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189© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
W. H. Sobin et al. (eds.), Managing Complex Cases in Gastroenterology,
https://doi.org/10.1007/978-3-031-48949-5_27
Chapter 27
Ulcerative Colitis Refractory
toMesalamine
DanielStein andSalinaFaidhalla
A 35-year-old woman with mild ulcerative colitis is not responding to mesalamine.
The patient is a non-smoker with no family history of IBD and no other medical
problems.
How do you manage a patient with mild UC who is not responding to
mesalamine?
When there is a concern for no response/loss of response, there must be objective
evidence of disease activity since many IBD patients can have nonspecic symp-
toms due to IBS, rectal scarring, etc. Loss of response can be dened by a worsen-
ing of clinical status, and evidence of active disease based on colonoscopy or at least
inammatory markers. After conrming disease activity, we always conrm medi-
cation adherence and rule out other possible etiologies, like infection.
Other options for mild UC include maximizing mesalamine dose if not already
done, adding topical mesalamine or topical steroids (in enema, rectal foam, or sup-
pository form), to induce remission prior to escalating to a biologic. In patients with
only mild UC, we can also consider adding curcumin or sh oil.
If the above fails, then we can proceed with evaluation for other treatment options
like anti-TNFs, other biologics, or the new small molecules.
The dosage of mesalamine is maximized and mesalamine enemas are added. In
spite of this, there is no response and alternative therapy is needed. She has heard
about the anti-TNFs and wants to avoid starting those.
D. Stein (*)
Internal Medicine, Division of Gastroenterology and Hepatology, Medical College of
Wisconsin, Milwaukee, WI, USA
e-mail: dstein@mcw.edu
S. Faidhalla
Department of Medicine Division of Gastroenterology and Hepatology, Medical College of
Wisconsin, Milwaukee, WI, USA
e-mail: sfaidhalla@mcw.edu
https://t.me/medicina_free
190
Since she wants to take anti-TNFs off the table, can you discuss the choice
between ozanimod, Ustekinumab, and vedolizumab in UC?
Vedolizumab (VDZ) binds α4β7 integrin on blood monocytes, inhibiting their
ability to enter the intestinal epithelium. It is more gut selective. VDZ is an infusion
administered every 8weeks and an effective choice in UC patients who are anti-
TNF naïve.
Ustekinumab (UST) is an interleukin inhibitor, targeting IL-12 and IL-23.
Induction is an infusion followed by self-administered injections every 8weeks. It
is an effective medication in UC patients who have failed anti-TNFs, some data sug-
gest that it is more effective in inducing and maintaining remission than VDZ.
Ozanimod is a selective sphingosine-1-phosphate receptor modulator that has
been used for relapsing MS and was recently approved in patients with moderate to
severe UC.The medication is in pill form with once-daily dosing. This is a newer
medication with some limited data. However, it seems effective in patients with
mild to moderate UC who are anti-TNF naïve. Some of the known side effects of
ozanimod include infection, malignancy, macular edema, bradycardia, and ele-
vated LFTs.
For the three treatment options outlined, there is no head-to-head comparison
study, but a meta-analysis suggests that ustekinumab could be more effective than
vedolizumab in inducing and maintaining remission in UC patients [1]. Limited
data are available about ozanimod especially when comparing it to other biologics.
When it comes to choosing a treatment, we recommend discussing with the
patient in detail available treatment options, their efcacy, side effects, and route of
administration to reach a mutual decision.
In this young patient with mild UC, no previous anti-TNF exposure, and no
chronic medical problems, ozanimod would be a reasonable choice. The fact that it
is an oral med is a benet. Vedolizumab would also be a reasonable option to start
with, given its efcacy and favorable side effect prole. Ustekinumab is also a
valid option.
What is involved with starting a patient on ozanimod?
Ozanimod is a safe, effective pill that can be used in mild-moderate UC patients
who are TNF naive. During the induction and maintenance period of the ozanimod
trial, the incidence of clinical remission was signicantly higher in the ozanimod
group when compared to the placebo group [2]. Improvement in the incidence of
histologic remission also occurred with ozanimod therapy.
When deciding to start ozanimod, you need to document vaccination or immu-
nity to varicella zoster virus prior to starting the medication. In addition, you need
to obtain an EKG, and ask about any history of uveitis or DM, as these patients
might need to see an ophthalmologist.
In women of reproductive age, it’s important to remember that there are no data
about ozanimod and pregnancy, and there is possible risk of teratogenicity in animal
studies. We must discuss if there are any plans for pregnancy and if this patient is
planning to become pregnant, we recommend against using ozanimod.
Ozanimod dosing: starter pack (7days), Days 1-4 (0.23mg), Days 5-7 (0.46mg).
Day 8 patients start the maintenance dose of 0.92mg daily.
D. Stein and S. Faidhalla
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191
Some of the reported side effects of ozanimod are infections, malignancy, macu-
lar edema, bradycardia, and elevated LFTs. When it comes to bradycardia, ozani-
mod has been shown to have a lower risk of bradycardia on long-term follow than
some other drugs in this class. This may be due to the selective nature of the drug
since it targets S1P1 and S1P5 (notice that S1P 1-3 is highly expressed in the heart).
References
1. Welty M, Mesana L, Padhiar A, Naessens D, Diels J, van Sanden S, Pacou M.Efcacy of
Ustekinumab vs. advanced therapies for the treatment of moderately to severely active
ulcerative colitis: a systematic review and network meta-analysis. Curr Med Res Opin.
2020;36(4):595–606.
2. Sandborn WJ, Feagan BG, D’Haens G, Wolf DC, Jovanovic I, Hanauer SB, Ghosh S, Petersen
A, Hua SY, Lee JH, Charles L.Ozanimod as induction and maintenance therapy for ulcerative
colitis. N Engl J Med. 2021;385(14):1280–91.
27 Ulcerative Colitis Refractory toMesalamine
https://t.me/medicina_free
193© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
W. H. Sobin et al. (eds.), Managing Complex Cases in Gastroenterology,
https://doi.org/10.1007/978-3-031-48949-5_28
Chapter 28
Managing Crohn’s inaPatient withPrior
MI
PreetikaSinh
Patient is a 58-year-old male smoker with a history of myocardial infarction 2 years
earlier, who presents with bloody diarrhea. There is a strong family history of coro-
nary artery disease. Stool cultures are negative. Colonoscopy is performed and
demonstrates moderately severe colitis with ulcers involving the entire colon. The
terminal ileum is normal. It is interpreted to be an indeterminate colitis.
Is there any role for using ANCA or ASCA antibodies in the diagnosis of
indeterminate colitis?
I do not use ASCA/ANCA for diagnosis. I think we get more information from
the clinical picture alone. But there is a role for ASCA and ANCA, in those patients
who will require colectomy. The risk of pouchitis and pouch failure is much higher
in patients who are ANCA positive.
Although it was an indeterminate colitis, it was felt clinically to be favoring
Crohn’s colitis.
Is there any role for mesalamine or sulfasalazine in milder Crohn’s colitis?
I have only one or two patients on these drugs, I rarely start Crohn’s patients on
mesalamine. However, if I had a patient with mild Crohn’s colitis who was not yet
ready to start a biologic, I might start them on mesalamine. If someone is already on
mesalamine and in remission, I would not insist on making changes.
The patient starts developing increased diarrhea and bleeding and is hospital-
ized for LGI bleeding, presumably related to colitis alone. His hemoglobin drops
from 12 to 10.
P. Sinh (*)
Division of Gastroenterology and Hepatology, Medical College of Wisconsin,
Milwaukee, WI, USA
e-mail: psinh@mcw.edu
https://t.me/medicina_free
194
You have a patient with Crohn’s disease, and a history of an MI who’s in the
hospital with GI bleeding. Would you be willing to use lovenox for DVT
prophylaxis?
Yes, we face this problem frequently. I will place the patients on lovenox unless
they develop a more signicant bleed, which we dene as a drop in hemoglobin of
two grams. In the case outlined here, I would hold the lovenox because there was a
2-point hemoglobin drop. In any other situation, it's very important to stay on
lovenox, even if they have some amount of bleeding, because there is a sixfold
increased risk of venous thromboembolism in patients who have inammatory
bowel disease, and the risk is even higher in those who have an active are
So, in those other cases I will start lovenox, while keeping a close eye on the
hemoglobin. If there was a signicant Hbg drop, I would hold the lovenox but oth-
erwise emphasize very emphatically to the primary team that patients should remain
on lovenox.
Would you be willing to start an anti-TNF in this patient with a history
of an MI?
Yes. The contraindication to using an anti-TNF in heart disease is heart failure.
There’s a black box warning from the FDA saying that anti-TNFs should not be
used in patients with NYHA classication three or four heart failure.
This is based upon the ATTACH study, which looked to see if anti-TNFs could
be used to treat heart failure because TNF levels have been shown to be increased in
heart failure. However, in patients taking 10 mg/kg of the anti-TNF there was a
higher mortality in CHF, leading to this black box warning.
However, this patient has a history of MI, but no history of clinical heart failure.
Studies have not shown any increased mortality in MI so; therefore, this would not
be a contraindication. Overall, the data on anti-TNFs in other chronic inammatory
disorders show that they might be benecial to reduce cardiovascular events over
time, in those patients who don’t have advanced CHF.
You are thinking this indeterminate colitis is favoring Crohn’s disease. How
would you like to manage that?
So, for Crohn’s colitis I would go with steroid induction rst to get the disease
into remission. And then, I would probably use an anti-TNF for maintenance.
How would you feel about using ustekinumab instead of an anti-TNF in this
patient?
The patient is 58. If he was 65, or a 70-year-old, I would be more concerned
about a higher risk of infection with anti-TNFs compared to ustekinumab in this
older age range. But this patient is younger and is admitted for acute care and there
is a lot of experience using anti-TNFs as the rst line in hospitalized patients.
Have I started patients on ustekinumab in the hospital with an induction? Yes,
primarily in patients who have had a prior anti-TNF failure.
The patient is placed on an anti-TNF, has quit smoking, and does very well for
about a year. But then the patient starts developing diarrhea and bleeding. You
check stool cultures for C diff and his NAAT is positive, but his toxin is negative.
P. Sin h
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195
How would you manage this?
First, I would try to go back and check if the patient ever had a c. diff check
before, and usually we do check c. diff at the time of diagnosis. So that means that
this patient, at some point in time, was not colonized by c diff.
But, now the c diff NAAT is positive. This could either mean colonization or
active disease. But c diff in IBD behaves differently than in non-IBD patients. I
think you have to look at the clinical picture here. We have a situation where the
patient ares and now the c diff NAAT is positive. So, even though the toxin is nega-
tive, I would treat this patient as if he has active c diff.
The next question is how would we categorize his c diff? Is it fulminant, severe,
or not severe? In severe c diff, the white blood cell count is >15,000 and the creati-
nine is >1.5. Fulminant infections are associated with severe hypotension or shock
or toxic megacolon. Non-severe infections can be treated with vancomycin 125 mg,
four times a day for ten days or daxomicin 200 mg, twice a day for ten days.
Fulminant infections are treated with vancomycin 500mg qid PO and IV metroni-
dazole. Severe infections fall between the two.
The patient is clinically deteriorating and is hospitalized. Vancomycin 500mg po
QID and IV metronidazole are started. Colonoscopy is performed and he has a
moderately severe diffuse colitis, looking like ulcerative colitis.
The patient had an indeterminate colitis that was originally diagnosed as
favoring Crohn’s disease. Since then, he quit smoking and clinically worsened.
Do you ever change your categorization, your diagnosis, from Crohn’s to UC?
When I said that the colitis was indeterminate but favored Crohn’s over UC, it
was with the understanding that there were never any granulomas on biopsy, there
were never skip lesions, and there was never any extra-colonic disease. Had these
things been present, it wouldn’t be labeled as indeterminate colitis. So, it was never
denite Crohn’s disease. And now, the patient has quit smoking, and the fact that the
disease ared when he quit smoking is more consistent with an ulcerative colitis
phenotype. What is the signicance of changing the diagnosis? This largely relates
to the drugs you would use and the prognosis if you were to perform a colectomy.
So, the patient has been relapsing in spite of being on an anti-TNF.Do you
think he is a candidate for a JAK inhibitor, is this permissible in this setting?
After all, the original diagnosis was Crohn’s, where JAK inhibitors are not
approved, and he has a coexisting c. diff infection. Do we have any idea how
JAK inhibitors perform in this setting?
He is a complicated patient, and we do have to keep the whole concept of active
c diff infection in mind. I would add to the management options possibly treating
his c diff with an FMT.It is not at all unusual that when a patient with IBD develops
c diff the c diff ares up the colitis. We are frequently faced with bumping up the
treatment regimen for UC as well as trying to get the c diff under control. We have
to be cautious with our management of the UC, however. There have been patients
maintained on high doses of steroids who were not tapered off prednisone at the
right time, and their c diff infections ared and they underwent colectomies with a
poor outcome.
28 Managing Crohn’s inaPatient withPrior MI
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196
But if we are treating the c diff and doing steroid induction and the patient is not
responding, we can say that anti-TNF treatment is a failure. Then, we can switch to
a JAK inhibitor. The benet of JAK inhibitors is that they are small molecules and
their response is not dependent on the albumin. Acutely ill patients in the hospital
are more likely to have a low albumin level. There are data showing that when there
is a low albumin level those patients are less responsive to anti-TNFs. This does not
hold true for JAK inhibitors. And in treating acute (fulminant) UC, the data are bet-
ter for using a higher dose of tofacitinib, 10 mg, three times a day for induction and
as a rescue therapy, when anti-TNFs don’t work.
P. Sin h
https://t.me/medicina_free
197© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
W. H. Sobin et al. (eds.), Managing Complex Cases in Gastroenterology,
https://doi.org/10.1007/978-3-031-48949-5_29
Chapter 29
Managing Post-Op Crohn’s
AmirPatel
A 57-year-old male is admitted with a bowel obstruction. He has no past history of
IBD and has not had a prior colonoscopy. He ends up requiring surgery for the
obstruction and is found to have an ileal stricture, which is resected, and found on
pathology to be Crohn’s. The patient is a non-smoker. There is no family history of
Crohn’s.
Does small bowel obstruction in Crohn’s usually occur at the terminal ileum?
Yes, it is usually at the terminal ileum. I’ve had one or two where they were more
proximal, usually in a younger patient who had a duodenal or jejunal stricture. But
that’s exceedingly rare. About 33% of patients with Crohn’s will have just isolated
ileal disease.
He’s never had a colonoscopy. When would you perform that?
I would do it a month post-op. You really want to assess what their phenotype is.
You want to make sure they don’t have colonic involvement. For someone who has
had prior colonoscopies, we would not repeat it at 1-month post-op; instead, we
typically repeat the colonoscopy about 6 months to a year after surgery, because
that’s when we would see some type of recurrence.
One-month post-op you do a colonoscopy and nd a normal appearing colon
and distal 20cm of ileum.
Would you put this patient on any medication for Crohn’s at this time?
I would say he’s probably low risk. He is a non-smoker and he’s older. This is his
rst operation and theoretically it’s a short, stricture. I don’t know how long he’s
had his Crohn’s disease; he might have had smoldering Crohn’s disease since his
twenties and it’s just progressed to this point.
A. Patel (*)
Dept. of Medicine, Division of Gastroenterology and Hepatology, Medical College of
Wisconsin, Milwaukee, WI, USA
e-mail: ampatel@mcw.edu
https://t.me/medicina_free
198
The high-risk individuals who I think really need biologics and thiopurines to be
started postoperatively are the smokers, the patients that are younger than 30, those
with a history of stulizing disease, and those with a history of two or more surger-
ies or who have a shorter duration of disease prior to surgery.
If I have a patient who says, “I started having diarrhea about a month ago, and all
of a sudden, I have a bowel obstruction,” then I would say that person’s at very high
risk. For our patient, I’m not that concerned. Some practitioners do order genetic
testing to see if their patient has a higher risk for postoperative recurrence, checking
the NOD-2 or CARD-15 genes. Some of us will do that to see if the patient is at a
higher risk for a recurrence. But for this gentleman, I think that his risk of recur-
rence is pretty low. You could potentially get away with not starting him on therapy
right away and wait to see what the postoperative colonoscopy shows at 6 months
to a year.
A. Patel
https://t.me/medicina_free
199© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2023
W. H. Sobin et al. (eds.), Managing Complex Cases in Gastroenterology,
https://doi.org/10.1007/978-3-031-48949-5_30
Chapter 30
Managing Pseudopolyps
PoonamBeniwal-Patel
A 45-year-old male with a 12-year history of ulcerative colitis is referred to you. His
personal gastroenterologist performed a recent colonoscopy which once again
revealed dozens of pseudopolyps scattered through the colon (last colonoscopy was
3 years earlier—with similar nding). None of these polyps looked like a conven-
tional adenoma. Random biopsies were done throughout the colon and a few pseu-
dopolyps were removed. The patient is referred to you because biopsies done in the
right colon and a pseudopolyp in the transverse colon both showed dysplasia. The
referring doctor did not anticipate these biopsy results and is referring the patient
asking you how to manage this.
What is your standard approach to surveillance in patients with chronic UC?
In general, I begin dysplasia surveillance after a patient has had pan-ulcerative
colitis for 8 years or left-sided colitis for 10 years. In patients who have been in
sustained deep remission, without a history of colon dysplasia or large post-
inammatory polyps (PIP), I generally survey the colon every 3–5 years. In con-
trast, if a patient has had extensive disease or large PIPs, I bring them back in 2–3
years. Finally, those patients with concurrent primary sclerosing cholangitis are
brought back annually for dysplasia surveillance.
In patients with multiple pseudopolyps are there any tips you have to detect
which are true adenomas? Do you bring them in more often for colonoscopic
surveillance?
I use a combination of endoscopic appearance and narrow-band imaging (NBI) to
decide whether I am encountering a PIP versus an adenoma. The endoscopic appear-
ance of a brin cap along with distinct appearances such as a mucosal bridge formed
by a long polyp are more consistent with a PIP and do not need to be biopsied.
P. Beniwal-Patel (*)
Medicine, Gastroenterology/Hepatology Division, Medical College of Wisconsin,
Milwaukee, WI, USA
e-mail: pbeniwal@mcw.edu
https://t.me/medicina_free
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