Title: The Effect of Biological Agent on Body Composition in Patients with Crohn’s Disease
Version: 1 Date: 12 Dec 2022
Reviewer's report:
Low muscle mass is common in inflammatory diseases such as Crohn’s disease and is often
associated with a worse prognosis. Tumour necrosis factor has been implicated in the genesis
of cachexia, and antibodies to TNF have been shown to reverse that process. This retrospective
study examined body composition parameters derived from CT scans performed before and after
commencement of biologic therapy for moderate-to-severe Crohn’s disease in 112 patients. The
authors found that patients with “sarcopenia” (which they defined as a cross-sectional skeletal
muscle area at L3 vertebral level, divided by height squared, below a population-specific value)
were more likely to have significant body composition changes and increased serum albumin
after commencement of biologic therapy, and sarcopenia was associated with a trend towards the
need for subsequent surgery. The premise of the paper is simple, and the methodology appears
sound. The paper is clearly written and its findings add to the literature. I would like to make
the following suggestions:
• In the interests of standardised reporting of terms, it may be helpful to discuss consensus
definitions of sarcopenia – of which, the most used is the European Working Group on
Sarcopenia in Older Persons 2 (EWGSOP2) Cruz-Jentoft, A. J. et al. Sarcopenia: revised
European consensus on definition and diagnosis. Age Ageing 39, 412–31 (2018). This proposes
that sarcopenia is a syndrome characterised by low muscle mass and low muscle strength/
function. As this paper only examines muscle mass, it may be more accurate to use the term
myopenia, or at least discuss the use of variant terminology.
• The cutoff values used to define sarcopenia may be problematic. The definition of sarcopenia
used (49 cm2/m2 for men and 31 cm2/m2 for women) is from a paper that seems to have used the
equations from (Mourtzakis, M. et al. A practical and precise approach to quantification of body
composition in cancer patients using computed tomography images acquired during routine
care. Appl Physiology Nutrition Metabolism 33, 997–1006 (2008)) correlating CT and DXA
with the data from the KNHANES population study of DXA data (Kim, Y.-S. et al. Prevalence
of Sarcopenia and Sarcopenic Obesity in the Korean Population Based on the Fourth Korean
National Health and Nutritional Examination Surveys. Journals Gerontology Ser 67, 1107–1113
(2012)) to arrive at cutoff values. This conversion using Mourtzakis’ formula has been shown
to be inaccurate at identifying sarcopenia in CT scans of Crohn’s disease patients (Holt, D. Q.,
Strauss, B. J. G., Lau, K. K. & Moore, G. T. Body composition analysis using abdominal scans
from routine clinical care in patients with Crohn’s Disease. Scand J Gastroentero 51, 842–847
(2016)). CT-based studies in Korean subjects also vary from the cutoffs presented: one recent
study suggests 39.33 cm2/m2 for men and 27.77 cm2/m2 for women (Yoon JK, Lee S, Kim
KW, Lee JE, Hwang JA, Park T, Lee J. Reference Values for Skeletal Muscle Mass at the Third
Lumbar Vertebral Level Measured by Computed Tomography in a Healthy Korean Population.
Endocrinol Metab (Seoul). 2021 Jun;36(3):672-677).
• If skeletal muscle index is analysed as a continuous variable, it does not seem to correlate with
need for surgery (table 4, although SMI is not listed; SMA and BMI are not correlated with
surgery); does it correlate with body composition changes (this could be added to table 3)?
• The statement “biologic treatment reportedly may result in body weight gain, specific changes
in body composition are unknown and there have been no related studies” is not true. Many
studies have examined the effect of biologic drugs on body composition in Crohn’s disease
and other inflammatory conditions and have found similar effects to this study. A number of
systematic reviews exist in the area.
• The authors are right to highlight that the cohort examined may be atypical: the sex distribution,
the high prevalence of previous surgery (possibly due to selection bias as surgical patients may be
more likely to have a CT scan), the long median duration of disease prior to the commencement
of biologics, the high prevalence of 5-ASA drug use and relatively low use of thiopurine drugs
are at variance with other cohorts, and the long disease duration may be associated with the high
rates of sarcopenia seen.
• In the background, there is a discordant mixture of present tense and past tense.
• A reference is not provided for the statement “Resolving sarcopenia in CD patients is associated
with improved quality of life” – although this is likely to be true.
• It may be helpful to present the changes in key body composition parameters graphically;
perhaps with a before-after graph, distinguishing sarcopenic/non-sarcopenic subjects.
• The discussion may need some reworking to make it more cohesive and relevant to the findings.
At present it comprises many statements, sometimes without clear links.
• It is important to note that the large majority of patients were treated with an anti-TNF biologic
drug, and the mechanism of sarcopenia/cachexia reversal with these agents is likely different
than with other biologic drugs due to the direct effect on TNF. This effect is perhaps more
important than changes in nutrition and exercise theorised by the discussion section.
• Reduction in skeletal muscle mass and strength with corticosteroids is well-described; this
could be better addressed in the discussion.
• The conclusion may be reworked – perhaps highlighting the effects of anti-TNFs at reversing
cachexia/sarcopenia rather than ending the paper by discussing “problems caused by an increase
in fat mass” when such problems have not been identified by the study.
Title: The Effect of Biological Agent on Body Composition in Patients with Crohn’s Disease
Version: 1 Date: 12 Dec 2022
Reviewer's report:
Low muscle mass is common in inflammatory diseases such as Crohn’s disease and is often
associated with a worse prognosis. Tumour necrosis factor has been implicated in the genesis
of cachexia, and antibodies to TNF have been shown to reverse that process. This retrospective
study examined body composition parameters derived from CT scans performed before and after
commencement of biologic therapy for moderate-to-severe Crohn’s disease in 112 patients. The
authors found that patients with “sarcopenia” (which they defined as a cross-sectional skeletal
muscle area at L3 vertebral level, divided by height squared, below a population-specific value)
were more likely to have significant body composition changes and increased serum albumin
after commencement of biologic therapy, and sarcopenia was associated with a trend towards the
need for subsequent surgery. The premise of the paper is simple, and the methodology appears
sound. The paper is clearly written and its findings add to the literature. I would like to make
the following suggestions:
• In the interests of standardised reporting of terms, it may be helpful to discuss consensus
definitions of sarcopenia – of which, the most used is the European Working Group on
Sarcopenia in Older Persons 2 (EWGSOP2) Cruz-Jentoft, A. J. et al. Sarcopenia: revised
European consensus on definition and diagnosis. Age Ageing 39, 412–31 (2018). This proposes
that sarcopenia is a syndrome characterised by low muscle mass and low muscle strength/
function. As this paper only examines muscle mass, it may be more accurate to use the term
myopenia, or at least discuss the use of variant terminology.
• The cutoff values used to define sarcopenia may be problematic. The definition of sarcopenia
used (49 cm2/m2 for men and 31 cm2/m2 for women) is from a paper that seems to have used the
equations from (Mourtzakis, M. et al. A practical and precise approach to quantification of body
composition in cancer patients using computed tomography images acquired during routine
care. Appl Physiology Nutrition Metabolism 33, 997–1006 (2008)) correlating CT and DXA
with the data from the KNHANES population study of DXA data (Kim, Y.-S. et al. Prevalence
of Sarcopenia and Sarcopenic Obesity in the Korean Population Based on the Fourth Korean
National Health and Nutritional Examination Surveys. Journals Gerontology Ser 67, 1107–1113
(2012)) to arrive at cutoff values. This conversion using Mourtzakis’ formula has been shown
to be inaccurate at identifying sarcopenia in CT scans of Crohn’s disease patients (Holt, D. Q.,
Strauss, B. J. G., Lau, K. K. & Moore, G. T. Body composition analysis using abdominal scans
from routine clinical care in patients with Crohn’s Disease. Scand J Gastroentero 51, 842–847
(2016)). CT-based studies in Korean subjects also vary from the cutoffs presented: one recent
study suggests 39.33 cm2/m2 for men and 27.77 cm2/m2 for women (Yoon JK, Lee S, Kim
KW, Lee JE, Hwang JA, Park T, Lee J. Reference Values for Skeletal Muscle Mass at the Third
Lumbar Vertebral Level Measured by Computed Tomography in a Healthy Korean Population.
Endocrinol Metab (Seoul). 2021 Jun;36(3):672-677).
• If skeletal muscle index is analysed as a continuous variable, it does not seem to correlate with
need for surgery (table 4, although SMI is not listed; SMA and BMI are not correlated with
surgery); does it correlate with body composition changes (this could be added to table 3)?
• The statement “biologic treatment reportedly may result in body weight gain, specific changes
in body composition are unknown and there have been no related studies” is not true. Many
studies have examined the effect of biologic drugs on body composition in Crohn’s disease
and other inflammatory conditions and have found similar effects to this study. A number of
systematic reviews exist in the area.
• The authors are right to highlight that the cohort examined may be atypical: the sex distribution,
the high prevalence of previous surgery (possibly due to selection bias as surgical patients may be
more likely to have a CT scan), the long median duration of disease prior to the commencement
of biologics, the high prevalence of 5-ASA drug use and relatively low use of thiopurine drugs
are at variance with other cohorts, and the long disease duration may be associated with the high
rates of sarcopenia seen.
• In the background, there is a discordant mixture of present tense and past tense.
• A reference is not provided for the statement “Resolving sarcopenia in CD patients is associated
with improved quality of life” – although this is likely to be true.
• It may be helpful to present the changes in key body composition parameters graphically;
perhaps with a before-after graph, distinguishing sarcopenic/non-sarcopenic subjects.
• The discussion may need some reworking to make it more cohesive and relevant to the findings.
At present it comprises many statements, sometimes without clear links.
• It is important to note that the large majority of patients were treated with an anti-TNF biologic
drug, and the mechanism of sarcopenia/cachexia reversal with these agents is likely different
than with other biologic drugs due to the direct effect on TNF. This effect is perhaps more
important than changes in nutrition and exercise theorised by the discussion section.
• Reduction in skeletal muscle mass and strength with corticosteroids is well-described; this
could be better addressed in the discussion.
• The conclusion may be reworked – perhaps highlighting the effects of anti-TNFs at reversing
cachexia/sarcopenia rather than ending the paper by discussing “problems caused by an increase
in fat mass” when such problems have not been identified by the study.
Please review this paper.
user
Title: The Effect of Biological Agent on Body Composition in Patients with Crohn’s Disease
Version: 1 Date: 12 Dec 2022
Reviewer's report:
Low muscle mass is common in inflammatory diseases such as Crohn’s disease and is often
associated with a worse prognosis. Tumour necrosis factor has been implicated in the genesis
of cachexia, and antibodies to TNF have been shown to reverse that process. This retrospective
study examined body composition parameters derived from CT scans performed before and after
commencement of biologic therapy for moderate-to-severe Crohn’s disease in 112 patients. The
authors found that patients with “sarcopenia” (which they defined as a cross-sectional skeletal
muscle area at L3 vertebral level, divided by height squared, below a population-specific value)
were more likely to have significant body composition changes and increased serum albumin
after commencement of biologic therapy, and sarcopenia was associated with a trend towards the
need for subsequent surgery. The premise of the paper is simple, and the methodology appears
sound. The paper is clearly written and its findings add to the literature. I would like to make
the following suggestions:
• In the interests of standardised reporting of terms, it may be helpful to discuss consensus
definitions of sarcopenia – of which, the most used is the European Working Group on
Sarcopenia in Older Persons 2 (EWGSOP2) Cruz-Jentoft, A. J. et al. Sarcopenia: revised
European consensus on definition and diagnosis. Age Ageing 39, 412–31 (2018). This proposes
that sarcopenia is a syndrome characterised by low muscle mass and low muscle strength/
function. As this paper only examines muscle mass, it may be more accurate to use the term
myopenia, or at least discuss the use of variant terminology.
• The cutoff values used to define sarcopenia may be problematic. The definition of sarcopenia
used (49 cm2/m2 for men and 31 cm2/m2 for women) is from a paper that seems to have used the
equations from (Mourtzakis, M. et al. A practical and precise approach to quantification of body
composition in cancer patients using computed tomography images acquired during routine
care. Appl Physiology Nutrition Metabolism 33, 997–1006 (2008)) correlating CT and DXA
with the data from the KNHANES population study of DXA data (Kim, Y.-S. et al. Prevalence
of Sarcopenia and Sarcopenic Obesity in the Korean Population Based on the Fourth Korean
National Health and Nutritional Examination Surveys. Journals Gerontology Ser 67, 1107–1113
(2012)) to arrive at cutoff values. This conversion using Mourtzakis’ formula has been shown
to be inaccurate at identifying sarcopenia in CT scans of Crohn’s disease patients (Holt, D. Q.,
Strauss, B. J. G., Lau, K. K. & Moore, G. T. Body composition analysis using abdominal scans
from routine clinical care in patients with Crohn’s Disease. Scand J Gastroentero 51, 842–847
(2016)). CT-based studies in Korean subjects also vary from the cutoffs presented: one recent
study suggests 39.33 cm2/m2 for men and 27.77 cm2/m2 for women (Yoon JK, Lee S, Kim
KW, Lee JE, Hwang JA, Park T, Lee J. Reference Values for Skeletal Muscle Mass at the Third
Lumbar Vertebral Level Measured by Computed Tomography in a Healthy Korean Population.
Endocrinol Metab (Seoul). 2021 Jun;36(3):672-677).
• If skeletal muscle index is analysed as a continuous variable, it does not seem to correlate with
need for surgery (table 4, although SMI is not listed; SMA and BMI are not correlated with
surgery); does it correlate with body composition changes (this could be added to table 3)?
• The statement “biologic treatment reportedly may result in body weight gain, specific changes
in body composition are unknown and there have been no related studies” is not true. Many
studies have examined the effect of biologic drugs on body composition in Crohn’s disease
and other inflammatory conditions and have found similar effects to this study. A number of
systematic reviews exist in the area.
• The authors are right to highlight that the cohort examined may be atypical: the sex distribution,
the high prevalence of previous surgery (possibly due to selection bias as surgical patients may be
more likely to have a CT scan), the long median duration of disease prior to the commencement
of biologics, the high prevalence of 5-ASA drug use and relatively low use of thiopurine drugs
are at variance with other cohorts, and the long disease duration may be associated with the high
rates of sarcopenia seen.
• In the background, there is a discordant mixture of present tense and past tense.
• A reference is not provided for the statement “Resolving sarcopenia in CD patients is associated
with improved quality of life” – although this is likely to be true.
• It may be helpful to present the changes in key body composition parameters graphically;
perhaps with a before-after graph, distinguishing sarcopenic/non-sarcopenic subjects.
• The discussion may need some reworking to make it more cohesive and relevant to the findings.
At present it comprises many statements, sometimes without clear links.
• It is important to note that the large majority of patients were treated with an anti-TNF biologic
drug, and the mechanism of sarcopenia/cachexia reversal with these agents is likely different
than with other biologic drugs due to the direct effect on TNF. This effect is perhaps more
important than changes in nutrition and exercise theorised by the discussion section.
• Reduction in skeletal muscle mass and strength with corticosteroids is well-described; this
could be better addressed in the discussion.
• The conclusion may be reworked – perhaps highlighting the effects of anti-TNFs at reversing
cachexia/sarcopenia rather than ending the paper by discussing “problems caused by an increase
in fat mass” when such problems have not been identified by the study.
assistant