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224
Drug-induced lupus is pretty low risk with your anti-TNFs compared to other
medications, but it can happen. This usually occurs months or years after they’ve
been exposed to the drug. If I am thinking about drug-induced lupus, I do get some
blood work before I send them to the rheumatologist, including a CBC, CMP, anti-
double- stranded DNA, anti-histone antibodies and complement levels, C3 and C4.
And if any of those antibodies are elevated, I have them see the rheumatologist to
determine whether they have to come off anti-TNF and go on some other medication.
The rheumatologist reports that it is possible these symptoms are related to the
iniximab and she would like you to stop iniximab and switch to a different class
of drug,
Which drug would you choose?
In a patient with arthralgias like this, I’d probably go with an IL-12,23 or an
IL-23 inhibitor, so that’s ustekinumab (Stelara) or risankizumab (Skyrizi). Those
are the types of therapies I’d probably go with in a patient with Crohn’s disease.
Obviously, it also depends on the phenotype of their disease. If it’s more severe and
stricturing, then obviously I prefer the IL-12,23, and IL-23 over something like anti-
integrin therapy, vedolizumab (Entyvio). If a patient has a lot of extraintestinal
manifestations, I'll also go with Stelara or Skyrizi over Entyvio. Data suggest that
Entyvio might not be the best drug for extraintestinal manifestations, including
arthralgias.
With arthralgia and other extraintestinal manifestations, particularly psoriasis,
we have found that the IL-12,23s and IL-23s have really helped. However, the one
exception is in ankylosing spondylitis. In ankylosing spondylitis, the anti-TNFs are
clearly superior and the anti-IL 12,23s and anti-IL23s have not been that effective.
Now, if it were ulcerative colitis and not Crohn’s disease you could also consider
switching to a JAK inhibitor like tofacitinib or upadacitinib. So far, these drugs are
just approved for UC not Crohn’s (upadacitinib was recently approved for Crohn’s).
But they are very effective second-line therapies.
A. Patel
https://t.me/medicina_free
225© 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_40
Chapter 40
Use ofImmune Modulators inPatients
Being Started onAnti-TNFs
DanielStein andSalinaFaidhalla
You have a patient with moderately severe ulcerative colitis who you want to start
on an anti-TNF.He is a 32-year-old man who is a social drinker, having about 2
drinks on Saturday night and Sunday during ball games. No other medical problems.
Do you think immune modulators should be used in all patients on anti-
TNFs or are you doing more anti-TNF monotherapy with close dose monitoring?
Combination therapy with IFX and AZA is superior to monotherapy. The benet
of adding an IM to adalimumab or a different anti-TNF is not well established. We
are less likely to add AZA to Humira unless we are treating a patient with Humira
who has had secondary loss of response and antibody to IFX.
On the other hand, close dose monitoring with monotherapy can be very effec-
tive in patients on anti-TNFs. We are more likely to employ this when using IFX in
a patient over 60, to decrease the risk of bone marrow suppression and lymphoma.
We know that very high drug levels of the iniximab are as protective against anti-
body formation than immunomodulators, if not more. So that's a different approach.
If you decide to use azathioprine, how would you use it in this young male,
and for how long, noting concerns that exist about hepatosplenic T-cell lym-
phoma (HSTCL)?
Men under 35 years of age receiving long-term thiopurines (>2 years) are at a
signicantly increased risk of HSTCL, although the true incidence remains low. The
risk of HSTCL in IBD patients on combination therapy is about 1:3500. This
D. Stein (*)
Department of 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
226
usually doesn’t affect our decision to start the medication. But we always discuss
the risk with the patient beforehand.
While we feel this is a small risk, one strategy to reduce the risk even further is
to use a lower dose of azathioprine. We can target lower 6TG levels, a 6TG level of
100–120 is enough to prevent antibody formation.
We can also stop the azathioprine earlier. We think that once you get two years
out that the benet with combination therapy, probably isn’t there. If you look at
when people are going to get antibodies, they usually get it, within the rst year. The
cases of HSTCL have occurred in patients taking azathioprine for >2 years.
You can also do monotherapy with anti-TNF alone with close dose monitoring.
Do you ever use methotrexate as your immune modulator in treating IBD?
How do you administer it?
In UC, there are limited data on using methotrexate in combination with anti-
TNFs. Currently, MTX is not commonly used in adult patients with UC. However,
in CD there are data supporting use of methotrexate to reduce immunogenicity and
improving drug concentrations when used in combination with an anti-TNF agent.
This may be the preferred immunomodulator for combination therapy in those at
higher risk of adverse effects of thiopurines such as young men or those with mul-
tiple skin cancers.
We do use methotrexate occasionally in our practice for select patients.
For combination therapy, we use an oral dose of 12.5mg per week. This low dose
works to prevent antibody formation. The only time we use MTX IM or SC is when
we use it as monotherapy in CD at a dose of 25mg weekly.
Alcohol use in this case would make using methotrexate risky.
D. Stein and S. Faidhalla
https://t.me/medicina_free
227© 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_41
Chapter 41
Pyoderma Gangrenosum
PoonamBeniwal-Patel
A 27-year-old female presents with acute ulcerative colitis and a skin rash on her
legs, which is diagnosed as pyoderma gangrenosum. Colonoscopy revealed a mild-
moderate severity pancolitis.
Does someone have to have severe ulcerative colitis to develop pyoderma
gangrenosum? What therapy would you use to treat the UC and the pyoderma
in this patient? Is a dermatologist always involved?
You can see pyoderma gangrenosum in someone with mild IBD.We had one
patient who had very severe PG and never had any GI symptoms. He had several
colonoscopies that looked normal and revealed only minimal histologic evidence of
ulcerative colitis.
PG severity does not have to correlate with bowel disease activity. I would say
that about half of the patients I’ve seen with PG have severe colitis and half do not.
The best treatment for PG is anti-TNF drugs. I prefer iniximab. So, even if they
have just mild UC, I would treat them with an anti-TNF if they have biopsy-
proven PG.
There is a dermatologist involved in the beginning to do a skin biopsy and make
the diagnosis. But after that, they generally leave the management up to us, since
treating the patient with anti-TNFs usually heals the skin lesions as well as the
IBD.Occasionally, the dermatologist will use topical steroids, but the mainstay is
the anti-TNF.
P. Beniwal-Patel (*)
Medicine, Gastroenterology/Hepatology Division, Medical College of Wisconsin,
Milwaukee, WI, USA
e-mail: pbeniwal@mcw.edu
https://t.me/medicina_free
229© 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_42
Chapter 42
UC inaPatient Who Failed Mesalamine
andAnti-TNF
DanielStein andSalinaFaidhalla
A 33-year-old female has moderate left-sided UC.She has tried and failed mesala-
mine and Humira (with azathioprine) and needs a change of therapy to treat her
symptoms.
How would you feel about each of these options in a patient with moderate
UC who has failed an anti-TNF? (a) Vedolizumab (b) Ustekinumab (c)
Ozanimod (d) Tofacitinib
UST is one option. It has proven effective in patients who have failed an anti-
TNF.It is an injectable medication, which is convenient in patients who have work
or school.
UST has been found to be more effective than vedo in inducing and maintaining
remission as a second-line therapy in Crohn’s disease in a network meta-analysis.
So, vedo is not our rst choice in patients who have failed an anti-TNF.
We would not recommend ozanimod in a patient who failed anti-TNF, since the
original study population had only a small percentage of patients who failed
anti-TNF.
Tofacitinib is a Jak1/JAK3 inhibitor that is approved for moderate to severe UC
patients who have failed anti-TNFs. Upadacitinib is a specic JAK1 inhibitor, which
D. Stein (*)
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical
College of Wisconsin, Milwaukee, WI, USA
Department of Medicine Division of Gastroenterology and Hepatology, Medical College of
Wisconsin, Milwaukee, WI, USA
e-mail: dstein@mcw.edu; sfaidhalla@mcw.edu
S. Faidhalla
Department of Medicine Division of Gastroenterology and Hepatology, Medical College of
Wisconsin, Milwaukee, WI, USA
https://t.me/medicina_free
230
is also effective. Our clinical experience suggests that it is possibly more effective
than tofacitinib, and there is some consensus that it has a more favorable side-effect
prole, given that it’s more selective. However, since this is a young female who
may have plans for pregnancy, we would want to avoid any JAK inhibitor and ozani-
mod at this time, and we would probably choose UST.
IFX can be considered if the patient failed adalimumab; however, most of us are
turning to the JAK inhibitors in patients who have failed anti-TNFs.
D. Stein and S. Faidhalla
https://t.me/medicina_free
231© 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_43
Chapter 43
Patients withIBD Who Are Squeamish
About Rectal Meds andSelf-Injection
AmirPatel
A 20-year-old college sophomore presents with chronic UC that previously involved
the left colon to the splenic exure. She had been doing well, taking mesalamine for
a year but over the past month started having increased bowel frequency, urgency,
and rectal bleeding. Her community gastroenterologist repeated her colonoscopy
and noted active inammation in the rectum, with the rest of the colon looking fairly
normal. The woman is going to school 1000 miles away on a fairly rural campus.
Her doctor recommends that she try rectal meds– either suppository or enema– but
she gets squeamish thinking about this and doesn’t want to try. He also discusses
possibly using Humira, but she is frightened about self-injection.
This gastroenterologist, who frequently sends you patients for a second
opinion, calls and curbsides you with these questions:
Do you have any tips for convincing a patient to try taking a rectal med? If
so, are you more successful in getting them to take suppositories, foams,
or enemas?
Do you have any tricks for dealing with patients who are reluctant to do
self-injection?
A lot of our patients with proctitis don’t want to take rectal suppositories for
several reasons: rst, they’re uncomfortable; second, there’s a stigma of putting
something in the rectum; and third, sometimes it’s really hard to retain suppositories
or enemas, if there’s signicant inammation, and they have a lot of urgency and
diarrhea already.
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
232
Injections are another problem. We have a lot of young individuals diagnosed
with IBD who don’t want to self-inject or they’re afraid of needles. This is some-
times very difcult to manage. What we typically do in the clinic is discuss with
them the risks if their disease goes uncontrolled and what the benets of our medi-
cations are. So, we have that risk and benet talk. Because the truth is that if they
don’t get their proctitis under control, there’s always a chance the disease may prog-
ress. There’s an increased risk of ares. And, obviously, there’s concern for the
increased risk for cancer.
So, we have that discussion and see if they’re willing to try the rectal supposito-
ries or the self-injections. But unfortunately, I don’t have any other tricks to con-
vince them otherwise.
In terms of choosing between suppositories, foam, and enemas, if it’s just proc-
titis involving the last 5cm of the rectum, I think that suppositories are the ideal
route. Typically, they can be easier to retain than enemas. If you’re talking about
more left-sided colitis, where there’s involvement to the splenic exure, then I
would use enemas. And here I’m talking about mesalamine. Now, we do have
hydrocortisone foams as well. And some patients feel that they can retain those better.
There is also a small subset of patients who may have a paradoxical response to
mesalamine. So, if they try Canasa suppositories or Rowasa enemas, which are both
mesalamine products, and they get a paradoxical response, you’re typically going to
switch them to hydrocortisone enemas or foams as a substitute.
Do you have any experience with tacrolimus suppositories?
Yes, tacrolimus suppositories have been around, and they’re usually dosed at
2mg twice a day. We typically reserve those for patients who are refractory to mesa-
lamine or steroid suppositories. I use them rarely. There have been several studies,
one was a head-to-head study looking at tacrolimus versus steroids, and while that
study didn’t nd tacrolimus superior in controlling symptoms, there was another
study of about 40 patients that did show a benet. So, I am using it for those who
are willing to take suppositories but haven’t had a robust response to mesalamine or
steroid suppositories. And I typically give it for about a month to see if it helps. But
obviously, a lot of times, this is just a bridge until you nd them an appropriate
maintenance therapy.
A. Patel
https://t.me/medicina_free
233© 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_44
Chapter 44
Colon Stricture inUC
PoonamBeniwal-Patel
A 58-year-old female with chronic ulcerative colitis managed with iniximab comes
to see you for a surveillance colonoscopy. Her last gastroenterologist just retired,
and her last colonoscopy was 3 years ago. Colonoscopy and random biopsies were
unremarkable, showing chronic UC in remission. Now on colonoscopy, you nd
mild inammation in the rectum, descending colon and transverse colon. But when
you get to the ascending colon, there is narrowing, and you cannot advance the
colonoscope to the cecum. There is minor inammation in the ascending colon but
no suggestion of a tumor or dysplasia. Biopsies distal to the narrowing and blind
biopsies within the narrowed segment are unrevealing; there is no dysplasia found.
Do you feel compelled to investigate this “stricture” in some other way? If
so, how?
Anytime a stricture is encountered, the diagnosis needs to be reevaluated. If there
truly is a stricture present, this suggests a diagnosis of possible Crohn’s disease
instead of ulcerative colitis. This nding would warrant a review of prior colonos-
copies and cross-sectional imaging. The next step would be a CT or MR enterography.
Can you really delineate brosis on an MR enterography?
There have been research studies showing that MRE can distinguish between
active inammation versus brotic lesions; however, this is not done as standard
clinical practice.
Assuming there is a true colon stricture in a patient with IBD, do you feel
compelled to send the patient to surgery? And, if you do, do you think it is suf-
cient for the surgeon to do a right hemicolectomy or is a more extensive resec-
tion indicated?
P. Beniwal-Patel (*)
Medicine, Gastroenterology/Hepatology Division, Medical College of Wisconsin,
Milwaukee, WI, USA
e-mail: pbeniwal@mcw.edu
https://t.me/medicina_free
234
I have encountered a number of patients with ascending colon strictures, and this
is in the setting of people feeling well. So, then the question becomes what do you
do? And in those patients, I actually have sent them to surgery, because you don’t
know what’s on the other side of the stricture. You can’t survey it for disease activity
or, more importantly, dysplasia. And so, if someone truly has an ascending colon
stricture, I would send them to surgery.
To answer the question how extensive a resection is necessary, there are cases
(e.g., limited colonic Crohn’s involvement), where a right hemicolectomy can be
considered over a total colectomy. It really is decided on a case-by-case basis and
includes consideration of several factors, such as which medications a patient has
tried, disease trajectory, and overall health status.
P. Beniwal-Patel
https://t.me/medicina_free
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