YEAR 1 PHARMD

INFLAMMATORY BOWEL DISEASE

(IBD)

Mariah Karen S. Calvario, RPh

Oksana M. Castillo, RPh
Raf Gregree L. David, RPh
Stephanie D. Gayeta, RPh
Ian Ray Van Matt Edward A. Guinid, RPh
Niña Angela P. Pamintuan, RPh
Emeliene Marie D. Rubenecia, RPh
Bea Trisha B. Tadena, RPh
INTRODUCTION
▪ Is an idiopathic disease caused by a dysregulated immune
response to host intestinal microflora
▪ Has two forms: Ulcerative Colitis (UC) and Crohn’s Disease (CD)
▪ UC: mucosal inflammatory condition confined
to the rectum and colon
▪ CD: transmural inflammation of the GI tract
that can affect any part, from the mouth to
the anus
EPIDEMIOLOGY

▪ Most prevalent in Western countries and in areas of

northern latitude

▪ Crohn’s Disease has an incidence of 6 to 15.5 cases per 100,000 persons

per year with a prevalence of 3.6 to 214 per 100,000 persons per year

▪ Ulcerative Colitis has an incidence of 1.2 to 20 cases per 100,000

persons per year with a prevalence of 7.6 to 246 per 100,000 persons
per year
ETIOLOGY
▪ Infectious Factors

▪ Genetic Factors

▪ Immunologic Mechanisms

▪ Psychological Factors

▪ Lifestyle, Dietary, and Drug-Related Causes

 INFECTIOUS FACTORS

▪ Microorganisms: major factor in the initiation of inflammation in IBD

▪ Viruses, protozoans, mycobacteria (Mycobacterium paratuberculosis
or avium), and other bacteria (Ruminococcus gnavus, Ruminococcus
torques, Listeria monocytogenes, Chlamydia trachomatis, Escherichia
coli)
▪ Bacterial gene products may promote alteration of the intestinal
barrier
▪ Bacterial antigens or ligands may include and propagate
inflammatory response
 GENETIC FACTORS
▪ Play a significant role in the predisposition to IBD

▪ First-degree relatives of patients with IBD may have up to a 20-fold increase in the risk of disease and
risk is extended to second and third-degree relatives
▪ Several genetic markers and loci have been identified that occur more frequently in patients with IBD,
however for UC genetics only explain 7.5% of disease variance
▪ Nucleotide-binding Oligomerization Domain protein 2 (NOD2), a key component involved in pathogen
recognition in the innate immune system, is the major contributor of genetic predisposition to CD
▪ Other genes involved in the innate immune system autophagy, such as ATG16L1 and IRGM, as well as
genes involved in the interleukin (IL) biologic pathway such as polymorphisms of the IL-23 receptor IL-
23R, and IL-12B, STAT3, and CCR6, are strongly associated with CD and possibly UC (IL23R)
▪ The major genetic region for UC is on chromosome 6p21, in the major histocompatibility region, near
human leukocyte antigen (HLA) class II genes
▪ An emerging area of interest in IBD pathogenesis is in the role of microRNAs, which are small
noncoding RNAs that regulate gene expression
 IMMUNOLOGIC MECHANISMS

▪ Plays a critical role in the pathogenesis of IBD

▪ Antineutrophil cytoplasmic antibodies are found in a high percentage
of patients with UC (70%) and less frequently in CD
▪ Dysregulation of cytokines is a key component of IBD
▪ Tumor necrosis factor-alpha (TNF-α) is a pivotal proinflammatory
cytokine that is increased in the mucosa and intestinal lumen of
patients with CD and UC
▪ TNF-α can recruit inflammatory cells to inflamed tissues, activate
coagulation, promote the formation of granulomas in patients with CD,
and possibly modify epithelial cell apoptosis
 PSYCHOLOGICAL FACTORS
▪ Mental health changes, particularly stress, appear to possibly
correlate with disease flares in IBD
▪ Rates of both pain, anxiety, and depression are higher in patients
with IBD compared to the general population, and are reported
in up to 19%-21% of patients
▪ Mood-related components, such as anxiety and depression, may
contribute to exacerbations of CD
▪ Approximately 50% of patients with IBD reported some type of
significant stress during any 3-month period
▪ May not be a direct cause of IBD, but may significantly affect
patient’s quality of life
 LIFESTYLE, DIETARY, AND DRUG-RELATED CAUSES
▪ Intake of refined sugars has been associated with development of CD, while
increased protein intake has been associated with a higher risk of developing IBD
▪ Diet composition and food derivatives may directly influence the makeup of the gut
microbiotica, alter intestinal permeability, and affect immune function possibly
triggering IBD
▪ Diets low in fermentable oligo-, di-, and monosaccharides and polyols, referred to as
FODMAPs, improve IBD symptoms in some patients by reducing the osmotic load
and fermentation of these sugars
▪ Use of nonsteroidal anti-inflammatory drugs (NSAIDs) may trigger disease
occurrence or lead to disease flares
▪ Antibiotics may induce Clostridium difficile infection, which is a cause of colitis
 CLINICAL AND PATHOLOGIC FEATURES OF
CROHN’S DISEASE AND ULCERATIVE COLITIS
 EXTRAINTESTINAL MANIFESTATIONS OF IBD

▪ Hepatobiliary Complications

▪ Joint Complications

▪ Ocular Complications

▪ Dermatologic and Mucocutaneous Complications

▪ Hematologic, Coagulation, Pulmonary, and Metabolic Abnormalities

 HEPATOBILIARY COMPLICATIONS

▪ Commonly found in patients with IBD

▪ Hepatic Complications: non-alcoholic fatty liver disease,

pericholangitis, autoimmune hepatitis, liver abscess, and cirrhosis

▪ Biliary Complications: Primary Sclerosing Cholangitis (PSC),

cholangiocarcinoma, and cholelithiasis
 JOINT COMPLICATIONS

▪ Both peripheral and axial arthropathies may be present

▪ Peripheral Arthritis: typically asymmetric, oligoarticular, non-

erosive, and occurs in 5% to 20% of patients

▪ Axial Arthropathies: include sacroiliitis, ankylosing spondylitis,

and IBD-associated spondyloarthropathy; prognosis is not as
favorable as peripheral arthritis, as progression is common
 OCULAR COMPLICATIONS

▪ Include dry eye, blepharitis, iritis, uveitis, episcleritis, and

conjunctivitis (29% of patients with IBD)

▪ Commonly reported symptoms with iritis and uveitis:

blurred vision, eye pain, and photophobia

▪ Episcleritis: associated with scleral injection, burning, and

increased secretions
 DERMATOLOGIC AND MUCOCUTANEOUS COMPLICATIONS

▪ Skin and Mucosal Lesions: erythema nodosum, pyoderma

gangrenosum, aphthous ulceration, and Sweet’s syndrome
▪ Oral lesions are found in 4% to 20% of patients with IBD

Sweet’s Syndrome (Acute Febrile Neutrophilic Dermatosis)

characterized by tender erythematous skin lesions secondary to
dermal neutrophil infiltration, and is often associated with fever and
a distribution on the upper trunk, face, neck, and arms
HEMATOLOGIC, COAGULATION, PULMONARY, AND METABOLIC ABNORMALITIES

▪ Anemia may present as iron deficiency related to chronic blood

loss, ongoing inflammation, malnutrition, hemolysis, or bone
marrow suppression from drug treatment
▪ Patients with IBD are at a 1.5 to 3.6 times higher risk of venous
thromboembolism (VTE) compared with the general population
▪ Patients with IBD may be at increased risk for metabolic bone
disease and development of osteoporosis
▪ Pulmonary manifestations occur from the glottis all the way to
the small airways, but most commonly involve the large airways
and may include interstitial pneumonia, bronchiectasis, and
bronchiolitis obliterans
IBD TREATMENT GOALS

▪ Resolution of acute inflammation and complications

▪ Alleviation of systemic manifestations

▪ Maintenance of remission

▪ Improvement in quality of life

ULCERATIVE COLITIS
INTRODUCTION

▪ Ulcerative colitis (UC) is confined to the rectum and colon,

causes continuous lesions, and affects primarily the mucosa and
the submucosa
▪ Unknown etiology
▪ Idiopathic inflammatory bowel disease that occurs more often in
industrialized countries
▪ Affects the colonic mucosa and is clinically characterized by
diarrhea, abdominal pain and hematochezia
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
NON-PHARMACOLOGIC

▪ Nutritional Support

▪ Surgery
MANAGEMENT
ALGORITHM
▪ Determining disease extent, that is, which sections of the colon are
involved, is important and accomplished via endoscopy
▪ “Proctitis” Inflammation confined to the rectal area
▪ Patients with “distal” disease have inflammation limited to areas
distal to the splenic flexure (also referred to as left-sided disease)
▪ Patients with “extensive disease” have inflammation extending
proximal to the splenic flexure
PHARMACOLOGIC
 MILD TO MODERATE (DISTAL)
▪ Topical mesalamine in an enema or suppository formulation is more
effective than oral mesalamine or topical steroids
▪ The combination of oral and topical mesalamine is more effective
than either alone for patients with left-sided or extensive disease
▪ Mesalamine preparations are typically better tolerated than
sulfasalazine and thus are often chosen preferentially as first-
line therapies
 MILD TO MODERATE (DISTAL)
&
MAINTENANCE OF REMISSION

▪ For patients with left-sided disease or proctitis, mesalamine enemas or suppositories are preferred
▪ The frequency of administration of topical agents may possibly be lessened to every third night over
time
▪ The combination of topical and oral mesalamine is superior to either regimen alone for maintenance
therapy
 MILD TO MODERATE (EXTENSIVE)
&
MAINTENANCE OF REMISSION

▪ For patients with extensive disease, oral once daily mesalamine is generally preferred at a dose of 2-3
grams/day
▪ The combination of oral and topical mesalamine is more effective than either alone for patients with
left-sided or extensive disease; however, patients may be less willing to use topical formulations.
▪ Controlled release budesonide (Uceris) is an alternative for mild to moderate extensive UC, while the
foam may be used for distal disease
 MODERATE TO SEVERE
▪ Oral 5-ASA products may be effective for moderately severe UC, however budesonide may be used as
alternative prior to use of more systemic corticosteroids and is preferred for moderate disease
▪ Systemic corticosteroids are often used in the treatment of moderate to severe active UC regardless of
disease location or in those patients who are unresponsive to maximal doses of oral and/or topical
mesalamine derivatives.
▪ TNF-α inhibitors is the main option for patients with moderate to severe disease who are
unresponsive to 5-ASAs or corticosteroids, or are corticosteroid dependent, and are more effective
than immunomodulator monotherapy for induction of remission
 MODERATE TO SEVERE
▪ Combining infliximab and azathioprine is more effective in inducing corticosteroid-
free remission in patients with acute severe colitis and is preferred
▪ Vedolizumab can be used for patients who fail immunomodulators and TNF-α
inhibitors, or as an alternative first line agent to TNF-α inhibitors.
▪ Vedolizumab should not be used in combination with TNF-α inhibitors but can be
combined with immunomodulators, such as azathioprine or methotrexate
 MODERATE TO SEVERE
▪ Systemic corticosteroids are used in the treatment of severe disease and may allow some patients to avoid colectomy
▪ IV hydrocortisone 300 mg daily in three divided doses or methylprednisolone 60 mg once daily is considered a first-line
agent
▪ Methylprednisolone is typically preferred due to its lesser mineralocorticoid effects.
▪ Unresponsive to parenteral corticosteroids after 3 to 7 days, have the option of receiving higher-potency agents such as
cyclosporine or infliximab
MODERATE TO SEVERE
 MAINTENANCE OF REMISSION
▪ Corticosteroids do not have a role in the maintenance of remission with UC because they
are ineffective and are associated with serious adverse effects with long-term use

▪ Azathioprine may be effective in preventing relapse of UC for patients who fail ASAs or who
are steroid dependent.

▪ Azathioprine is also recommended for patients with severe UC who are transitioned to oral
cyclosporine

▪ TNF-α inhibitors or vedolizumab are options for maintenance in patients with moderate to
severe UC following induction, and in those who are steroid dependent or have failed
azathioprine
CROHN’S DISEASE
INTRODUCTION

▪ Crohn’s disease is an idiopathic, chronic inflammatory process of

the gastrointestinal (GI) tract that can affect any part of the tract
from the mouth to the anus
▪ Individuals with this condition often experience periods of
symptomatic relapse and remission
▪ Approximately 30% of CD cases involve the small bowel,
particularly the terminal ileum, another 20% involve only the
colon, and 45% involve both the small bowel and colon
PATHOPHYSIOLOGY
 RISK FACTORS

▪ Family history
▪ Smoking
▪ Use of contraceptives and NSAIDs
▪ Diet
▪ Ethnicity
▪ Age
NON-PHARMACOLOGIC
NUTRITION
▪ Low residue or low-fiber diet to reduce the risk of intestinal blockage if there is a narrowed
bowel (stricture)
▪ Low residue diet is designed to reduce the size and number of stools
▪ Nutrition therapy short term and combine it with medications, such as immune system
suppressors
▪ Enteral and parenteral nutrition are typically used to get people healthier prior to surgery
or when other medications fail to control symptoms

SURGERY
▪ Remove a damaged portion of the digestive tract and then reconnects the healthy sections
▪ May also be used to close fistulas and drain abscesses
ASSESSING CROHN’S DISEASE SEVERITY
ASSESSING CROHN’S DISEASE SEVERITY
NEW DEFINITIONS ON DISEASE SEVERITY
MANAGEMENT
ALGORITHM
PHARMACOLOGIC
 MILD TO MODERATE
▪ Sulfasalazine is effective for treating symptoms of colonic
Crohn's disease that is mild to moderately active and can be used
as treatment for this patient population
▪ Oral mesalamine has not consistently been demonstrated to be
effective compared with placebo for induction of remission and
achieving mucosal healing in patients with active Crohn's disease
and should not be used to treat patients with active Crohn's
disease
 MILD TO MODERATE
▪ Controlled ileal release budesonide at a dose of 9 mg once daily
is effective and should be used for induction of symptomatic
remission for patients with mild-to-moderate ileocecal Crohn's
disease
 MILD TO MODERATE
▪ Metronidazole is not more effective than placebo as therapy for luminal inflammatory
Crohn's disease and should not be used as primary therapy
▪ Ciprofloxacin has shown similar efficacy to mesalamine in active luminal Crohn's disease
but has not been shown to be more effective than placebo to induce remission in Crohn's
disease and should not be used as therapy for luminal inflammatory Crohn's disease
▪ Antimycobacterial therapy has not been shown to be effective for induction or for
maintenance of remission or mucosal healing in patients with Crohn's disease and should
not be used as primary therapy
 MODERATE - SEVERE CROHN’S DISEASE — INDUCING
REMISSION

▪ Oral corticosteroids are effective and can be used for short-term

use in alleviating signs and symptoms of moderate to severely
active Crohn's disease
 MODERATE - SEVERE CROHN’S DISEASE
MAINTAINING INDUCED REMISSION

▪ ADDITION OF ANTI- TNF AGENTS AND THIOPURINES

▪ ANTI-TNF AGENTS ( INFLIXIMAB, ADALIMUMAB,
CERTOLIZUMAB)
▪ THIOPURINES ( AZATHIOPRINE OR 6-MERCAPTOPURINE )
 THIOPURINES — AZATHIOPRINE (PRODRUG OF
MERCAPTOPURINE) AND MERCAPTOPURINE

THIOPURINES
▪ effective in maintaining corticosteroid induced remission,
▪ slow acting, some serious side effects
 ANTI-TNF AGENTS - INFLIXIMAB, ADALIMUMAB,
CERTOLIZUMAB

Used to treat Crohn's disease that is resistant to treatment with corticosteroids, and for
Crohn's disease refractory to thiopurines or methotrexate. These agents are currently
reserved for resistant cases.
 INFLIXIMAB AS FIRST LINE THERAPY FOR INDUCING REMISSION

First Line Infliximab was superior to conventional treatment in achieving short-term clinical and endoscopic
remission, and had greater likelihood of maintaining clinical remission at week 52 on azathioprine
monotherapy.

However the guideline still recommends corticosteroids as first line, and that more studies would be needed
to support the use of Infliximab or other ANTI TNF as first line induction therapy.
 COMBINATION OF THIOPURINES AND ANTI-TNF AGENTS —
MAINTENANCE OF REMISSION

COMBINATION THERAPY IS PREFERRED OVER MONOTHERAPY

OF EITHER AGENTS
MAINTENANCE OF REMISSION — TAPER PREDNISONE
▪ IF THERE IS CLINICAL RESPONSE WITH THE AGENTS ADDED, YOU MAY TAPER
PREDNISONE AFTER 2-4 WEEKS
▪ IF THERE IS NO RESPONSE, YOU MAY CONSIDER SWITCHING THE ANTI TNF
AGENTS TO NATALIZUMAB OR VEDOLIZUMAB
HAS COMPARABLY SAME EFFICACY BUT VEDOLUZIMAB IS SAFER THAN
NATALIZUMAB
 SEVERE - FULMINANT CROHN’S DISEASE

▪ IV HYDROCORTISONE 100 mg — q 6h - 8h. Rule out infection before

initiating treatment

▪ CYCLOSPORINE IV 4 mg/kg/day — conflicting studies, New

guidelines from 2019 no longer includes use of Cyclosporine in this
case.

▪ INFLIXIMAB 5 mg/kg
IV HYDROCORTISONE 100 MG Q 6-8H
CYCLOSPORINE 4 MG/KG/DAY
INFLIXIMAB - 5 MG/KG
 SPECIAL CONSIDERATIONS
PREGNANCY AND BREASTFEEDING
▪ Greater risk of adverse pregnancy outcomes such as spontaneous abortion,
low birth weight, caesarian section, congenital abnormalities, low Apgar
scores, preterm rupture of membranes, and preeclampsia
▪ Most patients can conceive and have a normal pregnancy
▪ In patients in remission at the time of conception the rates of reported flares
are 20% in CD and 33% in UC, and postpartum rates of relapse are reported
as 14%
▪ Preconception counseling in patients with IBD is recommended, in addition
to objective assessment of disease activity in order to optimize therapy
▪ Diligence should be given to reviewing current medications in patients with
IBD who are both contemplating pregnancy or have already conceived
 REFERENCES
DiPiro, J., Yee, G., Posey, L.M., Haines, S., Nolin, T., &
Ellingrod, V. (2020). Pharmacotherapy: A
Pathophysiologic Approach (11th Edition). New
York, NY: McGraw-Hill Education.

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https://academic.oup.com/ecco-
jcc/article/8/3/200/528009

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC
4876845/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC
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THANK YOU!