148. Improving Patient-Centric Care with Novel Therapies in Ulcerative Colitis

In this episode of NP Pulse, nurse practitioners Jessica Crimaldi and Christina Hanson explore the evolving landscape of ulcerative colitis (UC), a chronic inflammatory bowel disease affecting over a million Americans. With decades of GI experience, Jessica and Christina break down the burden of UC on patients' physical and psychosocial well-being, review distinguishing features from Crohn's disease, and examine the increasing prevalence tied to lifestyle and environmental factors. This important conversation dives into the era of precision medicine, highlighting a new generation of targeted therapies, updated clinical guidelines, and best practices for early diagnosis, management, and shared decision-making. From understanding disease severity and medication classes to addressing extraintestinal manifestations, cancer screening, and vaccination recommendations, this episode is a must-listen for NPs striving to provide optimal, up-to-date care for patients with ulcerative colitis.

Episode Transcript

(00:14):
- From the American Associationof Nurse Practitioners,
this is Cammie Hauser, nursepractitioner, nurse midwife,
and AANP
education specialist.
Welcome to this
edition of NP Pulse, thevoice of the nurse practitioner,

(00:36):
AANP’s official podcast,
bringing unique nurse practitioner voices
and expertise on issuesthat matter most to NPs
and to our patients.
As always, be sure to subscribeto this podcast, share
with your colleagues,
and check back often for new conversations
with nurse practitioners
and healthcare leadersfrom across the nation.

(00:58):
In this episode of NPPulse, nurse practitioners,
Jessica Crimaldi
and Christina Hanson explorethe evolving landscape
of ulcerative colitis,
a chronic inflammatory boweldisease affecting over a
million Americans. Withdecades of GI experience,
Jessica and Christinabreak down the burden
of UC on patient's physicaland psychosocial wellbeing,

(01:22):
review distinguishingfeatures from Crohn's Disease
and examine the increasingprevalence tied to lifestyle
and environmental factors.
This important conversationdives into the era
of precision medicine,highlighting a new generation
of targeted therapies,updated clinical guidelines,
and best practices forearly diagnosis, management

(01:45):
and shared decision making.
From understanding disease severity
and medication classes
to addressing extraintestinalmanifestations,
cancer screening, andvaccination recommendations,
this episode is a mustlisten for NPs striving
to provide optimal up-to-date care
for patients with ulcerative

(02:05):
colitis.
- Hello, welcome
to the podcast on shareddecision making amid an evolution
of novel therapies forulcerative colitis or UC.
My name is Jessica Crimaldi.
I'm a nurse practitioner atCleveland Clinic working in
gastroenterology and hepatology,
and today I'm joined
by my esteemed colleague Christina Hansen,
who is also a nurse practitioner.

(02:26):
I'll let Christina tell youa little bit about herself.
- Thanks Jessica. Yes,again, Christina Hanson,
nurse practitioner andI've been working in GI
and hepatology at South Denver GI
for a little over 18 years.
We're gonna start by talkingabout the changes we've seen in
ulcerative colitis in termsof prevalence, patient burden,

(02:46):
pathophysiologic drivers,
and the dawning era of precision medicine.
We are going to start bytalking about the changes we've
seen in ulcerative colitisin terms of prevalence,
patient burden, pathophysiologic drivers,
and the dawning era of precision medicine.
But before we get startedin our focus on UC,

(03:07):
let's take a brief minuteto review a few factors
that differentiate ulcerativecolitis from Crohn's disease,
another inflammatory bowel disease.
First, when we talk about location,
ulcerative colitis is really confined
to the large intestine, the large colon,
whereas Crohn's can impact any part
of the digestive tract fromtip to tail if you will,

(03:29):
but often affects the terminal ileum
where the small boweljoins the large colon
and the perirectal area.
Upper GI Crohn's whilepossible is quite rare
and I can probably counton one hand the amount
of patients I've had with upper GI Crohn's
over the last 20 years.
And then when we look atthe inflammatory pattern,

(03:49):
ulcerative colitis typically manifests
as continuous inflammationthroughout the large intestine
and inflammation generallylimited to the mucosal lining
of the colon, whereas Crohn'scan manifest in a patchwork
pattern or skip lesions,
which is very distinct on acolonoscopy with healthy regions
of the digestive trackinterspersed with diseased regions.

(04:10):
Crohn's inflammation can affectall layers of the bowel wall
and can lead to fistulasand stricturing disease.
And then when we look at UC in terms
of epidemiologicconsiderations, we recognize
that the incidents andprevalence trends are
both increasing.
Global UC burden now exceeds5 million patients. Specific

(04:32):
to the US over one
and a quarter million Americansare currently impacted by UC
and prevalence and incidentsare rising in the general
population as well asexpanding in both younger
and older demographics.
Jessica, why do you thinkthe incidents is increasing?
- That's a great question, Christina.

(04:52):
We believe that IBDincidents is increasing due
to the western lifestyle aswell as environmental factors.
Interestingly, researchhas shown that countries
or areas that previouslyhad low incidents of IBD
who became more industrialized
or more westernized over time also start
to develop a higher incidence of IBD.

(05:14):
We think there is a strongrelationship directly tied
to our environment and way of life.
- We recognize that UC andIBD in general has an extreme
burden on patient's qualityof life given the nature
of the disease and symptoms.
UC is associated withsignificant decrements in health
related quality of life, which are driven

(05:35):
by its heterogeneous hallmarkof disease manifestations.
Some of the cardinal features of
UC precipitating the coreburden of illness include
bowel frequency and urgency
that our patients experiencethis term called tenesmus,
which we in GI call rectal retching.
A patient has thisfeeling of constant urge

(05:56):
to have a bowel movementeven if the bowel is empty.
And this is often seen inulcerative proctitis where
that inflammation is reallylimited to the rectal area
and Jessica can probably agree with this.
It's very burdensome on our patients.
They have abdominal pain, diarrhea
and rectal bleeding, even incontinence
and fatigue, which is often a consequent
of GI blood loss or anemia.

(06:17):
And if you take all these together,
obviously dramatically impactsour patient's quality of life
and really theiractivities of daily living.
Now how about thepsychosocial gravity of UC?
We certainly see issues
with patients having increasesin anxiety, depression,
suicide, and impaired social functioning.

(06:38):
Jessica, which elementsof UC are most detrimental
to patient reported outcomes or PROs?
Have you encountered patients
with UC associated psychosocial burdens?
- Of course, Christina, inmy experience, abdominal pain
and bowel frequency
or diarrhea as you mentioned,are the most bothersome,
especially to patients whoare not able to be home

(06:58):
during the day, such asthose who might be in college
or graduate school or working.
There's a lot of anxietysurrounding the possibility
of accidents, embarrassmentabout frequent need
to use the bathroom on top ofnot feeling well in general
or having abdominal pain.
It is very common for patients with IBD

(07:19):
to have concomitant psychosocial concerns.
Most commonly we see anxiety
and depression, whichare often intertwined
with their symptoms
and stress during times ofincreased disease activity.
These symptoms can flare as well,
making them more depressed, more anxious.
Sometimes they become morereclusive as well, not wanting
to leave their house orbe in social situations.

(07:42):
It's important in thispopulation to screen
for psychosocial concerns
and there are a few tools to do that
and refer when you feel it's appropriate.
- Yeah, I think you would agree, Jessica.
This is probably the patientpopulation that we see a lot
of absenteeism from work.
They'll skip social interactions
and a lot of times are thepopulation of patients that I see

(08:03):
that are asking for some kindof work exception or FMLA just
because of the burden of their symptoms.
So how do you approachyour patients with IBD
and when discussingtheir signs and symptoms
and what they're havingto deal with on all levels
of quality of life when itcomes to their disease burden?
- I try to be as empathetic as possible.
It's very hard for some ofthese patients to even talk

(08:26):
to you about these thingsbecause of embarrassment or
because of stigma aroundsome of their symptoms.
So trying to be empathetic
and just letting themknow, you know, this is
what I do all day, these talksare perfectly normal to me.
I know they're uncomfortablefor you but we're here to help.
And then also kind ofweaving in education on
how the treatment options

(08:47):
or recommendations we give themwill hopefully improve their
symptoms as well
as decreasing their inflammationwhich meets the overall
goal of, you know, stopping togo to the bathroom less often
and less abdominal pain
and hopefully improvingtheir quality of life.
- Yeah, I think it's reallyimportant, as you said, just
to make it a comfortablespace to talk about.
You and I are are used totalking about this all day long

(09:08):
and I try to, you know,emphasize that to my patient,
you know, don't hold back the,
the more detail the better in whatever way
that it feels comfortablefor them to explain it.
It's gonna help me be ableto take care of you the best.
So I, I definitely want thesepatients to feel comfortable
with talking aboutthese types of symptoms.
Another important factorinvolved in the complexity of UC,

(09:29):
and again IBD in general is that
of extraintestinalmanifestations or EIMs.
So extraintestinal manifestationprevalence can be anywhere
from 25 to 40% across all cases of IBD
and then specific toulcerative colitis, 27%
of patients have extraintestinalmanifestations involving

(09:49):
multiple organ systems.
So it's important for us
to be asking our patientsnot only about the colonic,
the digestive symptoms, the GI symptoms,
but also any other types ofextraintestinal manifestation.
So we can see upwards of30% of involvement in joints
and this is probably one ofthe most common that I tend
to see is patients describing, you know,

(10:10):
almost like arthritic type of joint pain,
dermatologic skin rashes
and lesions up to 20%, bone involvement, 30
to 60%, uveitis or or eyes.
So 10%. So making sure we'retalking to our patients our,
do they have they had an updated eye exam.
Liver and kidney can bea rare organ involvement
but is possible a lot of ourpatients will have anemia and

(10:32):
and often notably relatedto that GI blood loss.
Again leading to that fatiguethese patients can experience.
We're gonna talk a little bitmore about extraintestinal
manifestations a littlelater in the podcast
and how primary care providerscan be more aware of these
and management they're in.
But despite the complexity
and burden of the disease alongwith the growing prevalence
and incidents we have in recentyears developed multiple new

(10:56):
treatments for thisdisease space allowing us
to utilize this idea of precision medicine
with novel targeted treatments.
So Jessica, can you take us
through a discussion onfoundations in precision medicine
and speak a bit more to thesenew novel targeted treatments
we currently have available?
- Absolutely. First, let'sdefine precision medicine

(11:17):
for IBD.
Precision medicine refers to the process
of classifying patients intosubgroups based on similar
clinical and molecular characteristics
with the ultimate goal oftailoring interventions
to each group that would mostaccurately treat their disease
with the least amount of side effects.
This has been done formany years in oncology

(11:38):
but is relatively new to the IBD field.
We know in IBD there aremany different inflammatory
pathways that can leadto bowel inflammation
and in an ideal world we would be able
to give each patient the medication
that most specifically worksto their inflammatory pathway
but we are not yet therein clinical practice.

(11:59):
To give a relatable example,when you're treating a patient
for a UTI, we typicallyreview the urine culture
and sensitivity data
and prescribe the antibioticthat is most likely
to work on the specific bacteriabased on the sensitivities.
This allows us toprecisely pick a medication
that has a high likelihood of working

(12:19):
and avoid trialing other medications
that are less effective unnecessarily.
There is no test like this for IBD
and we continue to have a population
that is sub-optimallytreated for several reasons,
including primary non-response.
This refers to when you give a medication
and it just never works forthat patient. Loss of response,

(12:40):
this refers to when thepatient has been taking the
medication and it's beenworking over a period of time
but then it loses its effect.
That can be for a number of reasons
or just an intolerance to the medication.
Sometimes the side effectsare too large for patients
to continue on with a specific therapy.
The novel therapies in IBD
that we will talk about todayare targeting new inflammatory

(13:03):
pathways that drive diseaseactivity and progression.
When thinking about thenew medications for IBD,
they are largely but notall in the biologic space
and include the followingtargets, tumor necrosis factor
or TNF, the JAK/STAT pathway,
interleukin 12 and interleukin 23
or IL-12, IL-23 cytokine cascade,

(13:26):
the Alpha-4/Beta-7 integrin signaling
and the sphingosine-1-phosphate receptor modulation.
With all the new medicationsit can be challenging
to keep up with the most recent data
and treatment algorithms.
We are fortunate to havetwo large GI societies,
the American College ofGastroenterology or ACG

(13:47):
and the American Gastroenterology Association
or AGA that both have guidelineson the management of UC.
Not surprisingly,
with the rapid growthin treatment options,
the guidelines quickly becomeoutdated prompting the AGA
to shift their approach toproviding up-to-date information.
Christina, can you compareand contrast the AGA

(14:07):
and a CG guidelines forUC and the recent updates?
- So both the AGA
- So both the AGA
and the ACG provideclinical practice guidelines
for inflammatory bowel disease,
but there definitely are some key
differences in their approach.
The AGA and ACG largely sharea similar goal improving IBD
outcomes through evidence-based practice,
but they may differ in theirspecific recommendations

(14:29):
for treatment and management,
particularly in the earlystages of moderate to severe UC.
The most recent AGA guidelineson ulcerative colitis was
actually just published in November
of 2024 in Gastroenterology,
and is termed as a living guideline,
which is focusing on thepharmacological management
of moderate to severe UC.

(14:51):
And actually we'll beupdated every six months
and obviously as youwere mentioning Jessica,
we really need this with allthese incredibly fantastic
new novel agents.
This living documentis meant to be reviewed
and updated regularlybased on new evidence
and emerging treatments with the goal
of providing the mostcurrent recommendations
for managing ulcerative colitis.

(15:11):
This updated guidelinerecommends earlier use
of more effective drugsincluding biologics
and small molecule therapiesinstead of a step up approach
with five amino salicylates,which we've historically done.
Additionally, there's anew guideline on monitoring
ulcerative colitis withnon-invasive biomarkers
and this was actuallypublished in February of 2023.

(15:32):
So we do have some updated guidelines
and recommendations from whatwe've had thus far, especially
because of, as Jessicamentioned, this wave
of new therapies that have been improved.
Colorectal cancer screening,
both societies actuallyrecommend colonoscopies
for those IBD patientswith longstanding disease
and involvement of alarge portion of the colon

(15:54):
and both utilize evidence-based approaches
to develop their guidelinesdrawing on clinical trials
and expert opinions.
While both organizationsprovide valuable guidance
for IBD management,
the AGA's guidelinesare more comprehensive
and may lean towards amore proactive early use
of advanced therapies inselected IBD cases, particularly

(16:16):
for moderate to severe UC
as I mentioned earlier.
While the ACG guidelines areactually more focused on the
specific aspects of UC careincluding hospitalized patients
and colorectal cancerprevention. Jessica, the arrival
of these disease modifying therapeutics
or DMTs places heightenedawareness on the need
for timely diagnosis

(16:36):
and linkage to treatmentwithin the disease's natural
history or what we callthis window of opportunity.
What is this term window of opportunity?
The window of opportunity in IBD
refers to the time early in the diseasecourse when medications may
be the most effective in treatingand reducing inflammation.
We know that IBD is a lifelongand progressive disease

(16:59):
and there is often a delay in diagnoses.
Greater than 50% of patients have symptoms
for at least a year beforeobtaining a formal diagnosis.
While 25% have symptoms forgreater than five years,
diagnostic delays lead to treatment delays
and to detrimental outcomes.While treatment is delayed,
patients have ongoing inflammation

(17:20):
or what some people refer toas smoldering inflammation
that over time can leadto fibrosis, strictures,
penetrating disease and even malignancy.
Treating as early as possible helps
to quiet the inflammation
before it can progress tomore serious complications.
Christina, what do you thinkare some of the main drivers

(17:41):
of the ulcerative colitis diagnostic delay
and how can patient facingclinicians help combat these
hurdles to achieve timelydiagnosis and treatment linkage?
- Well yeah Jessica, I thinkthere are certainly many
factors leading to delay of diagnosis,
including sometimesthe non-specific nature
of symptoms which can bemistaken for other diseases

(18:02):
or conditions such as irritablebowel syndrome, hemorrhoids
for rectal bleeding or simplya lack of knowledge around UC
and its associatedsymptoms which again can
lead to further delay.
Patients can often learnto live with their own norm
and I talk to my patientswith IBD about this,
you know they've beenliving with these symptoms
for a long time, maybe there'snot prolific rectal bleeding

(18:22):
that prompts them to seekmore emergent medical care
and they just kind ofthink it's their norm
and so they don't pursuemedical care for a long period
of time or sometimes they canhave a lot of embarrassment
as you mentioned earlier, over the type
of symptoms they're experiencing.
Again, leading to delay
or sometimes they simplyfear their symptoms
and potential diagnosis.
We can also find limitationsin access to care

(18:45):
with long wait times to getinto see a GI specialist
and in addition, lack of specific
and reliable diagnostic tools for UC.
Obviously if they're notundergoing a colonoscopy
immediately, which can make it difficult
to differentiate fromother conditions leading
to diagnostic delays.
In addition, approximately25 to 40% of individuals
with IBD display extraintestinal manifestations

(19:07):
as I mentioned earlier, and therange of presenting symptoms
with these EIMs can make itchallenging for clinicians
to promptly identify patients with IBD.
Symptoms can be attributed toother conditions such as IBS
as I mentioned, all again,which can lead to these delays
and some data suggests a range of delay up
to eight years or longer.

(19:28):
Now how do we combat these hurdles?
Well, I think having astrong baseline knowledge
around IBD including the signs
and symptoms, typical ages at presentation
and potentially geneticpredisposition so that
when you're talking toa patient presenting
with perhaps not extremely clear symptoms,
warranting referrals such as
that really excessive bloody diarrhea,

(19:49):
then the healthcare providerwill have a lower threshold
to ask further questionsaround these factors.
I think continued developmentof validated diagnostic tools
with high sensitivity andspecificity will also be helpful
for clinicians in the primarycare setting tools such as
that fecal calprotectin,
which we're now using a lot atbaseline when we have a high
suspicion for IBD and tomonitor treatment response

(20:10):
or when patients might be flaring.
And as we improve diagnosticdelay, we will then be able
to get more patients in duringthat window of opportunity
where early intervention,using more aggressive
and therapeutic agents certainly can lead
to better long-term outcomes,
potentially even modifying thedisease's natural progression
and we truly are armedwith an exceptional range

(20:31):
of novel targetedtherapies than we ever had
before in our armamentarium.
So Jessica, would you takeus through a general overview
of our current arsenal
and how these treatments are unique from
therapies in the past?
- Thanks Christina.
I think it's very fitting
that we're doing this talk in2025 when 20 years ago this
year the first biologicfor UC was FDA approved.

(20:54):
That was Infliximab, which many
of us in GI are very familiar with.
Since that time we've hadan additional 11 medications
approved and we will talk about some
of the most recent ones now.
Please note this discussionis not an all-inclusive list
of medications.
There are a whole slew ofmedications for more mild disease
and many medications thatcome in different forms such

(21:17):
as rectal suppositories, foams, pills,
and other medications thatare adjunct to treatments.
Today we're taking a focused look at some
of the more recent novel medications
but not all of the medications for UC.
So first up on our list arethe novel practice changing
class in UC, the JAK inhibitors.

(21:39):
Why do I say it's apractice changing class?
So this class was the veryfirst one to offer a pill prior
to the JAK inhibitors, wecould say stronger medications
for ulcerative colitis were inan IV or subq injection form.
So having a pill was really game changing.
There are currently twoavailable JAK inhibitors,

(21:59):
Tofacitinib and Upadacitinib. JAKs are enzymes
or proteins that travel tospecific surface receptors
on our immune cells. They help
to signal a messenger chemical called STAT
to tell the nucleus topromote inflammation.
When you take a JAK inhibitor,
you block some of that action.

(22:20):
Like I said, JAK inhibitorswere a game changer
because they were the firstoral pills, not injections
or infusions, they werecheaper to manufacture.
They work very quickly
and are less likely to causethe development of antibodies
or an immune reaction. Ifyou're familiar with Remicade
or Infliximab forexample, this medication
over time patients can develop antibodies

(22:42):
where it no longer works for them
or they can also have an allergic reaction
or an immune reaction.
When that happens, thatmedication is no longer available
to them as a treatment option.
So having a medication that is less likely
to cause antibodies
or an immune reaction is also a huge plus side.
Side effects
of JAK inhibitors do includean increased risk of shingles,

(23:06):
elevated cholesterol andblood clots such as PE and DVT
and cardiac events such as MIs and cancer.
Just to overview the two, again,
Tofacitinib was first FDAapproved for UC in 2018,
so we're about seven years.
It was evaluated in theOCTAVE clinical trial program.
There was OCTAVE 1

(23:27):
and OCTAVE 2 which looked at induction
and OCTAVE Sustain which looked at remission.
In the induction studiesparticipants receiving Tofacitinib
experienced a 16 to 18%level of induction compared
to placebo at 6 to 8%.In the SUSTAIN trial,
which looked at long-termremission participants receiving

(23:49):
Tofacitinib had remissionrates as high as 34
to 40% compared to just11% in the control group.
Those are pretty big numbers in IBD data.
The second drug Upadacitinib is the second JAK
and that was FDA approved forulcerative colitis in 2022
after being found to bemore efficacious than

(24:09):
placebo during induction.
The next new class ofdrugs is the Anti-IL-12/IL-23
monoclonal antibodies.
IL stands for interleukin and IL-12
and 23 are pro-inflammatory cytokines
that play a role in inducing
and maintaining intestinal inflammation

(24:30):
by actively recruiting whiteblood cells to the bowel.
There is one medicationapproved for UC in this class,
Ustekinumab. Ustekinumabwas approved in 2019.
The first dose is given as an IV infusion
so this would require the patient to go
to an infusion center
or in some areas you may beable to get an at-home infusion

(24:52):
and then that's followed
by periodic subcutaneous injections.
This can make this a moreconvenient option than strictly IV
infusions for patients,
but we do have to think aboutif our patients are willing
to self-inject or if theyhave someone who is willing
to inject them.
Adverse events with thismedication were mild
and did not appear to differ from those

(25:13):
within the placebo group.
So to review Ustekinumabblocks both the IL -2
and IL-23 signaling pathwaysto reduce inflammation.
It was evaluated andthen the UNIFI trial
and FDA approved forulcerative colitis in 2019.
In addition to the combined anti IL-12

(25:35):
and anti IL-23 combinationdrug Ustekinumab,
there are medicationsthat target IL-23 alone
and those include Mirikizumab, Risankizumab,
and Guselkumab.
If you can say all thosewithout getting tongue tied,
you're better off than I am.
They were all evaluatedin various clinical trials

(25:56):
and Mirikizumab was approvedin 2023 Risankizumab in
2024 and Guselkumab in 2024.
Guselkumab had a recent release
of positive data fromphase three ASTRO study
that laid the groundworkfor the potential approval
of a subcutaneousinjection regimen as well.
That would make Guselkumab theonly anti IL-23 monoclonal

(26:20):
antibody that is availablefor subq injection.
Lastly, on the IL-23pathway we have one drug
that has recently completeda phase two B study
and that is Icotrockinra. Johnson
and Johnson announcedjust about a month ago on
March 10th, 2025 positive topline results from ANTHEM-UC,

(26:40):
a phase two B study of Icotrockinra,
the first investigationaltargeted oral peptide
that selectively blocks theIL-23 receptors in adults
with moderately to severeulcerative colitis.
Though this is a pill form ofthe anti IL-23 pathway drugs,
this would also be a first in this class.

(27:02):
The study met its primary endpoint
of clinical response inall Icotrockinra dose groups
evaluated and demonstratedclinically meaningful differences
versus placebo in key secondaryendpoints of remission,
symptomatic remission andendoscopic improvement,
Week 12. It was welltolerated with proportions
of participants reporting one

(27:22):
or more adverse events being similar
between the placebo andthe treatment group.
The date for it
to be FDA approved is notcurrently available yet
as the data from this studyis currently being prepared
for upcoming medical congresses.
Moving on to our fourthclass, we have the Alpha-4/
Beta-7 integrin inhibitors which work

(27:45):
by blocking white blood cellsfrom attaching to tissue
and prevent them from enteringthe lining of the GI tract
and causing inflammation.
We have one medication inthis class Vedolizumab,
which was FDA approvedinitially back in 2014
for the IV route
and more recently in 2023
for the subcutaneous route which is great
for our patients givingthem another option.

(28:07):
Vedolizumab is considered tobe a gut directed medication
and does not cause systemicimmune suppression which leads
to increased safety and tolerability.
I can tell you frompersonal experience a lot
of patients want to take this medication
or may have read about itbefore their appointment or
before meeting with you
because they do advertiseit as being more specific

(28:29):
and patients really like that
it doesn't cause systemicimmune suppression like some
of the other medications.We do have newer ones
that are adding that benefit as well.
But with this havingbeen approved in 2014,
it was the only one around for a while.
And lastly we have the S1P receptor modulators,
which stands for sphingosine-1-phosphate receptor modulations

(28:52):
and agonists, which include Ozanimod,
which was approved in 2021and Estrasimod approved in 2023.
Both medications are availableas an oral pill or tablet.
S1P receptor modulators bind
to receptors found on thesurface of immune cells.
By binding they prevent theimmune cells from being released
into the bloodstreamwhich reduces the amount

(29:13):
of inflammation in patientswho have ulcerative colitis.
Side effects include a decreasedwhite blood cell count,
so a baseline level
and ongoing monitoring are needed as well
as elevated liver biochemistries.
So this would be yourAST, ALT, TBILI alk phos
potentially, decreasedheart rate, infections,
increased blood pressure, eyeproblem, and herpes infection.

(29:36):
Patients should discuss allside effects with their provider
as there may be additional ones as well
and some that concern somepatients more than others.
Just to recap, ozanimod wasevaluated in the TRUE NORTH
trial and was FDA approvedfor ulcerative colitis in 2021
and Etrasimod was evaluated in the Elevate UC 52
and 12 trial and FDAapproved for UC in 2023.

(30:01):
Now that we have discussedthe plethora of medications
that are recently arriving onthe ulcerative colitis scene,
I'm going to transition back to Christina
for a discussion onshared decision making.
- Thanks Jessica. Yeah,
I don't know if I could saythose medications three
times fast either.
So a fantastic job.
Clearly the primary care providerreally we talk about this

(30:24):
with our patients, you knowthat's your quarterback of care.
So clearly being theprimary care provider,
they'll frequently haveinteractions with patients dealing
with IBD and sometimesthis can be overwhelming
or uncomfortable for thehealthcare provider if
they're not as familiar.
Other times it's not clearwho has responsibility for
what when it comes to health maintenance
for these patients such as vaccination

(30:46):
and various screening.
We talked a bit earlier on thedifferences between Crohn's
and ulcerative colitis
and I think it's also importantto recognize the difference
between mild UC
and moderate to severe.Milder ulcerative colitis is
typically characterizedby fewer bowel movements,
maybe less than four perday, occasional bloody stools
and mild abdominal pain.
Moderate to severe ulcerativecolitis on the other hand

(31:08):
involves more frequent bowel movements,
more than four per day or evenmore than six frequent bloody
diarrhea and potentiallymore severe abdominal pain,
fatigue, weight loss or fever.
So I think the importance fora primary care provider in
following a patient with UC is
to understand symptoms canvary significantly from person
to person and even withinthe same person over time.

(31:29):
So it's crucial to have yourpatient monitor symptoms
and report any changes
and in the end you have yourGI partner to consult with
for any questions that arise.
And speaking of partnerships,
a multidisciplinary team reallyis crucial in managing those
extraintestinal manifestationsI talked about earlier,
those EIMs that we see withinflammatory bowel disease

(31:50):
because these complicationsas we reviewed earlier,
can really affect various organsystems requiring expertise
from multiple specialists.
I like to make the statementthat skin is the seventh wonder
of the world to a GI specialist.
So I'm gonna have thatpatient see the dermatologist
for assistance and figureout what's going on when
that patient presents to me with some kind
of new carbuncles on their skin, right?

(32:11):
Use of a multidisciplinaryteam approach ensures
comprehensive care encompassingthe diagnosis, treatment
and management of theseEIMs which can improve the
patient's quality of life.
And then when we think abouttargeted treatment goals over
the past 20 years, whenwe look back 20 years ago
and we think about therings on a bullseye,

(32:31):
a target if you will, wayback in the day 20 years ago,
we really initially wanted tohave our patients feel better
and then moving into thoserings a little bit closer to
that bullseye, we wanted toreduce the use of steroids
with the targeted steroid free treatment.
And then as those rings gotcloser to that bullseye,
we wanted to have endoscopic remission.

(32:52):
So when we went into scopethat patient, we wanted to see
that the mucosa looked improved.
So what was happening on theoutside, we wanted to match
what was going on on the inside.
We recognize that key efficacyendpoints though in present
day involve three categories,clinical remission,
endoscopic remission, and deep mucosal

(33:13):
or histologic remission.
So again, we want ourpatients to feel better,
we want their mucosa tolook normal endoscopically,
and then when we take biopsiesunder the microscope, we want
that deep mucosal histologic remission.
So we really want that colitisto be quiescent or inactive.
And as discussed earlier on,

(33:34):
getting patients identified earlier
and started on efficacioustreatments sooner to maximize
that window of opportunityto treat in early stages
of inflammation really reducelong-term complications
with the potential to modifythe disease in and of itself.
I think another important factor
that primary care providersneed to be mindful

(33:54):
of being often the firsttouch with the patient
for various symptoms would bepotential side effects related
to biologics or these new novel therapies.
And Jessica already took usthrough quite a few of these,
but kind of in review,when we look at the IL-12
and IL-23, so Ustekinumab
or the other IL-23 monoclonalantibody therapies, some

(34:15):
of the things that we wanna bemindful of are the potential
for upper respiratory infections,nasopharyngitis, headache,
there can be some riskof serious infection,
non-melanoma skin cancer andas well as other cancers,
although much more rarerisk. JAK inhibitors
or small molecule therapiescan have an increased risk
of infection, particularly shingles

(34:38):
or other herpes zosterinfections like Jessica mentioned
earlier, as well as thosecardiovascular considerations.
When we think about the S1Preceptor modulator,
small molecule therapies,these could be associated
with a risk of infectionsuch as UTI, again,
upper respiratory infections
or could be associated
with cardiovascular risksincluding bradycardia

(34:59):
or events like blood clotsor heart related issues.
The integrin inhibitors such
as Vedolizumab have amuch better safety profile
as Jessica mentioned, than past biologics,
but could be associated withupper respiratory infection
such as again,nasopharyngitis and headaches
and actually some GI symptomssuch as abdominal pain,
nausea or diarrhea.
Occasionally we can see anexacerbation of a patient's UC

(35:22):
or Crohn's, last risk with infection
and rare risk of progressivemultifocal leukoencephalopathy.
PML, this is a braininfection.
We don't see this asmuch with Vedolizumab as
with Natalizumab, butagain, extremely rare.
And again, these are thingsjust keep in mind obviously your
GI specialist is gonnabe initiating the therapy

(35:43):
for the patients with IBDmonitoring them as well.
But just something to bethinking about in the back
of your mind when you'rehaving patients present
with some other type of symptom.
And also with any agents
that are infused there can bea risk of infusion reactions,
but again this is somethingthat would generally be seen
fairly soon during the infusion
and managed by that infusion team.
And we would talk about key considerations

(36:04):
for patients on biologics.
Let's talk about some bestpractices around cancer screening
and vaccinations forthe PCP to be aware of.
So patients receiving any immunemodifying agents should be
counseled against receiving live vaccines.
Inactivated vaccines aresafe in patients with IBD
and their administration's not associated
with an exacerbation of IBD activity.

(36:26):
It suggested that patientsreceive vaccines at the earliest
opportunity and preferablyto be off steroids
or at the lowest tolerablecorticosteroid dose if possible.
All adult patients withIBD should be evaluated
for latent hepatitis B infection
and patients who have previouslycompleted a full hepatitis
B vaccine series
but are not seroprotectedreceive a single challenge dose

(36:49):
of hepatitis B vaccine.
In our adult patients with IBD,
we should give them an annualinactivated influenza vaccine.
We wanna avoid using liveattenuated intranasal vaccines
for this. And in allpatients with IBD ages 19
to 64 years of age,
they should receive aninitial pneumococcal vaccine

(37:10):
with subsequent secondpneumococcal vaccine administered
for those 65 years of age or older.
And all patients with IBDwho are 60 years of age
or older should receive an RSV vaccine.
There's no preference for any
of the available vaccinesin this category.
Then adult patients 19 years of age
and older receivingimmune modifying therapies

(37:32):
or if plans to initiate immunemodifying therapy should
receive a recombinantherpes zoster vaccine series
regardless of their priorvaricella vaccine status.
So in thinking of someother considerations.
Bone density screening shouldbe considered in patients
with IBD actually regardless of age
and when risk factors for osteopenia

(37:54):
or osteoporosis arepresent. All adult patients
with IBD should be screened for depression
and anxiety yearly.
And patients who screenpositive for depression
or anxiety should be referredto the appropriate specialist.
But if their primary care provider
or mental health specialist can manage it,
certainly we wanna be mindful of that
and initiate treatment as indicated.

(38:14):
And all patients
with IBD should receive ageappropriate cancer screening,
cervical dysplasia screening, colonoscopy,
prostate screening,
and in our adult patients with IBD,
we wanna make sure these patientsare having follow-up skin
cancer primary prevention,
make sure they're avoidingexcessive sun exposure.
Patients on immunomodulators,anti-tumor necrosis factor

(38:35):
or other biologic agents
or the small moleculesshould undergo yearly total
body skin exams.
And patients with any history
of thiopurine use should continue
with yearly total body skin exams,
even if they're no longer onthe thiopurine medication.
And so one of the thingsjust to think about,
anybody should be gettingyearly skin checks, right?
IBD or not. So thinking aboutmaking sure these patients are

(38:58):
getting yearly skin checkswith their dermatologist
and following those skin cancer primary
prevention practices.
And I'll reference thisa little bit later on,
but the AGA came out
with a really recent guidelineon clinical practice updates
for non colorectal cancer screening
and vaccinations in patients
with inflammatory bowel disease.
And this was an expert review
that was published inClinical Gastroenterology

(39:19):
and Hepatology here justwithin the last month.
So that's something to reference
and I'll come back to thata little bit later on.
Jessica, can you talka bit more about some
of the other key considerations
for individualizing treatmentdecisions in UC?
- Absolutely. Thank you Christina.
First and foremost, we needto have a good understanding
of the location and severityof the patient's disease

(39:42):
as this will determine whattherapies are available
for individual patients.
The majority of the medicationswe discussed earlier today
are for patients withmoderate or severe UC.
In contrast to them,
some patients really do have mild disease,
specifically patients
who have mild proctitis mayonly need suppositories or foams

(40:03):
or oral medicationsthat do not have as much
of an immune effect as some ofthe medications we discussed.
So our starting point should really be
where is their disease located
and how bad is it?
For UC specifically wethink about the risk
of colectomy being low or high
and disease severity asmild, moderate, or severe.

(40:24):
Once this has been determined,you will have a menu
of options so to speak,
but the decision on which therapy
to choose is very complicatedand cannot be done in a silo.
Multidisciplinary teams incollaboration are essential
for almost all IBD patients. Outside
of disease severity and location,
things to consider includeany impending surgeries.

(40:45):
Sometimes medications need to be held
around the perioperativetime, even if it's not related
to the bowels just
because of their immunesuppressive effects.
Any other comorbidities,things that come to mind
to me are cancers
are very high on the listas well as heart failure.
Some of our medications cannotbe given in certain classes

(41:05):
of heart failure and any other conditions
that would make somebodymore immune suppressed
or more susceptible to an infection.
Pregnancy status is also huge,
so they may not be pregnant now if you
have a female patient.
But knowing their desire andability to become pregnant
or father a child is veryimportant, especially for people

(41:27):
that are younger
and maybe you know, arenewly in a relationship
and are at that age wherethey may be thinking
about having children.
But even for those whomay be a little bit older
but are still capableof becoming pregnant,
these are things wewanna think about. As some
of these medications arenot approved for pregnancy
and some are, but may needto be stopped, you know,

(41:47):
towards the end of their pregnancy.
So a lot to consider there.
Patient's ability
and willingness to undergoserial infusions or injections.
So you know, needlephobia is a huge thing.
Access to an infusion centeror ability to get home
infusions, ability to give yourself a shot
or you know, your willingness

(42:08):
to let somebody else give you a shot.
These are all things totake into consideration.
Generally speaking,medications that are, you know,
once a day and pillsare much easier to do.
However, that's not an option for all
of them. If they're onlyable to take something
that's an IV infusion or injection,
we have to have reallyopen honest conversations

(42:28):
with patients about what they'rewilling and able to do and,
and what is practical ornot practical for them.
Even things to consider likewhat area of the country
or world they live in.
So where I'm at in Cleveland, we are not
so far from the Ohio River Valley,
which can put you at an increased risk
for fungal infections, whichis a problem for patients

(42:49):
that are on immune suppression.
So there's a lot to think about.
And lastly, the big oneI would say is insurance
with the caveat that that's unfortunate,
but sometimes insurancedoes dictate to some extent
what we are able to do.
It's imperative that we includeour patients in the decision
making process so that wepick the best medication for
that specific patient.

(43:10):
Specifically in IBD, like I said,
many medications are offered via infusion
or subQ injection,
which have much differentlogistical requirements
than a daily pill.
And it may or may notwork for all patients.
The nurse practitioneris uniquely positioned
to be often one of the veryfirst points of contact
and potentially mostfrequent points of contact

(43:31):
for an IBD patient
in a GI practice. GI physicians tend
to spend a decent portion
of their schedule in the endoscopy suite.
So the nurse practitioner
and support staff are oftenthe one that are fielding a lot
of symptom calls, managingurgent visits, making a lot
of treatment decisions.
So we have a central role inthe care of the IBD patients

(43:52):
that doesn't only includeyour clinical assessment
and diagnosis, but also recognition
of their disease severity,appropriate treatment options,
educating and counselingthem and providing advocacy
and support for the patient.
And that can come in many fashions.
I think Christina mentioned earlier, a lot
of these patients are requesting,you know, letters for work

(44:13):
or potentially FMLA papers.
Although that can beburdensome to your time,
it really is something that is supporting
and advocating for thatpatient to get what they need.
The NP needs to take a holisticapproach to patient care
and build a therapeuticrelationship with their patient.
In addition, they have a responsibility
of working in this area to stay up to date
with the treatment guidelines

(44:34):
and the rapidly evolvingmedication landscape in order
to be able to provide the best
recommendations for their patients,
answer questions, addressconcerns, and give advice.
Christina, what resourcesare out there for APPs
regarding IBD if someone needs a reference
or wants to learn more?
- Yeah, absolutely andand I do think we do like

(44:55):
to practice guidelinebased evidence-based.
So I think practice guidelinesfrom the American College
of Gastroenterology and AGAcertainly are appropriate,
certainly are, you know, still valid
to reference even ifthey're not up to date
with these new therapeutic options.
But I still think that they serve a good purpose,
But I still think that they serve a good purpose,
especially in the primary caresetting when I don't expect

(45:17):
the nurse practitioner inthe primary care setting
to be necessarily initiating the therapy.
But certainly we'll have areally big role in monitoring
these patients and health maintenance.
So I think again, theAGA and ACG and,
and as I referenced earlier,
the AGA certainly hasupdated guidelines as
the AGA certainly hasupdated guidelines as
of last fall.
And as I mentioned earlier,
this newly publishedguideline on cancer screening

(45:39):
and vaccinations for our patientswith IBD through the AGA.
So it was called the AGAClinical Practice Update on Non
Colorectal CancerScreening
and Vaccinations in Patients with IBD.
And that was an expert review.
Again, I think that's a great resource.
And then I really find that the Crohn's
and Colitis Foundation reallyis an incredible resource
for both healthcare providers

(46:00):
and patients as well as their caregivers.
And you can access onlineat www.crohnscolitis
foundation.org.
And Jessica, I don't know ifyou have any other resources
that you reference yourpatients or caregivers to,
but I do tend to see the Crohn's
and Colitis Foundation
to be a really great resource.
- Yeah, Crohn's and Colitis Foundation
or CCFA is a really good resource.

(46:22):
It has sections both forpatients and providers.
Providers can also get a membership.
They have an annualconference, they have a lot
of medication guides
and things that make itreally easy for patients
to understand as well.
I also really love, youknow, the things that ACG
and AGA both have.
ACG has a really nice education universe

(46:42):
with a section specificto IBD
could be really great for anybody.
And then of course, GHAPP,
which is Gastroenterology and Hepatology
Advanced Practice Providers have a slew
of education on many things,
but they've done a few serieson the different IBD meds
and things like that thatare also very helpful.
Okay. Well I think that's all
that we have for today.

(47:03):
On behalf of myself, thank youso much for taking the time
to listen to this podcast.
I hope you learned something new today
and maybe have a new appreciation
for everything going on in theworld of ulcerative colitis.
- Yes, thanks everybody for tuning in
and thank you to AANP for having us on
for this fantastic podcast.
And Jessica, always a pleasureworking with you as well.

(47:24):
So thanks everybody for tuning in.
To our listeners, thank youfor visiting NP Pulse.
This podcast has been made possible
by a medication educationgrant provided by Janssen.
Continuing education creditfor this program may be claimed
through May 31st, 2026. To claim credit,
Login to the CE center at aanp.org/cecenter,

(47:50):
search for this program by name,
entering the participationcode COLITIS25.
That is C-O-L-I-T-I-S
25, and complete thepost-test and evaluation.
Be sure to download theUlcerative Colitis Clinical Brief
Companion Activity foradditional continued education,

(48:12):
pharmacology credit andinformation on this topic.