scholarly journals DOP04 Matching between donors and patients in faecal microbiota transplantation is important for long-term maintenance on ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S043-S044 ◽  
Author(s):  
D Ishikawa ◽  
K Okahara ◽  
M Takahashi ◽  
K Haga ◽  
K Nomura ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Rank Test ◽  
Age Difference ◽  
Faecal Microbiota ◽  
Maintenance Rate ◽  
Log Rank Test ◽  
Short And Long Term ◽  
Term Maintenance

Abstract Background We previously demonstrated that fresh-faecal microbiota transplantation (FMT) following triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); A-FMT] for ulcerative colitis (UC) patients induced changes in the phylum Bacteroidetes, which constitutes a critical factor correlated with clinical responses. Here, we analyse the short- and long-term efficacy of A-FMT comparing to AFM monotherapy, and we explore the concept of a beneficial donor for long-term maintenance. Methods This prospective and non-randomised control study was conducted from July 2014 to March 2017. Eligible patients were at least 20 years of age, with a diagnosis of active UC which were required a Lichtiger’s clinical activity index (CAI) of 5 or more, or with an endoscopic Mayo score of 1 or more. Patients’ spouses or relatives in the family were selected as donors. AFM was administered to patients with UC for 2 weeks, and up to 2 days before fresh FMT. Clinical response was defined as a decrease of CAI of 3 points or more, and remission was defined as 3 points or less. Maintenance of efficacy was defined as no exacerbation of CAI and no intensification of treatments. Results Seventy-nine patients completed protocol (A-FMT; n = 47, mono-AFM; n = 32). At 4 weeks after treatment, clinical response and remission were observed in 31 and 19 patients (65.9%, 40.4%) in A-FMT, which higher than in mono-AFM respectively (56.2%, 18.7%). The maintenance rate of clinical responder was shown to be significantly higher in A-FMT than in AFM at 12 months and 24 months after treatment (A-FMT vs. mono-AFM, p = 0.046 and 0.034, Wilcoxon test). In A-FMT, in case that the age difference between donor and patient is more than 11 years, maintenance rate was significantly lower than 0–10 age difference in A-FMT (≥11 vs. 0–10, n = 14, 16; p = 0.004 and p = 0.003, log-rank test). Siblings relationship has a significantly higher maintenance rate compared with parent–child relationship (Siblings vs. parent–child; n = 7, 13; p = 0.009 and p = 0.006, log-rank test). Conclusion A-FMT exhibited reassuring clinical outcomes in terms of short and long term. This is the first report of FMT to reveal the importance of matching between donors and patients for long-term maintenance on UC.

scholarly journals Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation

2020 ◽  
Vol 9 (6) ◽  
pp. 1650
Author(s):  
Koki Okahara ◽  
Dai Ishikawa ◽  
Kei Nomura ◽  
Shoko Ito ◽  
Keiichi Haga ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Post Treatment ◽  
Age Difference ◽  
Maintenance Rate ◽  
Term Efficacy ◽  
Term Maintenance

We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent–child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen.

25 DONOR SELECTION OF FECAL MICROBIOTA TRANSPLANTATION IS IMPORTANT TO LONG-TERM MAINTENANCE OF ULCERATIVE COLITIS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S36-S36
Author(s):  
Koki Okahara ◽  
Dai Ishikawa ◽  
Kei Nomura ◽  
Shoko Ito ◽  
Keiichi Haga ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Donor Selection ◽  
Age Difference ◽  
Maintenance Rate ◽  
Term Maintenance ◽  
Parent Child

Abstract Background Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for various disease. However, the therapeutic mechanism is still unclear. We previously demonstrated that fresh-fecal microbiota transplantation following triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); A-FMT] for ulcerative colitis (UC) patients induced changes in the phylum Bacteroidetes, which constitutes a critical factor correlated with clinical responses. Here, we analyzed microbiota to examine the beneficial species, and observed long-term course (12 months) of the patients who treated with AFM and A-FMT. Moreover, we explore the concept of best donor for FMT success. Methods This prospective and non-randomized controlled study was conducted from July 2014 to March 2017 at Juntendo University Hospital. Eligible patients were at least 20 years of age, with a diagnosis of active UC which were required a Lichtiger’s clinical activity index (CAI) of 5 or more, or with an endoscopic Mayo score of 1 or more. Patients’ spouses or relatives in the family were selected as donors. AFM was administered to patients with UC for 2 weeks, and up to 2 days before fresh FMT. Clinical response was defined as a decrease of CAI of 3 points or more, and remission was defined as 3 points or less. Maintenance of efficacy was defined as no exacerbation of CAI and no intensification of treatments. Results Seventy-nine patients completed protocol (A-FMT; n = 47, mono-AFM; n = 32). At 4 weeks after treatment, clinical response and remission were observed in 31 and 19 patients (65.9%, 40.4%) in A-FMT, which higher than in mono-AFM respectively (56.2%, 18.7%). The maintenance rate of clinical responder was shown to be significantly higher in A-FMT than in AFM at 12 months after treatment (A-FMT vs mono-AFM, n = 13, 10; P = 0.046). Furthermore, in case that the age difference between donor and patient is more than 11 years, maintenance rate was significantly lower than 0–10 age difference in A-FMT (≧11 vs 0–10, n = 14, 16; P = 0.004). Siblings relationship has a significantly higher maintenance rate compared to parent–child relationship (Siblings vs parent-child; n = 7, 13; P = 0.009). An analysis of some cases in which the microbiota was followed for 24 months revealed a tendency that some bacterial species such as Bacteroides dorei and Bacteroides uniformis maintained their effects. Conclusion A-FMT exhibited reassuring clinical outcomes in terms of both short and long term. This is the first report of FMT to reveal importance of donor selection for long-term maintenance for UC.

scholarly journals DOP07 Long-term results of 4.5 years of faecal microbiota transplantation for treatment of refractory ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S045-S045
Author(s):  
A Uygun ◽  
M F Karakaya ◽  
H Erdal ◽  
G Celebi ◽  
Y S Sakin ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Protocol Analysis ◽  
Long Term Results ◽  
Faecal Microbiota ◽  
Intention To Treat ◽  
Tnf Α ◽  
Treat Analysis

Abstract Background Faecal microbiota transplantation (FMT) provides replacement of pathogenic bacteria with more favourable microbiomes in recipients with dysbiosis. The aim of the present study was to prospectively investigate the efficacy of FMT by assessing the clinical and endoscopic response in patients with ulcerative colitis (UC) who had failed anti-inflammatory, immunosuppressive and TNF-α inhibitors (Infliximab, Adalimumab, Vedolizumab) therapy. Methods In this prospective and uncontrolled study, 116 patients with UC were enrolled. All medications except mesalazine were discontinued 1 week before FMT. Colonoscopy was performed both before and after FMT. To assess the efficacy of FMT, Mayo scores were calculated at weeks 0, 24 and 48. A total of 400–600 ml of extracted fresh faecal suspension was administered into the 20 to 30  cm of terminal ileum of recipients. Results After 4.5 years of FMT experience with 116 patients, who have completed their 6 months after 236 procedures of FMT for treatment of UC, 42 of the 116 patients showed full clinical response (100% clinical + laboratory + endoscopically full response) (per-protocol analysis 37.1%), (intention-to-treat analysis 36.2%) at Week 48 and 33 of the 116 patients achieved clinical and endoscopic remission (laboratory 70%, clinically and endoscopically 50–75% improvement) (per-protocol analysis 29.2%), (intention-to-treat analysis 28.4%) at Week 48. Thirty-eight of the 116 patients were accepted as nonresponders at the end of Week 48 (per-protocol analysis 29.2%), (intention-to-treat analysis 32.7%) and 3 patients (2.5%) were lost to follow-up. There was no significant difference among donors concerning both the rate of clinical remission and clinical response. At 4.5 years, serious side effects were observed on 2 patients, 1 colon perforation and 1 toxic megacolon; both were directed to surgery. In 48 weeks’ follow-up, 31 patients (26.7%) experienced mild adverse events after FMT, such as elevated white blood cell counts and ESR, nausea, abdominal pain and high fever, all were managed conservatively. Conclusion FMT could be considered as a promising rescue treatment modality before surgery in patients with refractory UC. Our research is the first in the world for the treatment of UC resistant to medical treatment before surgery. Also, it is the first research to show the long-term results of FMT. FMT appears to be significantly safer and more tolerable than the immunosuppressive and TNF-α inhibitors therapy in patients with UC.

scholarly journals Rituximab Maintenance Treatment for a Maximum of 5 Years in Follicular Lymphoma: Final Results of the Randomized Phase III Trial SAKK 35/03

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1601-1601 ◽  
Author(s):  
Christian Taverna ◽  
Giovanni Martinelli ◽  
Felicitas Hitz ◽  
Walter Mingrone ◽  
Thomas Pabst ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Iii ◽  
Rank Test ◽  
Short Term ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
Log Rank Test ◽  
Term Maintenance

Abstract Background: Follicular lymphoma is usually a disase with a prolonged course and a chemotherapy-free regimen might be a favourable treatment strategy. SAKK 35/03 investigated two different durations of rituximab maintenance (5 years vs. 6 months) in patients with follicular lymphoma after induction with 4 weekly doses of rituximab monotherapy. With a median follow-up of 6.4 years we were not able to show a benefit with long-term rituximab maintenance up to five years in event-free survival (EFS) or overall survival (OS ). Here we report the final results with a median follow-up of 10 years. Methods: 270 patients (median age 57 years: range 25-82) with untreated, relapsed, stable or chemotherapy resistant follicular lymphoma were treated with 4 doses of rituximab monotherapy in weekly intervals (375 mg/m²). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of five years or until disease progression or unacceptable toxicity). The primary endpoint was EFS . Progression-free survival (PFS), OS, and toxicity were secondary endpoints. Comparisons between the two treatment arms were performed using the log-rank test for survival endpoints. Results: 165 patients were randomly assigned to short-term (n=82) or long-term (n=83) maintenance. At a median follow-up period of 10 years, the median EFS is 3.4 years (95% CI 2.1-5.5) in the short-term arm and 5.3 years (95% CI 3.5-7.5) in the long-term arm. Using the pre-specified log-rank test this difference is statistically not significant (p=0.39 ). There is no significant difference in PFS and OS. Median OS in the short-term arm is 11.0 years (95% CI 11.0, NA ) and not reached in the long-term arm (p=0.80). The incidence of subsequent cancers increased in both arms over time, nine patients developed a subsequent cancer in the short-term maintenance arm and 10 in the long-term maintenance arm. There was no major additional toxicity with longer follow-up. Conclusions : Even with a long follow-up of 10 years we were not able to show a significant benefit of long-term compared to short-term rituximab maintenance in EFS, PFS and OS. Treatment strategies and study designs need to take these results into consideration in order to guarantee optimal medical and scientific results. Disclosures Zucca: Celltrion: Consultancy; AstraZeneca: Consultancy. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Strategies in maintenance for patients receiving long-term therapy (SIMPLE): A study of MMX mesalamine for the long-term maintenance of quiescent ulcerative colitis*

2012 ◽  
Vol 18 (6) ◽  
pp. 1026-1033 ◽  
Author(s):  
Sunanda Kane ◽  
Seymour Katz ◽  
Mazen M. Jamal ◽  
Michael Safdi ◽  
Ben Dolin ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Term Therapy ◽  
Long Term Therapy ◽  
Term Maintenance

scholarly journals A Comparison of Short- and Long-Term Therapeutic Outcomes of Infliximab- versus Tacrolimus-Based Strategies for Steroid-Refractory Ulcerative Colitis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Katsuya Endo ◽  
Motoyuki Onodera ◽  
Hisashi Shiga ◽  
Masatake Kuroha ◽  
Tomoya Kimura ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Therapeutic Efficacy ◽  
Maintenance Treatment ◽  
Remission Rate ◽  
Rank Test ◽  
Clinical Response Rate ◽  
Therapeutic Outcomes ◽  
Significant Difference ◽  
Steroid Refractory

Background/Aims. Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC). Although some studies have compared the efficacy of infliximab (IFX) and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac). This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC.Methods. Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX(n=48)or Tac(n=47)in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups.Results. There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group (p<0.001; log-rank test). The proportions of serious adverse events did not differ between the groups.Conclusion.The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment.

scholarly journals The relationship of the prolonged PR interval with the long-term survival in patients with heart failure undergoing cardiac resynchronization therapy

2020 ◽  
Vol 25 (1) ◽  
pp. 33-38
Author(s):  
A. M. Soldatova ◽  
V. A. Kuznetsov ◽  
T. P. Gizatulina ◽  
L. M. Malishevsky ◽  
S. M. Dyachkov
Keyword(s):  
Cardiac Resynchronization ◽  
Rank Test ◽  
Term Survival ◽  
Log Rank Test ◽  
Group I ◽  
Pr Interval ◽  
Qrs Duration ◽  
Group Ii ◽  
The Relationship

Aim. To assess the relationship between the prolonged PR interval (≥200 ms) and the long-term survival of patients undergoing cardiac resynchronization therapy (CRT).Material and methods. A total of 85 patients (mean age — 55,1Ѓ}9,9 years; men — 81,2%) with NYHA class II-IV heart failure (HF) were examined. The mean follow-up was 34,0Ѓ}21,2 months. Patients with PR<200 ms (n=52) made up group I, with PR≥200 ms (n=33) — group II. Then the patients were divided into subgroups depending on the QRS duration: ≥150 ms (n=33 in group I and n=14 in group II, respectively) <150 ms (n=19 in group I and n=19 in group II, respectively).Results. In patients of group II, a history of myocardial infarction (MI) was more often registered (p=0,005), left ventricular ejection fraction (LVEF) was lower (p=0,032). In a multivariate analysis, MI (OR 3,217; CI 95% 1,188-8,712; p=0,022) and LVEF value (OR 0,869; CI 95% 0,780-0,968; p=0,011) had a significant relationship with the PR interval prolongation (≥200 ms). The survival of patients of group I was 59,6%, group II — 18,2% (Log-rank test p<0,001). According to Cox regression model, the initial left ventricle end-systolic volume (OR 1,012; 95% CI 1,006-1,017; p<0,001), inferior wall MI (OR 1,690; 95% CI 1,131-2,527; p=0,011) and PR interval ≥200 ms (OR 2,179; 95% CI 1,213–3,915; p=0,009) were associated with long-term mortality. In patients with PR≥200 ms, survival rate was low, regardless of the QRS duration (21,4% in patients with QRS≥150 ms, 15,8% in patients with QRS<150 ms; Log-rank test p=0,698) In patients with PR<200 ms, the survival rate of patients with QRS≥150 ms was 72,7%, and for patients with QRS<150 ms — 36,8% (Log-rank test p=0,031).Conclusion. In HF patients, PR interval prolongation (≥200 ms) is associated with long-term mortality increase. The highest survival rates were observed in patients with PR<200 ms and QRS≥150 ms. In patients with QRS≥150 ms, the presence of PR≥200 ms should be considered as an additional criterion for CRT.

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