Reviewer's report
Title:Treatment of Children and Adolescents with Ulcerative Colitis by
Adsorptive Depletion of Myeloid Lineage Leucocytes as Monotherapy or in
Combination with Low Dose Prednisolone After Failure of First-line Medications
Version: 2Date:31 May 2013
Reviewer: Hien Huynh
Reviewer's report:
Tanaka et al. look at the efficacy of therapeutic Granulocyte/Monocyte
Adsorption (GMA) in achieving remission in glucocorticosteroid naive children
and adolescents with a short duration (</= 12mo) of active ulcerative colitis (UC)
despite first line salicylate medications. Treatment efficacy was assessed by
determining UC clinical activity index (CAI) and disease activity index (DAI)
before and after treatment. Clinical remission was defined as CAI </= 4 and
endoscopic remission was defined as DAI <3 and absence of stools. They
recruited a total of 24 patients into the study with a mean age of 15.3y +/- 2.3y.
Seven patients responded to first line medications, so in fact, only 17 patients
were treated GMA. 12/17 responded to initial GMA and were continued on GMA
monotherapy, while 5/17 did not, and were given prednisolone (PSL) + GMA
treatment. All 17 patients achieved clinical remission (CAI </= 4) following
treatment, while 9/17 achieved complete endoscopic remission (DAI<3).
Between the three treatment groups (5-ASA, GMA monotherapy, GMA + PSL),
progression to more therapeutics was correlated with disease severity (ie.
monotherapy had lower CAI and DAI than dual therapy). GMA therapy was
deemed safe with only minor, transient side effects including needle pain, mild
headache, nausea, and lightheadedness.
Major revisions:
The use of two different UC indices makes the results more difficult and
confusing to interpret. Would it be possible to instead assess these patients
using the Pediatric Ulcerative Colitis Activity Index (PUCAI)? If not, I suggest that
you use the more common Mayo/DAI UC index, since it assesses both clinical
and endoscopic features. This may change how you interpret the success of
GMA therapy, since only 9/17 achieved remission based on DAI.
I think the remission maintenance analysis should be presented differently. Since
you recruited between 2000 and 2012 - and I suspect they were all treated at
different times - total number of patients in remission in 2013 alone does not
necessarily reflect rate of remission. Perhaps you can present your data as time
to relapse in does that achieve complete remission. You could use the
Kaplan-Meier estimator to do this and it would account for the time
post-treatment.
What are the demographics of the 17 GMA alone? While you recruited 24
patients, the efficacy of GMA was only tested in 17 of these patients.
Redo demographic table with age, gender, baseline scores, etc. for easier
comparison and interpretation.
In addition to your analysis of DAI and CAI subgroup scores, can you analyze
whether the location of UC correlates with treatment response?
Minor points
Page 10 Line 21 “[...] and this was did provoke a relapse.”
in discussion: need to mention that While the results showed pre adn post
treatment statistical significance, the sample size was small for such a long
recruitment period. Even though GMA was successful for your study population,
the adult RCT (Sands et al. 2008) demonstrates no difference between GMA and
placebo. You could suggest or possibly perform an RCT in pediatric population
with mild to moderate UC to assess any placebo effect.
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:
No to all above
Reviewer's report
Title:Treatment of Children and Adolescents with Ulcerative Colitis by
Adsorptive Depletion of Myeloid Lineage Leucocytes as Monotherapy or in
Combination with Low Dose Prednisolone After Failure of First-line Medications
Version: 2Date:31 May 2013
Reviewer: Hien Huynh
Reviewer's report:
Tanaka et al. look at the efficacy of therapeutic Granulocyte/Monocyte
Adsorption (GMA) in achieving remission in glucocorticosteroid naive children
and adolescents with a short duration (</= 12mo) of active ulcerative colitis (UC)
despite first line salicylate medications. Treatment efficacy was assessed by
determining UC clinical activity index (CAI) and disease activity index (DAI)
before and after treatment. Clinical remission was defined as CAI </= 4 and
endoscopic remission was defined as DAI <3 and absence of stools. They
recruited a total of 24 patients into the study with a mean age of 15.3y +/- 2.3y.
Seven patients responded to first line medications, so in fact, only 17 patients
were treated GMA. 12/17 responded to initial GMA and were continued on GMA
monotherapy, while 5/17 did not, and were given prednisolone (PSL) + GMA
treatment. All 17 patients achieved clinical remission (CAI </= 4) following
treatment, while 9/17 achieved complete endoscopic remission (DAI<3).
Between the three treatment groups (5-ASA, GMA monotherapy, GMA + PSL),
progression to more therapeutics was correlated with disease severity (ie.
monotherapy had lower CAI and DAI than dual therapy). GMA therapy was
deemed safe with only minor, transient side effects including needle pain, mild
headache, nausea, and lightheadedness.
Major revisions:
The use of two different UC indices makes the results more difficult and
confusing to interpret. Would it be possible to instead assess these patients
using the Pediatric Ulcerative Colitis Activity Index (PUCAI)? If not, I suggest that
you use the more common Mayo/DAI UC index, since it assesses both clinical
and endoscopic features. This may change how you interpret the success of
GMA therapy, since only 9/17 achieved remission based on DAI.
I think the remission maintenance analysis should be presented differently. Since
you recruited between 2000 and 2012 - and I suspect they were all treated at
different times - total number of patients in remission in 2013 alone does not
necessarily reflect rate of remission. Perhaps you can present your data as time
to relapse in does that achieve complete remission. You could use the
Kaplan-Meier estimator to do this and it would account for the time
post-treatment.
What are the demographics of the 17 GMA alone? While you recruited 24
patients, the efficacy of GMA was only tested in 17 of these patients.
Redo demographic table with age, gender, baseline scores, etc. for easier
comparison and interpretation.
In addition to your analysis of DAI and CAI subgroup scores, can you analyze
whether the location of UC correlates with treatment response?
Minor points
Page 10 Line 21 “[...] and this was did provoke a relapse.”
in discussion: need to mention that While the results showed pre adn post
treatment statistical significance, the sample size was small for such a long
recruitment period. Even though GMA was successful for your study population,
the adult RCT (Sands et al. 2008) demonstrates no difference between GMA and
placebo. You could suggest or possibly perform an RCT in pediatric population
with mild to moderate UC to assess any placebo effect.
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:
No to all above
Please review this paper.
user
Reviewer's report
Title:Treatment of Children and Adolescents with Ulcerative Colitis by
Adsorptive Depletion of Myeloid Lineage Leucocytes as Monotherapy or in
Combination with Low Dose Prednisolone After Failure of First-line Medications
Version: 2Date:31 May 2013
Reviewer: Hien Huynh
Reviewer's report:
Tanaka et al. look at the efficacy of therapeutic Granulocyte/Monocyte
Adsorption (GMA) in achieving remission in glucocorticosteroid naive children
and adolescents with a short duration (</= 12mo) of active ulcerative colitis (UC)
despite first line salicylate medications. Treatment efficacy was assessed by
determining UC clinical activity index (CAI) and disease activity index (DAI)
before and after treatment. Clinical remission was defined as CAI </= 4 and
endoscopic remission was defined as DAI <3 and absence of stools. They
recruited a total of 24 patients into the study with a mean age of 15.3y +/- 2.3y.
Seven patients responded to first line medications, so in fact, only 17 patients
were treated GMA. 12/17 responded to initial GMA and were continued on GMA
monotherapy, while 5/17 did not, and were given prednisolone (PSL) + GMA
treatment. All 17 patients achieved clinical remission (CAI </= 4) following
treatment, while 9/17 achieved complete endoscopic remission (DAI<3).
Between the three treatment groups (5-ASA, GMA monotherapy, GMA + PSL),
progression to more therapeutics was correlated with disease severity (ie.
monotherapy had lower CAI and DAI than dual therapy). GMA therapy was
deemed safe with only minor, transient side effects including needle pain, mild
headache, nausea, and lightheadedness.
Major revisions:
The use of two different UC indices makes the results more difficult and
confusing to interpret. Would it be possible to instead assess these patients
using the Pediatric Ulcerative Colitis Activity Index (PUCAI)? If not, I suggest that
you use the more common Mayo/DAI UC index, since it assesses both clinical
and endoscopic features. This may change how you interpret the success of
GMA therapy, since only 9/17 achieved remission based on DAI.
I think the remission maintenance analysis should be presented differently. Since
you recruited between 2000 and 2012 - and I suspect they were all treated at
different times - total number of patients in remission in 2013 alone does not
necessarily reflect rate of remission. Perhaps you can present your data as time
to relapse in does that achieve complete remission. You could use the
Kaplan-Meier estimator to do this and it would account for the time
post-treatment.
What are the demographics of the 17 GMA alone? While you recruited 24
patients, the efficacy of GMA was only tested in 17 of these patients.
Redo demographic table with age, gender, baseline scores, etc. for easier
comparison and interpretation.
In addition to your analysis of DAI and CAI subgroup scores, can you analyze
whether the location of UC correlates with treatment response?
Minor points
Page 10 Line 21 “[...] and this was did provoke a relapse.”
in discussion: need to mention that While the results showed pre adn post
treatment statistical significance, the sample size was small for such a long
recruitment period. Even though GMA was successful for your study population,
the adult RCT (Sands et al. 2008) demonstrates no difference between GMA and
placebo. You could suggest or possibly perform an RCT in pediatric population
with mild to moderate UC to assess any placebo effect.
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:
No to all above
assistant