Review for 10.1186/s12876-022-02584-4 (2022)

Title: Medication Use Among Patients with Crohn’s Disease or Ulcerative Colitis Before and
After the Initiation of Advanced Therapy
Version: 3 Date: 09 Apr 2022
Reviewer's report:
The authors Theresa Hunter et al. in their manuscript try to establish the influence of modern
therapeutics on the prescription of pain medication in patients with inflammatory bowel diseases
(IBD). In order to do this, they use claims data from a large US health insurance provider. They
are able to show a drop in filled prescriptions for pain medication after the start of a modern
IBD drug.
The scientific question is interesting and important. Pain medication in IBD is not only an
indicator of insufficiently treated disease, yet on top seems to have a negative impact on health
outcomes in itself in patients with IBD. Therefore, reduction of the need for pain medication
should be an important treatment goal in IBD. The question is also quite original. Not much is
known about the effectiveness of modern IBD drugs to reduce the amount of pain medication
used by IBD patients.
The paper is technically sound even though there are some flaws in the set-up of their
investigation. The conclusions drawn are fully supported by the data. The manuscript is mostly
well written.
Major points of critique
A) Glucocorticoids are neither analgesics nor a typical adjuvant treatment in pain as for instance
amitriptyline. In addition, glucocorticoids are not given for the relief of pain but rather to treat
inflammation. While it might be nice to show, that the use of glucocorticoids drops after the start
of steroid-sparing agents, this is outside the topic of their scientific question and has been shown
by plenty of other groups. The authors need to re-analyze their data without glucocorticoids.
B) The choice of the drugs that are summarized under the term “biologics” seem to be off.
Tofacitinib is not a biologic. While there seems to be a need to somehow combine modern IBD
drugs under an umbrella term one needs to question why the authors chose those particular drugs.
What is the difference between thiopurines, methotrexate and JAK inhibitors in the context
of IBD other than the price? The authors also fail to define the term “immunomodulatory”.
They seem to be referring to immunosuppressants that are neither glucocorticoids nor biologics
or JAK inhibitors, alas thiopurines and methotrexate. The authors need to include thiopurines,
methotrexat in their analysis or explain plausibly why they left them out. Also they need to find
a different summarizing term for the drugs included in their analysis, Personally, I do not find
the term „immunomodulatory“ appropriate to summarize thiopurines or methotrexate. These are
immunosuppressants just like infliximab, ustekinumab or tofacitinib.
Minor points of critique:
a)The authors explain their statistical methods in the abstract, which have seen rarely but then
leave out the analysis of the confounders.
b)Out of all the analgesics, opioids are the ones that seem to have the most side effects. The
authors did not mention the statistically significant reduction opoid use in Crohn’s disease.
c) Page 12, 4th paragraph: The authors should consider, if the difference between their findings
and the cited sources might be, that the authors only look at patients with newly diagnosed IBD.
Td)he authors might want to consider having one of their native English speakers read through
the manuscript once more. It looks as during one of the revisions some sentences became a little
convoluted. Two examples:
• Page 4, 2nd paragraph: I do not understand the sentence “Apart from the primary
manifestation…”
• Page 12, 2nd paragraph: I am not quite sure I understand the first sentence and I definitely do
not understand the second sentence.
e) Page 11, 2nd paragraph, 3rd sentence: “The number *of* pain medication…”