1Department of Gastroenterology and Hepatobiliary Sciences, Fortis Memorial Research Institute, Gurugram, India
2Department of Histopathology, Fortis Memorial Research Institute, Gurugram, India
© Copyright 2022. Korean Association for the Study of Intestinal Diseases. All rights reserved.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Funding Source
The authors received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Author Contribution
Conceptualization: Seth AK. Data curation: Seth AK, Jain P. Formal analysis: Seth AK. Investigation: Seth AK, Jain P. Methodology: Seth AK. Project administration: Seth AK. Resources: Seth AK. Supervision: Seth AK. Validation: Seth AK. Visualization: Seth AK. Writing - original draft: Seth AK. Writing - review & editing: Seth AK. Approval of final manuscript: all author.
Non-Author Contribution
Authors thank Ms. Twinkle Singh (Fortis Organ Retrieval and Transplant, Gurugram, India) for data management and preparation of tables and figures, Mr. Sudhir Shekhawat (Fortis Healthcare Limited, New Delhi, India) for statistical analysis.
Characteristics | Value (n = 27) |
---|---|
Age (yr) | 33 ± 9 (18–50) |
Male sex | 18 (66) |
Disease duration (yr) | 4 ± 4 (1–18) |
Extent of disease at inclusion | |
E1, proctitis | 2 (7) |
E2, left sided | 10 (37) |
E3, pancolitis | 15 (56) |
Medications for 3 mo before inclusion | |
Glucocorticoids | 27 (100) |
Azathioprinea | 20 (74) |
Oral 5-aminosalicylates | 27 (100) |
Rectal 5-aminosalicylates | 7 (26) |
Biologicals experienced | 2 (7) |
Hemoglobin (g/L) | 12.0 (8.6–16.6) |
WBC count (× 103/mm3) | 7.2 (5.2–12.4) |
CRP (mg/L) | 5.6 (0.3–133.1) |
Peak Mayo score | 11 (9–12) |
Mayo score at inclusion | 5 (4–10) |
Variable |
Author (year) |
|||||
---|---|---|---|---|---|---|
Moayyedi et al. (2015) [10] | Rossen et al. (2015) [11] | Paramsothy et al. (2017) [12] | Crothers et al. (2018) [13] | Costello et al. (2019) [14] | Sood et al. (2019) [19] | |
Country | Canada | Austria | Australia | USA | Australia | India |
Route and frequency of administration | Enema weekly × 6 | Nasoduodenal tube (0 & 3 weeks) | Colonoscopic × 1+enema 5 day/week × 8 weeks | Colonoscopic+daily capsules | Colonoscopic × 1+ enema × 2 over 7 days | Colonoscpic every 8 weeks |
Dose of FMT | 8.3 g (50 mL)/week | 120 g | 187 g/week | 50 g+0.375 g | 100 g/week | 100 g |
Donor | Random (maximum from 1 star donor) | Random | Pooled | High butyrate | Pooled, anerobic | Single |
Placebo | Water | Autologous stool | Saline+odorant+colorant | Sham FMT+placebo capsules | Autologous stool | Water with food grade color |
Patient selection | Active UC (Mayo score ≥4) with endoscopic subscore ≥1 | Mild/moderate UC | Active UC (Mayo score 4-10) with endoscopic subscore ≥1 and physician global assessment ≤2 | Mayo score 4-10. Pretreated with 7-day antibiotics | Mayo score 3-10 with endoscopic subscore ≥2 | In remission following colonoscopic FMT |
Definition clinical remission | Mayo score ≤2 with endoscopic subscore reduction ≥1 | SCCAI ≤2 + ≥1 point decrease in Mayo endoscopic score | Steroid free with Mayo score ≤2 with endoscopic subscore reduction ≥1 and all subscores ≤1 | Mayo score <3 | Steroid free with Mayo score ≤2 with endoscopic subscore reduction ≤1 | Steroid free Mayo score ≤2 with all subscores ≤1 |
Definition clinical response | Reduction in Mayo score ≥3 | SCCAI reduction ≤1.5 | Reduction in Mayo score ≥3 | Reduction in Mayo score ≥3 | Reduction in Mayo score ≥3 | NA |
Primary end point | Week 7 | Week 12 | Week 8 | Week 12 | Week 8 +1 year follow up | Week 48 |
No. | 75 | 48 | 81 | 15 | 73 | 61 |
Study group/controls | 38/37 | 23/25 | 41/40 | 07 vs. 8 | 38/35 | 31/30 |
Remission | 24% vs. 5% (P=0.03) | 30.4% vs. 32% (P=0.1) | 27% vs. 8% (P=0.021) | 29% vs. 13% | 32% vs. 9% (P=0.03) | 87.1% vs. 66.7% (P=0.111) |
Response | 39% vs. 24% (P=0.16) | 47.8% vs. 52% (P=NA) | 54% vs. 23% (P=0.004) | 29% vs. 0% | 55% vs. 23% (P=0.007) | Endoscopic remission 58.1% vs. 26.7% (P=0.026) |
Benefit | Yes | No | Yes | Yes | Yes | Yes |
Histological improvement | Yes | Not studied | Not studied | Decreased inflammation 66% vs. 16.6%; remission 50% vs. 0% | Not studied | Histological remission 45.2% vs. 16.7% (P=0.033) |
Microbiota diversity | Improved | Improved | Improved at 4 weeks and 8 weeks | Not studied | Not studied | |
Microbiota composition | Improved | Improved | Fusobacterium associated with lack of remission | Not studied | Not studied | |
Severe adverse effects | 3% vs. 2% | Nil | 2% vs. 1% | Not mentioned | 3% vs. 2% | Nil |
Mild adverse effects | Not mentioned | 78.3% vs. 64% (P=0.28) | 78% vs. 83% | Not mentioned | Not mentioned |
Characteristics | Value (n = 27) |
---|---|
Age (yr) | 33 ± 9 (18–50) |
Male sex | 18 (66) |
Disease duration (yr) | 4 ± 4 (1–18) |
Extent of disease at inclusion | |
E1, proctitis | 2 (7) |
E2, left sided | 10 (37) |
E3, pancolitis | 15 (56) |
Medications for 3 mo before inclusion | |
Glucocorticoids | 27 (100) |
Azathioprine |
20 (74) |
Oral 5-aminosalicylates | 27 (100) |
Rectal 5-aminosalicylates | 7 (26) |
Biologicals experienced | 2 (7) |
Hemoglobin (g/L) | 12.0 (8.6–16.6) |
WBC count (× 103/mm3) | 7.2 (5.2–12.4) |
CRP (mg/L) | 5.6 (0.3–133.1) |
Peak Mayo score | 11 (9–12) |
Mayo score at inclusion | 5 (4–10) |
Parameter | Clinical remission (n = 13) | Non-responder (n = 14) | P-value |
---|---|---|---|
Age (yr) | 34.7 ± 10.8 | 34.1 ± 7.2 | 0.877 |
Male sex | 7 (53.8) | 11 (78.5) | 0.236 |
Duration of UC (yr) | 5.5 ± 1.9 | 4.7 ± 2.8 | 0.628 |
Peak Mayo score | 10.9 ± 0.9 | 11.0 ± 1.0 | 0.835 |
Mayo score at recruitment | 5 (4–9) | 10 (4–10) | 0.052 |
Donor age (yr) | 41.0 ± 10.9 | 33.0 ± 11.3 | 0.056 |
Donor sex (male) | 6 (46.0) | 10 (71.4) | 0.182 |
Spousal donor | 4 (30.8) | 5 (35.7) | 1.000 |
Extent of disease | |||
E1 disease | 0 | 2 (14.2) | 0.482 |
E2 disease | 5 (38.4) | 5 (35.7) | 1.000 |
E3 disease | 8 (61.5) | 7 (50.0) | 0.704 |
Stool temperature on arrival (°C) | 14.8 ± 1.8 | 15.0 ± 3.7 | 0.872 |
Stool temperature at FMT (°C) | 31.2 ± 1.2 | 31.1 ± 0.8 | 0.828 |
Donation to FMT interval (min) | 277 (147–350) | 255 (150–360) | 0.916 |
Slurry retention time (hr) | 18 (0–82) | 10 (2–48) | 0.279 |
Oral steroids | 13 (100) | 14 (100) | 0.678 |
Azathioprine/6-MP | 10 (76.9) | 10 (71.4) | 1.000 |
Oral 5-ASA | 13 (100) | 14 (100) | 1.000 |
Rectal 5-ASA | 3 (23.1) | 5 (35.7) | 0.678 |
Patient No. | Time to first relapse (mo) | mFMT | Antibiotic use prior to relapse | Treatment of relapse | Clinical remission achieved |
---|---|---|---|---|---|
1 | 15 | No | - | rFMT | Yes |
3 | 7 | No | - | rFMT+prednisolone 20 mg | Yes |
5 | 30 | Yes | Cefixime for urinary infection | rFMT | Yes |
6 | 34 | No | - | rFMT | Yes |
9 | 10 | No | Ceftriaxone for enteric fever | rFMT | No |
10 | 7 | No | - | rFMT | Yes |
11 | 6 | No | - | rFMT+prednisolone 20 mg | Yes |
12 | 11 | Yes | - | rFMT+prednisolone 20 mg | Yes |
13 | 19 | Yes | - | rFMT+prednisolone 20 mg | Yes |
25 | 9 | Yes | - | rFMT+prednisolone 20 mg | Yes |
Variable | Author (year) |
|||||
---|---|---|---|---|---|---|
Moayyedi et al. (2015) [10] | Rossen et al. (2015) [11] | Paramsothy et al. (2017) [12] | Crothers et al. (2018) [13] | Costello et al. (2019) [14] | Sood et al. (2019) [19] | |
Country | Canada | Austria | Australia | USA | Australia | India |
Route and frequency of administration | Enema weekly × 6 | Nasoduodenal tube (0 & 3 weeks) | Colonoscopic × 1+enema 5 day/week × 8 weeks | Colonoscopic+daily capsules | Colonoscopic × 1+ enema × 2 over 7 days | Colonoscpic every 8 weeks |
Dose of FMT | 8.3 g (50 mL)/week | 120 g | 187 g/week | 50 g+0.375 g | 100 g/week | 100 g |
Donor | Random (maximum from 1 star donor) | Random | Pooled | High butyrate | Pooled, anerobic | Single |
Placebo | Water | Autologous stool | Saline+odorant+colorant | Sham FMT+placebo capsules | Autologous stool | Water with food grade color |
Patient selection | Active UC (Mayo score ≥4) with endoscopic subscore ≥1 | Mild/moderate UC | Active UC (Mayo score 4-10) with endoscopic subscore ≥1 and physician global assessment ≤2 | Mayo score 4-10. Pretreated with 7-day antibiotics | Mayo score 3-10 with endoscopic subscore ≥2 | In remission following colonoscopic FMT |
Definition clinical remission | Mayo score ≤2 with endoscopic subscore reduction ≥1 | SCCAI ≤2 + ≥1 point decrease in Mayo endoscopic score | Steroid free with Mayo score ≤2 with endoscopic subscore reduction ≥1 and all subscores ≤1 | Mayo score <3 | Steroid free with Mayo score ≤2 with endoscopic subscore reduction ≤1 | Steroid free Mayo score ≤2 with all subscores ≤1 |
Definition clinical response | Reduction in Mayo score ≥3 | SCCAI reduction ≤1.5 | Reduction in Mayo score ≥3 | Reduction in Mayo score ≥3 | Reduction in Mayo score ≥3 | NA |
Primary end point | Week 7 | Week 12 | Week 8 | Week 12 | Week 8 +1 year follow up | Week 48 |
No. | 75 | 48 | 81 | 15 | 73 | 61 |
Study group/controls | 38/37 | 23/25 | 41/40 | 07 vs. 8 | 38/35 | 31/30 |
Remission | 24% vs. 5% (P=0.03) | 30.4% vs. 32% (P=0.1) | 27% vs. 8% (P=0.021) | 29% vs. 13% | 32% vs. 9% (P=0.03) | 87.1% vs. 66.7% (P=0.111) |
Response | 39% vs. 24% (P=0.16) | 47.8% vs. 52% (P=NA) | 54% vs. 23% (P=0.004) | 29% vs. 0% | 55% vs. 23% (P=0.007) | Endoscopic remission 58.1% vs. 26.7% (P=0.026) |
Benefit | Yes | No | Yes | Yes | Yes | Yes |
Histological improvement | Yes | Not studied | Not studied | Decreased inflammation 66% vs. 16.6%; remission 50% vs. 0% | Not studied | Histological remission 45.2% vs. 16.7% (P=0.033) |
Microbiota diversity | Improved | Improved | Improved at 4 weeks and 8 weeks | Not studied | Not studied | |
Microbiota composition | Improved | Improved | Fusobacterium associated with lack of remission | Not studied | Not studied | |
Severe adverse effects | 3% vs. 2% | Nil | 2% vs. 1% | Not mentioned | 3% vs. 2% | Nil |
Mild adverse effects | Not mentioned | 78.3% vs. 64% (P=0.28) | 78% vs. 83% | Not mentioned | Not mentioned |
Values are presented as median±standard deviation (range), number (%), or median (range). Remaining 7 patients were azathioprine intolerant. WBC, white blood cell; CRP, C-reactive protein.
Values are presented as mean±standard deviation, number (%), or median (range). UC, ulcerative colitis; FMT, fecal microbiota transplantation; 6-MP, 6-mercaptopurine; 5-ASA, 5-aminosalicylates.
FMT, fecal microbiota transplantation; rFMT, rescue FMT; mFMT, maintenance FMT.
UC, ulcerative colitis; FMT, fecal microbiota transplantation; SCCAI, Simple Clinical Colitis Activity Index; NA, not available.