Review for 10.1186/s12876-021-02078-9 (2022)

Reviewer’s report
Title: 
Combined therapy with early initiation of infliximab following drainage of
perianal fistulising Crohn’s disease  a retrospective cohort study
Version: 
0 
Date: 
19 Sep 2021
Reviewer's report:
Abstract: 
fine and well written. Only minor comment is re: conlusion…
Authors state… "Combined therapy with early initiation of infliximab after
surgery could achieve promising results for PFCD patients"…
comment: 
I wonder whether the 
statement on early initiation of infliximab needs
to be tempered. Afterall the results have not demonstrated any significant
benefit, which was what the study set out to determine. 
Hence the natural
statement here, for the sake of clarity I wonder whether the authors would
consider highlighting this instead i.e. no benefit shown in this series.
Background - Page 3/4: 
Authors state "The traditional algorithm includes initial drainage with loose
seton for 2-3mths followed by infliximab infusion or definitive repair based on
the status of anorectal and intestinal inflammation" 
is this delay in medical treatment traditional? perhaps consensus statement or
guideline evidence may be helpful in adding weight to this sentence. I note
references used was a prospective study and a preliminary report. 
Authors state "With the number of clinicians chooses early combination therapy
increased[25], a direct comparison of long-term outcomes between early and
conventional combined treatment is urgently required."
comment: consider rewording this sentence to improve readership assimilation
Methods
Authors state.. "Based on a previous study in which a time interval of 6 weeks
between surgery and infliximab initiation was correlated with fistula closure, we
defined time interval shorter than 6 weeks as early combination therapy and
longer than 6 weeks as conventional combination therapy [24]."
comment/qns: did the authors attempt to review / find 'consensus' in recent
studies, on the question of timing of anti-TNF following definitive surgery? or
following abscess drainage? Just a thought that It might be helpful to the
readership to have a broader view on why "6weeks" was chosen as the
distinguishing timepoint between early and 'conventional' therapy; as opposed to
the 1 study referenced? 
Authors state: "Clinical fistula closure was defined as complete closure of the
fistula's external opening without discharge or discomfort. … A telephone
interview was conducted to inquire about the symptoms and maintenance"
comment/qns: was clinical fistula closure assessed via telephone? was this on
one occasion or on multiple occasions? was there any radiological confirmation
of healing?
Authors may consider acknowledging significant limitation (in their discussion)
of using 'external opening closure' as marker of healing / outcome measure in
fistula studies as highlighted by a recent core outcome set on the condition,
furthermore highlighting the work being done to build other outcome measures
including a PROM for Crohn's perianal fistula 
comment: Presumably the patients had their setons removed prior to assessing
closure in the patients who had drainages? At what point was this done? 
Results:
* Did the authors consider excluding those fistulas invading adjacent organs, as
this complexity may affect the healing rates? 
* Table 1 suggests Most patients had 
seton drainage procedures (96% of early vs
75%late) with very few comparative definitive treatment. I wonder if the title of
this manuscript is better suited to addressing timing of anti-TNF following
drainage of perianal sepsis in PFCD? as opposed to 'surgery' - especially in view
of the 
comparatively few definitive surgical interventions actually assessed…
Authors state "Seventy-four (63.2%) patients have achieved fistula closure at the
end of follow-up. Among them, 57 (48.7%) patients have achieved fistula
closure without any re-intervention free fistula closure)".
comment: Considering that majority had seton drainages (103/117, 88%), was
seton removal done manually or did they have another anaesthetic for removal?
and was this not considered a reintervention? just trying to help the reader easily
understand how a significant proportion of the 48.7% would have had seton
drainages and no further intervention prior to fistula closure
Discussion
Authors state: Heterogeneity in outcome definition hampers effective data
analysis and comparison between different studies about PFCD treatments. In
solutions try to address this issue, we used the need for fistula
‐
related re-
intervention as the primary endpoint. 
comment: In the abstract and methods authors state that "primary outcome was
to compare fistula closure and surgical re-intervention between early and
conventional combination groups." Probably worth deciding which one of
closure OR reintervention was the primary outcome for consistency. 
Authors state: Maintenance infliximab therapy more than 3 times is another risk
factor for surgical re-intervention in early combination group. Unlike previous
studies, which showed that maintenance therapy with infliximab could reduce
the risk of surgery and improve fistula closure in patients with PFCD [4,24].
This difference, however, may due to patients who need infliximab maintenance
therapy more than 3 times in our study usually have more refractory fistulas,
which required intermittent surgical intervention for local optimization. 
comment: I wonder if this is difficult to speculate on, particularly as the reasons
could 
be markedly different if characterising the 'surgery' according to drainage
vs. definitive surgical techniques. 
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