Review for 10.1186/s12876-021-01650-7 (2021)

Reviewer’s report
Title: 
High infliximab trough concentrations are associated with sustained
histologic remission in inflammatory bowel disease: a prospective cohort study
Version: 
0 
Date: 
06 Oct 2020
Reviewer's report:
Wilson et al report on a prospective study of IFX trough levels and associations
with histological healing in IBD. While the novel aspect of their work is
important there are a number of major limitations that mean this work should be
seen as a pilot rather than showing any definitive evidence. The statistics are
well done but don't reduce flaws due to the observational nature of the study
with many variations in care and assessments.
1. It is completely unclear when and for what reasons colonoscopies where
performed. This introduces strong bias as 1/3 of patients on IFX maintenance
were excluded as they did not have 2 procedures. A truly prospective study
would have had 2 defined colonoscopies as part of the study protocol and
reduced the chance of selecting a subset of patients who for clinical reasons
required 2 procedures.
2. The histopathology assessment is open to bias. A stronger approach with
blinding of pathologists, use of scores for UC (Nancy, Geboes or Robarts) and a
2nd histopathologist reviewing would have added much needed strength. There
is a risk of considerable variation. To overcome my concerns the researcher
could at least have a blinded re-assessment of a sub set of biopsies by a 2nd
pathologist and present a kappa value.
3. I' not clear how the IFX trough levels were used for analysis. Did you use the
trough level at the study inclusion or study end or did you use an average of all
trough levels from the patient?
4. The median time between the 2 colonoscopies is 3 months. This si extremely
short. In my view way too short to call this sustained remission. Given a 3 month
follow-up between procedures this part is too weak to give meaningful insight. I
would suggest a meaningful definition of sustained remission is >6 ideally ≥12
months.
5. As there was no clear protocol for clinical care individual clinicians could
have altered dosing of IFX dependent on many factors including the initial
histology results. This would introduce an amount of bias that makes sustained
results meaningless.
6. In principle the study of histological healing in UC is much easier as the
disease is less patchy and therefore easier to study. In Cd this is far more
difficult due to the patchy nature and the fact that colonoscopy does not reach
the proximal SB. This should be acknowledged.
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CPS has received unrestricted research grants from Warner Chilcott, Janssen and
AbbVie, has provided consultancy to Warner Chilcott, Dr Falk, AbbVie, Takeda,
Fresenius Kabi and Janssen, and had speaker arrangements with Warner
Chilcott, Dr Falk, AbbVie, MSD, Pfizer and Takeda.
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Is the study design appropriate to answer the research question (including the use
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