so.A systematic review of the use of apheresis for UC treatment was performed in June 2004 and updated in May 2008. Two related clinical questions were selected, the outcomes of interest defined, and the quality of the evidence assessed. Finally, the overall quality of each question was taken into account to formulate recommendations following the GRADE approach. To evaluate this experience, a SWOT (strengths, weaknesses, opportunities and threats) analysis was performed to enable a comparison with our previous experience with the SIGN (Scottish Intercollegiate Guidelines Network) method.Application of the GRADE approach allowed recommendations to be formulated and the method to be clarified and made more explicit and transparent. Two weak recommendations were proposed to answer to the formulated questions. Some challenges, such as the limited number of studies found for the new technology and the difficulties encountered when searching for the results for the selected outcomes, none of which are specific to GRADE, were identified. GRADE was considered to be a more time-consuming method, although it has the advantage of taking into account patient values when defining and grading the relevant outcomes, thereby avoiding any influence from literature precedents, which could be considered to be a strength of this method.The GRADE approach could be appropriate for making the recommendation development process for Health Technology Assessment (HTA) reports more explicit, especially with regard to new technologies.
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