Reviewer's report
Title:Long-term follow-up with leukocytapheresis re-treatment in patients with
chronically active inflammatory bowel disease
Version: 1Date:23 March 2010
Reviewer: Eugeni EDM Domenech
Reviewer's report:
Observational study assessing the efficacy and safety of treatment with
granulocyte and monocyte apheresis (GMA) in patients with chronically active,
refractory, inflammatory bowel disease, including 25 patients with Crohn’s
disease and 15 with ulcerative colitis.
The strengths of the study are the homogeneous selected group of patients with
refractory disease, and data on re-treatment with GMA in case of relapse.
Major compulsory revisions:
- Introduction: given that most patients in the study were treated with steroids and
immunomodulators, and only a minority with biologicals, it seems that comments
about safety profile of biologicals should be changed by those references
showing that the greatest risk (at least for opportunistic or severe infections)
comes from combination therapies (including two out of steroids, IMS, or
biologicals) (TREAT registry; Toruner et al, Gastroenterology).
- Patients: 21 out of 25 CD patients had extensive colonic disease, and only 3/25
had small bowel involvement. This does not reflect real life. Were CD patients
treated with GMA because of their colonic involvement by analogy to UC (in
which there is a greater clinical experience with GMA)? Please comment.
- Patients: 16 out of 25 CD patients “declined” the use of biologicals. Please
provide of explanation of why 64% of patients refuse a treatment with proven
efficacy (in broth RCTs and clinical practice) and accepted be treated with a
device with such a limited experience in CD.
- Patients: Which were the criteria to decide the number of GMA sessions?
- Results: Which was the median (range) steroid dose at the time GMA was
started?
- Results: results of efficacy should be given in terms of given as the proportion
of patients achieving steroid-free clinical remission as long as this is the most
interesting clinical end-point in this sort of IBD patients. In addition, a survival
curve to show the time to achieve steroid-free clinical remission should be of
interest. A survival curve of maintenance of first remission would be of interest,
too, given that almost 60% of initially responding patients has a relapse.
- Results: were patients maintained on immunomodulators during and after GMA
success? How many of them?
- Discussion: the authors state that patients responding to a first course of GMA
usually responded to further courses if they relapse; thus, once a successful
course has occurred, GMA should be considered for the treatment of later
relapses. However, 58% of initial responders had, at least, a relapse. Taking into
account that all the patients were refractory to all accepted drugs for
maintenance therapy (5-ASA, immunomodulators and biologicals), it sounds
reasonable that GMA would have been used in a scheduled manner. Why
re-treatment and not maintenance therapy? Please comment.
- Discussion: how do the authors explain the high relapse rate if patients
- Discussion: the authors assume a supposition that 10% of their patients would
have entered in remission spontaneously. This is a “free” assumption because
this was an observational, non-randomized, non-comparative study. This
sentence should be removed.
- Discussion, last paragraph: the authors conclude that, for their immune
characteristics, GMA may be efficient in patients with chronically active IBD. As
long as immune characteristics were not assessed in these patients, this should
not be a conclusion of the study.
Minor essential revisions:
- Table 1: please provide data regarding active smokers in each group.
- Table 2: please provide statistical significance.
- Figures: what does it mean the data pooled as “after ”?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Long-term follow-up with leukocytapheresis re-treatment in patients with
chronically active inflammatory bowel disease
Version: 1Date:23 March 2010
Reviewer: Eugeni EDM Domenech
Reviewer's report:
Observational study assessing the efficacy and safety of treatment with
granulocyte and monocyte apheresis (GMA) in patients with chronically active,
refractory, inflammatory bowel disease, including 25 patients with Crohn’s
disease and 15 with ulcerative colitis.
The strengths of the study are the homogeneous selected group of patients with
refractory disease, and data on re-treatment with GMA in case of relapse.
Major compulsory revisions:
- Introduction: given that most patients in the study were treated with steroids and
immunomodulators, and only a minority with biologicals, it seems that comments
about safety profile of biologicals should be changed by those references
showing that the greatest risk (at least for opportunistic or severe infections)
comes from combination therapies (including two out of steroids, IMS, or
biologicals) (TREAT registry; Toruner et al, Gastroenterology).
- Patients: 21 out of 25 CD patients had extensive colonic disease, and only 3/25
had small bowel involvement. This does not reflect real life. Were CD patients
treated with GMA because of their colonic involvement by analogy to UC (in
which there is a greater clinical experience with GMA)? Please comment.
- Patients: 16 out of 25 CD patients “declined” the use of biologicals. Please
provide of explanation of why 64% of patients refuse a treatment with proven
efficacy (in broth RCTs and clinical practice) and accepted be treated with a
device with such a limited experience in CD.
- Patients: Which were the criteria to decide the number of GMA sessions?
- Results: Which was the median (range) steroid dose at the time GMA was
started?
- Results: results of efficacy should be given in terms of given as the proportion
of patients achieving steroid-free clinical remission as long as this is the most
interesting clinical end-point in this sort of IBD patients. In addition, a survival
curve to show the time to achieve steroid-free clinical remission should be of
interest. A survival curve of maintenance of first remission would be of interest,
too, given that almost 60% of initially responding patients has a relapse.
- Results: were patients maintained on immunomodulators during and after GMA
success? How many of them?
- Discussion: the authors state that patients responding to a first course of GMA
usually responded to further courses if they relapse; thus, once a successful
course has occurred, GMA should be considered for the treatment of later
relapses. However, 58% of initial responders had, at least, a relapse. Taking into
account that all the patients were refractory to all accepted drugs for
maintenance therapy (5-ASA, immunomodulators and biologicals), it sounds
reasonable that GMA would have been used in a scheduled manner. Why
re-treatment and not maintenance therapy? Please comment.
- Discussion: how do the authors explain the high relapse rate if patients
- Discussion: the authors assume a supposition that 10% of their patients would
have entered in remission spontaneously. This is a “free” assumption because
this was an observational, non-randomized, non-comparative study. This
sentence should be removed.
- Discussion, last paragraph: the authors conclude that, for their immune
characteristics, GMA may be efficient in patients with chronically active IBD. As
long as immune characteristics were not assessed in these patients, this should
not be a conclusion of the study.
Minor essential revisions:
- Table 1: please provide data regarding active smokers in each group.
- Table 2: please provide statistical significance.
- Figures: what does it mean the data pooled as “after ”?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Long-term follow-up with leukocytapheresis re-treatment in patients with
chronically active inflammatory bowel disease
Version: 1Date:23 March 2010
Reviewer: Eugeni EDM Domenech
Reviewer's report:
Observational study assessing the efficacy and safety of treatment with
granulocyte and monocyte apheresis (GMA) in patients with chronically active,
refractory, inflammatory bowel disease, including 25 patients with Crohn’s
disease and 15 with ulcerative colitis.
The strengths of the study are the homogeneous selected group of patients with
refractory disease, and data on re-treatment with GMA in case of relapse.
Major compulsory revisions:
- Introduction: given that most patients in the study were treated with steroids and
immunomodulators, and only a minority with biologicals, it seems that comments
about safety profile of biologicals should be changed by those references
showing that the greatest risk (at least for opportunistic or severe infections)
comes from combination therapies (including two out of steroids, IMS, or
biologicals) (TREAT registry; Toruner et al, Gastroenterology).
- Patients: 21 out of 25 CD patients had extensive colonic disease, and only 3/25
had small bowel involvement. This does not reflect real life. Were CD patients
treated with GMA because of their colonic involvement by analogy to UC (in
which there is a greater clinical experience with GMA)? Please comment.
- Patients: 16 out of 25 CD patients “declined” the use of biologicals. Please
provide of explanation of why 64% of patients refuse a treatment with proven
efficacy (in broth RCTs and clinical practice) and accepted be treated with a
device with such a limited experience in CD.
- Patients: Which were the criteria to decide the number of GMA sessions?
- Results: Which was the median (range) steroid dose at the time GMA was
started?
- Results: results of efficacy should be given in terms of given as the proportion
of patients achieving steroid-free clinical remission as long as this is the most
interesting clinical end-point in this sort of IBD patients. In addition, a survival
curve to show the time to achieve steroid-free clinical remission should be of
interest. A survival curve of maintenance of first remission would be of interest,
too, given that almost 60% of initially responding patients has a relapse.
- Results: were patients maintained on immunomodulators during and after GMA
success? How many of them?
- Discussion: the authors state that patients responding to a first course of GMA
usually responded to further courses if they relapse; thus, once a successful
course has occurred, GMA should be considered for the treatment of later
relapses. However, 58% of initial responders had, at least, a relapse. Taking into
account that all the patients were refractory to all accepted drugs for
maintenance therapy (5-ASA, immunomodulators and biologicals), it sounds
reasonable that GMA would have been used in a scheduled manner. Why
re-treatment and not maintenance therapy? Please comment.
- Discussion: how do the authors explain the high relapse rate if patients
- Discussion: the authors assume a supposition that 10% of their patients would
have entered in remission spontaneously. This is a “free” assumption because
this was an observational, non-randomized, non-comparative study. This
sentence should be removed.
- Discussion, last paragraph: the authors conclude that, for their immune
characteristics, GMA may be efficient in patients with chronically active IBD. As
long as immune characteristics were not assessed in these patients, this should
not be a conclusion of the study.
Minor essential revisions:
- Table 1: please provide data regarding active smokers in each group.
- Table 2: please provide statistical significance.
- Figures: what does it mean the data pooled as “after ”?
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
assistant