Download Free Medical Gastroenterology-Inflammatory Bowel Disease PowerPoint Presentation

Gastroenterology-Inflammatory Bowel Disease PowerPoint Presentation

DOWNLOAD MEDICAL POWERPOINT PRESENTATION

About This Presentation

Description : Check out this medical PowerPoint presentation titled "Gastroenterology: Inflammatory Bowel Disease".

This medical PowerPoint presentation talks about Inflammatory Bowel Disease (IBD), a chronic condition that causes inflammation in the digestive tract. The two most common types of IBD are Crohns disease and ulcerative colitis.

Tags : inflammatory bowel diseases, digestive tract, Crohns disease, ulcerative colitis, abdominal pain, diarrhea, bloody stools, Digestive System, Digestive System PowerPoint presentation

Published on : Mar 28, 2023 | Views : 1286 | Downloads : 1

Shareable Url :

Embed Code :

Comment

Transcript

Slide 1-

Gastroenterology Inflammatory Bowel Disease
Slide 2-

Learning Objectives (Slide 1 of 3) Discuss the various etiologies of IBD that have been postulated Differentiate the major clinical and pathologic features ulcerative colitis and Crohn’s disease, and given these features be able to distinguish between the two List the common extraintestinal manifestations of IBD Identify the potential complications of Crohn’s disease and ulcerative colitis
Slide 3-

Learning Objectives (Slide 2 of 3) Given a patient’s clinical presentation, assess disease severity for ulcerative colitis and Crohn’s disease Discuss the therapeutic goals when treating patients with Crohn’s disease and ulcerative colitis Explain non-pharmacologic therapies used in the management of patients with IBD and their place their place in therapy Identify the major pharmacologic therapies for ulcerative colitis and Crohn’s disease
Slide 4-

Learning Objectives (Slide 3 of 3) Apply the various treatment approaches for IBD as related to disease severity, site of disease, and the need for acute or maintenance therapy Given an IBD patient history, recommend appropriate pharmacologic and nonpharmacologic therapies and support your recommendation with appropriate rationale Discuss drug adverse effects and monitoring parameters for drugs and disease states Construct counseling points for an IBD patient on their disease state and pharmacologic therapy (including proper administration)
Slide 5-

Required Reading Hemstreet BA. Chapter 34. Inflammatory Bowel Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e. New York, NY: McGraw-Hill; 2017.
Slide 6-

Overview IBD Definition: generic term for a group of chronic, idiopathic, relapsing inflammatory disorders of the gastrointestinal tract. Two forms of idiopathic IBD are: Ulcerative colitis (UC) Mucosal inflammatory condition that is limited to the rectum and colon Crohn’s disease (CD) Transmural inflammatory condition that can affect any part of the GI tract, from the mouth to the anus
Slide 7-

Epidemiology (Slide 1 of 2) Rates of IBD are highest in North America, Northern Europe, and Great Britain Ulcerative colitis (UC) Incidence: 8 – 12 cases per 100,000 per year in the U.S. Prevalence: 500,000 cases in the U.S. Crohn’s disease (CD) Incidence: 5 cases per 100,000 per year in the U.S. Prevalence: 50 cases per 100,000 in the U.S.
Slide 8-

Epidemiology (Slide 2 of 2) The peak incidence occurs in the second or third decade of life with a second peak occurring between the ages of 60 and 70 IBD affects both sexes somewhat equally overall 20% to 30% more woman are affected with CD Slightly more men (60%) are affected with UC Caucasians are affected more than non-whites for both UC and CD
Slide 9-

Etiology The exact etiology of IBD is unknown. It is postulated that the cause of IBD is a combination of: Infectious factors Genetic factors Immunologic mechanisms Environmental causes Psychological factors Lifestyle, Dietary, and drug-related causes
Slide 10-

Infectious Factors Microorganisms are a proposed major factor in the initiation of inflammation in IBD, but no one definitive infectious cause of IBD has been found Microorganisms such as viruses, protozoans, and mycobacteria may promote alteration of the intestinal barrier and/or propagate an inflammatory response
Slide 11-

Genetic Factors Genetic factors play a significant role in the predisposition to IBD First-degree relatives of patients with IBD have a 20-fold increase in the risk of the disease Identical twins have a concordance rate of IBD in both individuals, particularly with CD
Slide 12-

Immunologic Mechanisms The immune system plays a critical role in the pathogenesis of IBD and include both autoimmune and non-autoimmune phenomena The inflammatory response may indicate an abnormal regulation of the normal immune response or an autoimmune reaction to self-antigens In both UC and CD, the bowel mucosa is infiltrated with lymphocytes, plasma cells, macrophages, and neutrophils IBD responds to immunosuppressive agents Many of the extraintestinal manifestations (presented on slides 20 - 26) have an immunologic component
Slide 13-

Environmental Causes (Slide 1 of 3) Psychological Factors Mental heath changes, such as stress, appear to correlate to disease flares in IBD However, psychological factors as true etiologic factors in the pathogenesis if IBD is unclear Dietary Factors Theories on the influence of diet and the development of IBD have been proposed, as diet composition may influence the makeup of the gut microbiotica Intake of refined sugars has been associated with the development of CD Increased protein intake has been associated with a higher risk of developing IBD
Slide 14-

Environmental Causes (Slide 2 of 3) Smoking Smoking plays an important but contrasting role in CD and UC Smoking appears to be protective in UC and is associated with fewer disease flare-ups and reduced disease severity Smoking cessation should be encouraged for all patients, including those with UC In CD, smoking is associated with increased disease frequency and severity
Slide 15-

Environmental Causes (Slide 3 of 3) There may be an association between the use of certain medications and the development of IBD Nonsteroidal antiinflammatory drugs (NSAIDs) Antibiotics Oral contraceptives Isotretinoin Direct causal relationships remain unclear
Slide 16-

Ulcerative Colitis (UC) Pathophysiology UC is confined to the rectum and colon Lesions affect the mucosal and submucosal layers In UC, the mucosal appearance includes edema, mucopus, erosions, and the lesions are continuous in nature Lesions are sometimes referred to as having an “lead pipe” appearance Fistulas, strictures, perforations are rare
Slide 17-

Crohn’s Disease (CD) Pathophysiology CD is characterized by a transmural inflammatory process Lesions can occur anywhere in the GI tract but the terminal ileum is the most common site In CD, the mucosal appearance often includes ulcers, strictures, fistulas and the lesions are discontinuous and segmented Lesions are sometimes said to give a “cobblestone” appearance Fistulas and strictures are common Nutritional deficiencies are common
Slide 18-

Inflammatory Bowel Disease (IBD) Pathophysiology Link: Table on Comparison of Clinical and Pathologic Features of Crohn’s Disease and Ulcerative Colitis Link: Figure of Ulcerative Colitis Link: Figure of Colonoscopy with Acute Ulcerative Colitis Link: Figure of Crohn’s Disease of the Colon Link: Figure of Wireless Capsule Endoscopy Image in a Patient with Crohn’s Disease of the Ileum
Slide 19-

Extraintestinal Manifestations of IBD Both UC and CD are associated with the development of symptoms and organ involvement outside of the GI tract and these are referred to as extraintestinal manifestations Several of these have immunologic components associated with them Extraintestinal manifestations include hepatobiliary complications; joint complications; ocular complications; dermatologic complications; hematologic, coagulation, and metabolic abnormalities
Slide 20-

Hepatobiliary Complications Approximately 11% of UC patients have hepatobiliary complications with overall frequencies ranging from 5% to 95% Hepatic complications include: fatty liver, pericholangitis, autoimmune hepatitis, and cirrhosis Biliary complications include: primary sclerosing cholangitis, cholangiocarcinoma, and cholelithiasis
Slide 21-

Joint Complications Arthritis in IBD is typically asymmetric and migratory involving one or few usually large joints Arthritis severity parallels IBD disease activity Arthritis can include sacroiliitis, ankylosing spondylitis, and IBD-associated spondyloarthropathy
Slide 22-

Ocular Complications Occurs in 2% to 29% of patients with IBD Ocular complications include iritis, uvetitis, episcleritis, conjunctivitis
Slide 23-

Dermatologic Complications Skin and mucosal lesions associated with IBD include erythema nodosum, apthous ulcers, pyoderma gangrenosum, and Sweet’s syndrome Erythema nodosum occurs in 2% to 20% of IBD patients Pyoderma gangrenosum occurs in 0.5% to 2% of IBD patients Oral lesions occur in 4% to 20% of IBD patients
Slide 24-

Hematologic, Coagulation, and Metabolic Abnormalities (Slide 1 of 2) Prevalence of anemia in IBD patients is up to 74% Anemia may present at iron deficiency due to chronic blood loss, inflammation, malnutrition, hemolysis, or bone marrow suppression from drug therapy Anemia may present as anemia of chronic disease secondary to chronic inflammation and overproduction of cytokines
Slide 25-

Hematologic, Coagulation, and Metabolic Abnormalities (Slide 2 of 2) Patients with IBD are at 1.5 to 3.6 times higher risk of venous thromboembolism (VTE) compared with the general population This is secondary to activation of the clotting cascade and platelet activation due to inflammation Patients with IBD are at increased risk of metabolic bone disease and the development of osteoporosis Most likely due to a combination of nutritional deficiencies (e.g. calcium and vitamin D), chronic cytokine-related inflammatory response on bone, disease-associated hypogonadism, and use of corticosteroids
Slide 26-

Clinical Presentation of IBD Presenting symptoms common to both UC and CD include: Diarrhea Abdominal cramping Fever Rectal bleeding Weight loss Most people with IBD have periods of exacerbations and remissions
Slide 27-

UC Clinical Presentation (Slide 1 of 6) There is a wide range of presentation in UC There is no standard disease severity scoring system The arbitrary distinctions of mild, moderate, severe, and fulminant disease activity are generally accepted and used in treatment guidelines These classifications are determined by clinical signs and symptoms
Slide 28-

UC Clinical Presentation (Slide 2 of 6) Mild Less than 4 stools per day, with or without blood, with no systemic disturbance and a normal erythrocyte sedimentation rate (ESR) Moderate Four or more stools per day but with minimal systemic disturbance
Slide 29-

UC Clinical Presentation (Slide 3 of 6) Severe More than 6 stools per day with blood and systemic disturbance Fulminant More than 10 stools per day with continuous bleeding that may require transfusion, abdominal tenderness, colonic dilation, and additional marked systemic disturbance/toxicity
Slide 30-

UC Clinical Presentation (Slide 4 of 6) Systemic disturbance includes: Fever (temperature > 99.5 degrees Fahrenheit) Tachycardia (HR > 90 bpm) Anemia (hemoglobin < 75% of normal) ESR > 30 mm/h Abdominal tenderness Bowel wall edema
Slide 31-

UC Clinical Presentation (Slide 5 of 6) In addition to determining disease severity, determining disease extent or which parts of the colon are involved is important Distal disease (AKA left-sided disease) – inflammation limited to areas distal to the splenic flexure Extensive colitis – inflammation extending proximal to the splenic flexture Proctitis – inflammation confined to the rectum Proctosigmoiditis – inflammation involving the rectum and sigmoid colon Pancolitis – inflammation occurring in the majority of the colon
Slide 32-

UC Clinical Presentation (Slide 6 of 6) Link: Table on Clinical Presentation of Ulcerative Colitis Link: Table on Ulcerative Colitis: Disease Presentation
Slide 33-

CD Clinical Presentation (Slide 1 of 6) Presentation of CD is highly variable Global classification guidelines for scoring CD are not available The Crohn’s Disease Activity Index (CDAI) is used most often to gauge response to therapy, determine remission, and is employed mostly in the research setting Scores range from 0 to 600 with a score greater than 150 defined as active disease Link to CDAI: http://www.ibdjohn.com/cdai/ The Harvey Bradshaw Index (HBI) is another CD scoring system that correlates well with the CDAI. A decrease of 3 points in the HBI is defined as a clinical response with complete remission defined as a score of < 4 Link to HBI: http://www.e-guide.ecco-ibd.eu/resource/hb-index
Slide 34-

CD Clinical Presentation (Slide 2 of 6) Treatment guidelines use the presence of signs and symptoms as their marker for disease activity and severity The primary classifications used are: Mild to Moderate disease Moderate to Severe disease Severe to Fulminant disease
Slide 35-

CD Clinical Presentation (Slide 3 of 6) Mild to Moderate Disease Ambulatory patients who are able to tolerate food and beverage intake Absence of fever, dehydration, systemic toxicity, abdominal tenderness, mass, obstruction No weight loss or a non-significant weight loss Less than 10% of body weight Usually corresponding to a CDAI of 150 - 220
Slide 36-

CD Clinical Presentation (Slide 4 of 6) Moderate to Severe Disease Those who fail to respond to treatment for mild/moderate disease OR Those with more prominent symptoms such as fever, abdominal pain/tenderness, intermittent nausea/vomiting, dehydration, significant weight loss, significant anemia Usually corresponding to a CDAI of 220 - 450
Slide 37-

CD Clinical Presentation (Slide 5 of 6) Severe to Fulminant Disease Those with persistent symptoms despite the use of corticosteroid or biologic treatment OR Those with high fever, persistent vomiting, rebound tenderness, cachexia, evidence of intestinal obstruction or abscess Usually corresponding to a CDAI > 450
Slide 38-

CD Clinical Presentation (Slide 6 of 6) Link: Table on Clinical Presentation of Crohn’s Disease
Slide 39-

Selected Complications Toxic Megacolon IBD patients are at increased risk of developing toxic megacolon, which is a segmental or total colonic distension of greater than 6cm with acute colitis and signs of systemic toxicity Colon Cancer IBD patients are at higher risk of colorectal carcinoma (CRC) Risk factors for CRC include: young age at IBD onset (<50 years old), severe inflammation, positive family history of CRC, presence of primary sclerosing cholangitis, or inflammatory polyps Screening colonoscopy should be performed at 8 years after onset of IBD symptoms with subsequent screenings every 1 to 2 year if negative
Slide 40-

IBD Diagnosis The diagnosis of IBD is made on clinical suspicion confirmed by a thorough medical evaluation using: Sigmoidoscopy or colonoscopy Biopsy Stool examinations Barium radiographic contrast studies Laboratory testing The presence of extraintestinal manifestations may also aid in establishing a diagnosis
Slide 41-

Goals of Therapy in IBD IBD is a chronic lifelong illness characterized by exacerbations and periods of remission. As no specific therapy exists, current treatment is directed toward symptomatic improvement and controlling the disease process. Goals of therapy include: Provide relief of symptoms (induce remission) Improve quality of life Maintain adequate nutritional status Relieve intestinal inflammation Decrease frequency of recurrence Resolve complications
Slide 42-

Nonpharmacologic Therapy: Nutritional Support (Slide 1 of 4) Proper nutritional support is an important aspect in the treatment of patients with IBD because patients with moderate to severe disease are often malnourished either because the inflammatory process results in significant malabsorption or maldigestion because of the catabolic effects of the disease process. Many specific diets have been tried to improve nutritional status and symptoms of IBD but none has gained widespread acceptance In general, individual patients can try avoiding specific foods that may exacerbate their symptoms
Slide 43-

Nonpharmacologic Therapy: Nutritional Support (Slide 2 of 4) Nutritional needs of patients with IBD may be adequately addressed with enteral supplementation in acute or chronic situations Parenteral nutrition has a more limited role in IBD and is reserved for patients with severe malnutrition or those who fail enteral therapy
Slide 44-

Nonpharmacologic Therapy: Nutritional Support (Slide 3 of 4) Intestinal microbiotica play a key role in IBD pathogenesis and so probiotics as adjunctive therapy in IBD has been explored Postulated mechanisms supporting the use of probiotics in IBD include Reestablishment of normal bacterial flora in the gut Reduction in bacterial adhesion and competition for nutrients with pathogenic bacteria Production of antibacterial substances Promotion of favorable effects on the host immune response
Slide 45-

Nonpharmacologic Therapy: Nutritional Support (Slide 4 of 4) Probiotic therapy involves the reestablishment of normal bacterial flora within the gut by oral administration of live bacteria such as nonpathogenic Escherichia coli, bifodbaceria, lactobacilli, Streptococcus thermophilus, Saccharomyces boulardii Probiotics have demonstrated some effectiveness in inducing and maintaining remission in some trials for patients with UC Evidence of probiotic use in the induction and maintenance of CD is less compelling and has led to recommendations not supporting widespread use
Slide 46-

Nonpharmacologic Therapy: Surgery Even with many medications available to treat IBD, many patients will require surgery Surgical procedures may involve resection of segments of intestine that are affected, correction of complications (e.g., fistulas, strictures, obstructions, perforations, etc.), or drainage of abscesses
Slide 47-

Pharmacologic Agents Used in the Treatment of IBD Aminosalicylates Corticosteroids Immunomodulators Tumor necrosis factor (TNF)-inhibitors and other biologics Miscellaneous agents Link: Figure on Proposed Pathogenesis of Inflammatory Bowel Disease and Target Sites for Pharmacologic Intervention
Slide 48-

Aminosalicylates (Slide 1 of 6) MOA Not completely understood but postulated to diminish inflammation by inhibiting cyclooxygenase and lipoxygenase, thereby decreasing prostaglandins, leukotrienes, and HETEs resulting in decreased inflammation Agents Sulfasalazine (Azulfidine) Mesalamine Suppository (Canasa) Enema (Rowasa) Oral formulations Asacol and Asacol HD Apriso Lialda Pentasa Delzicol Olsalazine (Dipentum) Balsalazide (Colazal)
Slide 49-

Aminosalicylates (Slide 2 of 6) Common adverse effects GI disturbances, headache, arthalgia, rash Serious adverse effects Hepatotoxicity, blood dyscrasias, renal impairment Monitoring Sulfasalazine: Liver function tests, CBC with differential, renal function tests prior to starting therapy; every 2 weeks for the 1st 3 months; every month during months 4, 5, and 6; every 3 months thereafter or as clinically indicated Other Aminosalicylates: CBC with differential (particularly in elderly patients), liver function tests, renal function tests prior to starting therapy; 6 weeks after initiation; at 3 months and then periodically or as clinically indicated
Slide 50-

Aminosalicylates (Slide 3 of 6) Patient Counseling Sulfasalazine Serious and potentially life threatening skin and/or hypersensitivity reactions may occur, especially during the first month of therapy May cause the urine/skin to turn a yellow-orange color Maintain adequate hydration to prevent renal stone formation Take in evenly divided doses after meals All aminosalicylates Delayed-release tablets should be swallowed whole Advise patients to report signs/symptoms of renal failure
Slide 51-

Aminosalicylates (Slide 4 of 6) Sulfasalazine Prototype aminosalicylate The drug is cleaved by colonic bacteria to an active portion (5-aminosalicylate or 5-ASA) and an inactive carrier molecule (sulfapyridine) AVOID in patients with a SULFA allergy Mesalamine Available in various formulations including a rectal suppository, enema, and various oral formulations that release the drug at different points in the GI tract
Slide 52-

Aminosalicylates (Slide 5 of 6) Olsalazine A dimer of two 5-ASA molecules linked by an azo bond Mesalamine is released in the colon after colonic bacteria cleave the azo bond High incidence of diarrhea as an adverse effect (up to 25% of patients) Balsalazide A mesalamine prodrug that couples mesalamine with an inert carrier molecule and is enzymatically cleaved in the colon to release mesalamine
Slide 53-

Aminosalicylates (Slide 6 of 6) Different aminosalicylate products have different sites of action and hence location of the disease in the GI tract is factored into the selection of an agent Suppositories have local activity in the rectum and are useful in proctitis Enemas have local activity in the rectum and distal colon and are useful to treat left-sided disease Different oral formulations release drug at different points in the small intestine and colon Link: Figure on Site of Activity of Various Agents Used to Treat Inflammatory Bowel Disease
Slide 54-

Corticosteroids (Slide 1 of 6) MOA Decreases inflammation by suppression of migration of polymorphonuclear leukoctyes and reversal of increased capillary permeability; suppresses the immune system by reducing activity and volume of the lymphatic system Agents Prednisone (Deltasone) Prednisolone Methylprednisolone (Medrol) Hydrocortisone Budesonide (Entercort EC, Uceris)
Slide 55-

Corticosteroids (Slide 2 of 6) Common adverse effects Hypertension, body fluid retention, impaired glucose tolerance, increased appetite, weight gain, osteoporosis, disturbance in mood Serious adverse effects Cushing’s syndrome, impaired wound healing, bone fracture, tendon rupture, cataract formation, psychotic disorder, pulmonary edema, increased infection risk
Slide 56-

Corticosteroids (Slide 3 of 6) Monitoring Blood pressure, electrolyte panel, blood glucose, mental status Signs and symptoms of infection With prolonged therapy Ophthalmic exam Hypothalamic-pituitary-adrenal (HPA) axis suppression tests Urinalysis, blood glucose, blood pressure, weight, chest X-ray at regular intervals
Slide 57-

Corticosteroids (Slide 4 of 6) Patient Counseling Advise to take with food or milk to minimize GI upset Patient should report signs and symptoms of infection and adrenocortical insufficiency Advise diabetes patients to report problems with glycemic control Consult health care provider prior to receiving vaccines Corticosteroid therapy beyond 2 weeks may cause immunosuppression, which is a concern with live vaccines
Slide 58-

Corticosteroids (Slide 5 of 6) Corticosteroids work very quickly to suppress inflammation and reduce flare-ups Corticosteroids should NOT be used for maintenance therapy Budesonide has a high ratio of local anti-inflammatory to systemic effect due to an extensive first pass metabolism Administered orally in a controlled-release formulation designed to release in the terminal ileum or the colon depending on the product This results in a decrease in systemic effects and systemic adverse effects
Slide 59-

Corticosteroids (Slide 6 of 6) In addition to oral and IV formulations, hydrocortisone is also available as a(n): Suppository (Anucort, Proctocort) Enema (Cortenema) Foam (Cortifoam)
Slide 60-

Patient Counseling for Mesalamine and Hydrocortisone Enema Administration An enema is a procedure introducing liquid into the rectum and colon through the anus Enemas are most commonly used as laxatives to relieve constipation or to deliver medication to the rectum and colon for inflammatory bowel disease
Slide 61-

How to Use an Enema Shake to mix (particularly mesalamine and hydrocortisone enemas because they are suspensions) Remove the cap/cover from the applicator tip Hold the bottle at the neck so you don’t accidently squeeze out any medication
Slide 62-

How to Use an Enema (Administration) Get into appropriate position (either of the following positions) Lie on the floor on left side with right knee bent This is the most comfortable position and hence the one most patients prefer Lie on floor on stomach and then bring both knees to chest Gently insert the applicator tip into the rectum, pointing it slightly toward your navel Most manufactured enemas have a lubricated tip. However, patients can apply petroleum jelly to the anus prior to enema insertion, if desired. Grasp the bottle firmly, then tilt slightly so that the nozzle is aimed toward the back, squeeze slowly to instill the medication. Steady hand pressure will discharge most of the medication After administering, withdraw bottle and discard when able to do so
Slide 63-

How to Use an Enema (Enema Retention) How long the patient remains in position and/or retains the contents of the enema depends on the active ingredient in the enema For enemas used for IBD, specifically mesalamine and hydrocortisone enemas, it is recommended to Remain in the position the enema was administered in for at least 30 minutes to allow the thorough distribution of the medication Retain the enema all night (preferably 8 hours), if possible Hence, these enemas are typically administered at bedtime
Slide 64-

Additional Patient Counseling Enemas can cause staining of direct contact surfaces including fabrics, painted surfaces, marble, granite, vinyl, and enamel. Consider this when choosing the location for administration Mesalamine enema suspensions are off-white to tan in color. Contents of enemas removed from the foil pouch may darken with time. Slight darkening will not affect potency, however, enemas with dark brown contents should be discarded If the patient has difficulty retaining a mesalamine or hydrocortisone enema, he/she can administer half of the bottle and then administer the second half in 1 hour.
Slide 65-

Immunomodulators MOA Immunosuppressive actions through a variety of mechanisms Agents Azathioprine (Imuran, Azasan) Mercaptopurine (Purinethol) Methotrexate (Trexall) Cyclosporine (Gengraf, Neoral, Sandimmune) Additional information depending on the specific agent
Slide 66-

Azathioprine (AZA) and Mercaptopurine (6-MP) (Slide 1 of 2) Are effectively used in long-term treatment of both UC and CD Generally reserved for patients who fail 5-ASA therapy or are refractory to or dependent on corticosteroids May be used in conjunction with 5-ASAs, corticosteroids, and TNF-inhibitors TPMT (thiopurine methyltransferase) is partially responsible for the metabolism of AZA and 6-MP. Genotype/phenotype prior to initiation in order to determine enzyme activity and properly dose (especially concerned with bone marrow, hepatic, and renal toxicity)
Slide 67-

Azathioprine (AZA) and Mercaptopurine (6-MP)(Slide 2 of 2) Are indicated for IBD maintenance therapy due to a long onset of action Onset of action can range from a few weeks to up to 12 months before benefits are seen Adverse reactions: pancreatitis, bone marrow suppression, anemia, thrombocytopenia, hepatotoxicity, renal toxicity, nausea, diarrhea, rash Monitoring: CBC w/diff and platelets weekly for 1 month, biweekly for 1 month, then every 1 to 2 months; LFTs and renal function every 1 – 2 weeks for 1st month then every 3 months thereafter
Slide 68-

Methotrexate (MTX) Useful for the treatment and maintenance of CD; data supporting use in UC is lacking Adverse reactions: reddening of skin, hyperuricemia, GI adverse effects, leukopenia, myelosuppression, thrombocytopenia, renal failure, nephropathy, immunosuppression, cirrhosis Monitoring: CBC w/ diff and platelets, Scr, LFTs (baseline then every 2 to 4 weeks for first 3 months then every 8-12 weeks for 3-6 months of therapy, then every 12 weeks after 6 months of therapy); chest x-ray (baseline); PFTs (if MTX induced lung disease suspected); hepatitis B and C testing (baseline)
Slide 69-

Cyclosporine Used in severe flares of IBD not responding to IV corticosteroids Poses a risk of nephrotoxicity and neurotoxicity Adverse reactions: hypertension, headache, renal dysfunction, GI adverse effects, hepatotoxicity, leukopenia, anemia, thrombocytopenia, infection Monitoring: Blood pressure, renal function, liver function, and CBC with differential
Slide 70-

Tumor Necrosis Factor (TNF) Inhibitors (Slide 1 of 4) MOA Inhibits endogenous TNFα. Elevated levels of TNFα have been found in involved tissues of various disease states including CD and UC. Biological activities of TNFα include the induction of proinflammatory cytokines, enhancement of leukocyte migration, activation of neutrophils and eosinophils, and the induction of acute phase reactants and disease degrading enzymes. Agents Infliximab (Remicade) and Infliximab-dyyb (Inflectra) Adalimumab (Humira) and Adalimumab-atto (Amjevita) Certolizumab (Cimzia) Golimumab (Simponi)
Slide 71-

Tumor Necrosis Factor (TNF) Inhibitors (Slide 2 of 4) Common adverse effects Rash, abdominal pain, nausea, headache, cough, upper respiratory tract infection, fatigue Serious adverse effects Hepatotoxicity, anemia, leukopenia, neutropenia, tuberculosis, increase infections
Slide 72-

Tumor Necrosis Factor (TNF) Inhibitors (Slide 3 of 4) Black Box Warnings Serious infections: Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis) and infections due to other opportunistic pathogens. Discontinue infliximab if a patient develops a serious infection. Perform test for latent TB; if positive, start treatment for TB prior to starting infliximab. Monitor all patients for active TB during treatment, even if initial latent TB test is negative. Increased risk of lymphoma and other malignancies: Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with tumor necrosis factor (TNF) blockers, including infliximab. Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers including infliximab. Almost all had received azathioprine or 6-mercaptopurine concomitantly with a TNF-blocker at or prior to diagnosis. The majority of infliximab cases were reported in patients with Crohn’s disease or ulcerative colitis, most of whom were adolescent or young adult males
Slide 73-

Tumor Necrosis Factor (TNF) Inhibitors (Slide 4 of 4) Monitoring Monitoring for effectiveness: Reduction in signs and symptoms of disease, clinical remission, mucosal healing, elimination of corticosteroid use Monitoring for safety: Latent TB screening prior to initiating therapy and during therapy; signs and symptoms of infection; CBC with differential; signs and symptoms of heart failure, HBV screening prior to initiating; LFTs (discontinue if > 5 times ULN); signs and symptoms of malignancy
Slide 74-

TNF-Inhibitors: Infliximab (Slide 1 of 2) Infliximab (Remicade) and its biosimilar product Infliximab-dyyb (Inflectra) A chimeric (human/mouse) IgG monoclonal antibody that binds to and inhibits TNFα Indicated for both CD and UC Moderate to severe active disease Maintenance therapy in moderate to severe disease Fistulizing disease
Slide 75-

TNF-Inhibitors: Infliximab (Slide 2 of 2) Dose and administration 5mg/kg given as an IV infusion over 2 hours repeated at weeks 2 and 6; maintenance dose of 5 mg/kg every eight weeks (10 mg/kg if response diminished to 5 mg/kg) Therapeutic serum concentrations persist for about 8 weeks.
Slide 76-

TNF-Inhibitors: Adalimumab Adalimumab (Humira) and its biosimilar product Adalimumab-atto (Amjevita) Indications: Moderate to severe CD and UC refractory to conventional treatment Dose and administration: 160 mg SUBQ at week 0 (may administer as 4 injections in 1 day or 2 injections daily for 2 consecutive days), 80 mg SUBQ at week 2, then 40 mg SUBQ every other week starting at week 4
Slide 77-

TNF-Inhibitors: Certolizumab Certolizumab (Cimzia) Indication: Moderate to severe CD refractory to conventional treatment Dose and administration: 400mg SUBQ injection every 2 weeks for the first 3 injections (weeks 0, 2, 4) and then every 4 weeks for maintenance therapy in patients who demonstrate a response
Slide 78-

TNF-Inhibitors: Golimumab Golimumab (Simponi) Indication: Induction and remission of moderate/severe UC in patients with corticosteroid dependence or who are refractory or intolerant to aminosalicylates, corticosteroids, azathioprine, or 6-mercaptopurine Dose and administration: 200mg SQ week 0, then 100mg SQ at week 2, then 100mg every 4 weeks thereafter
Slide 79-

Additional Information Patient education Counsel patient on the increased risk of infection and to report signs/symptoms of an infection or a recurring infection Advise patient of increased risk of lymphoma and other malignancies Warn patient to avoid live vaccines during therapy due to drug-induced immunosuppression. Side effects may include upper respiratory infections, hypertension, rash, dizziness Advise patient to report symptoms of new or worsening congestive heart failure Counsel patient about proper injection sites and rotation if administering subQ
Slide 80-

Other Biologics: Natalizumab (Slide 1 of 3) Natalizumab (Tysabri) MOA A humanized monoclonal antibody that targets integrin molecules expressed on the cell surface of leukocytes. Integrins bind to vascular receptors in the gut, allowing leukocytes to migrate across the vacular endothelium. Natalizumab blocks this process and inhibits the inflammatory cascade. Indication: Induction and maintenance treatment of CD refractory to conventional therapies and TNF inhibitors. Dose and administration: 300 mg IV over approximately 1 hr, repeat every 4 weeks (28 days); discontinue therapy for lack of therapeutic benefits by 12 weeks after initiation of therapy
Slide 81-

Other Biologics: Natalizumab (Slide 2 of 3) Adverse effects: headache, fatigue, depression, rash, GI effects, infection, hepatotoxicity Black Box Warning Natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML), which may lead to death or severe disability. Risk factors for PML include therapy duration, prior immunosuppressant use, and presence of anti-JC virus antibodies. Because of the risk of PML, natalizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH(R) Prescribing Program.
Slide 82-

Other Biologics: Natalizumab (Slide 3 of 3) Monitoring Baseline brain MRI Monitor patients for any new sign or symptom that may be suggestive of PML and interrupt therapy at the first sign or symptom suggestive of PML. For diagnosis, a gadolinium-enhanced MRI scan of the brain and, if indicated, cerebrospinal fluid analysis for JC viral DNA are recommended Signs and symptoms of infection LFTs and signs and symptoms of liver injury
Slide 83-

Other Biologics: Vedolizumab (Slide 1 of 2) Vedolizumab (Entyvio) MOA reduces chronically inflamed gastrointestinal parenchymal tissue associated with ulcerative colitis and Crohn disease by binding specifically to the alpha-4-beta-7-integrin receptor and blocking its interaction with mucosal addressin cell adhesion molecule-1. This inhibits the movement of memory T-lymphocytes across the endothelium into inflamed gastrointestinal tissue Indications: Induction and maintenance in adults with moderate to severe active UC and CD who have had an inadequate response with, lost response to, or were intolerant to a TNF inhibitor or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids. Dose and administration: 300mg IV infusion at 0, 2, and 6 weeks then every 8 weeks
Slide 84-

Other Biologics: Vedolizumab (Slide 2 of 2) Common adverse effects: Nausea, arthralgia, headache, nasopharyngitis, upper respiratory infection, fatigue, fever Serious adverse effects: Hypersensitivity reaction, infusion reaction, infectious disease, tuberculosis, PML Monitoring: Hypersensitivity reactions and infusion reactions TB screening Sign and symptoms of PML
Slide 85-

Agents for the Treatment of IBD Link: Table on Agents for the Treatment of Inflammatory Bowel Disease Link: Table on Drug Monitoring Guidelines Link: Table on Medications Commonly Used to Treat Inflammatory Bowel Disease
Slide 86-

Pharmacotherapy for IBD Treatment selection is dependent on the Type (UC or CD) Severity (mild, moderate, severe, fulminant) Site of disease (proctitis, distal disease, extensive disease, small intestine involvement, etc.) Need for acute treatment or maintenance therapy
Slide 87-

UC Pharmacotherapy Proctitis – inflammation confined to the rectum Topical therapy used most often Distal disease (AKA left-sided disease) – inflammation limited to areas distal to the splenic flexure May use either systemic or topical therapy or a combination Extensive colitis – inflammation extending proximal to the splenic flexure Must use systemic therapy. May add topical therapy to systemic therapy if needed/appropriate Pancolitis – inflammation occurring in the majority of the colon Must use systemic therapy. May add topical therapy to systemic therapy if needed/appropriate
Slide 88-

Mild/Moderate DISTAL UC (Slide 1 of 2) Treatment of ACTIVE Disease First-line therapy: topical (enema/suppository) aminosalicylates If inadequate or no response to #1, use an oral aminosalicylate or topical corticosteroid May combine oral and topical aminosalicylates
Slide 89-

Mild/Moderate DISTAL UC (Slide 2 of 2) Remission/Maintenance Therapy: Mesalamine suppository or enema used 3 times per week OR Oral aminosalicylate tapered to a maintenance dose Topical or oral corticosteroids have no role in maintenance therapy
Slide 90-

Mild/Moderate EXTENSIVE UC (Slide 1 of 2) Treatment of ACTIVE Disease First-line therapy: Oral aminosalicylate If #1 doesn’t work, use budesonide 9mg/day for up to 8 weeks
Slide 91-

Mild/Moderate EXTENSIVE UC (Slide 2 of 2) Remission/Maintenance Therapy Preferred: Oral aminosalicylate If used budesonide for induction, then budesonide 6mg/day for up to 3 months plus oral aminosalicylate at maintenance dose
Slide 92-

Moderate/Severe UC (Slide 1 of 2) Treatment of ACTIVE disease First-line therapy: Oral aminosalicylate PLUS prednisone 40-60mg/day If inadequate or no response to #1, ADD azathioprine, mercaptorpurine, infliximab, adalimumab, or golimumab
Slide 93-

Moderate/Severe UC (Slide 2 of 2) Remission/Maintenance Therapy Taper prednisone, then after 1 to 2 months reduce oral aminosalicylate dose to maintenance dose Continue azathioprine, mercaptopurine, infliximab, adalimumab, or golimumab if previously added
Slide 94-

Severe/Fulminant UC (Slide 1 of 2) Treatment of ACTIVE disease 7 to 10 day course of intravenous corticosteroids (hydrocortisone) Patients refractory to IV corticosteroids (no response in 5 to 7 days) are candidates for IV cyclosporine
Slide 95-

Severe/Fulminant UC (Slide 2 of 2) Remission/Maintenance Therapy If remission achieved with IV hydrocortisone: Change IV hydrocortisone to oral prednisone and ADD azathioprine, mercaptopurine, adalimumab, or golimumab. Attempt to withdraw prednisone after 1 – 2 months. Can also consider adding oral aminosalicylate into the mix. If corticosteroid refractory disease and needed cyclosporine to achieve remission: Change IV cyclosporine to oral cyclosporine and ADD either azathioprine or mercaptopurine. May consider TNF-inhibitor at maintenance dose in the future, but if using oral cyclosporine, must use azathioprine or mercaptopurine with it
Slide 96-

Refractory UC Oral tacrolimus (has been used in combination with oral aminosalicylates, AZA, or 6-MP) Vedolizumab Surgery
Slide 97-

Treatment Approaches for Ulcerative Colitis Link: Figure covering Treatment Approaches for Ulcerative Colitis Link: Table on Levels of Evidence for Therapeutic Interventions in Inflammatory Bowel Disease
Slide 98-

Mild/Moderate CD (Slide 1 of 2) Treatment of ACTIVE disease First-line therapy: Oral aminosalicylate Alternative therapies: Budesonide 9mg daily up to 8 weeks Metronidazole 10 – 20mg/kg/day for up to 10 weeks Ciprofloxacin 500mg bid for 6 to 10 weeks Rifaximin 800mg bid for 12 weeks Ciprofloxacin 500mg bid + metronidazole 250mg tid for 10 weeks
Slide 99-

Mild/Moderate CD (Slide 2 of 2) Specific choice of agent(s) for active disease can be informed by location of disease Ileocolonic or colonic Sulfasalazine OR oral mesalamine OR metronidazole +/- ciprofloxacin Perianal Sulfasalazine or oral mesalamine and/or metronidazole Small bowel Oral mesalamine or metronidazole Budesonide 9mg/day for terminal ileal or ascending colonic disease
Slide 100-

Moderate/Severe CD Treatment of ACTIVE disease First-line: Aminosalicylate OR metronidazole +/- ciprofloxacin PLUS prednisone at a dose of 40-60mg/day until resolution of symptoms or resumption of weight gain (7-28 days) If steroid refractory and/or fistulizing disease Add infliximab, adalimumab, or certolizumab +/- azathioprine, mercaptopurine, or methotrexate If no response to TNF-inhibitor and/or immunomodulator, change to natalizumab or vedolizumab
Slide 101-

Severe/Fulminant CD Treatment of ACTIVE disease May need surgical intervention (mass, obstruction, abscess, etc.) Administer IV hydrocortisone 100mg every 6 to 8 hours If no response to hydrocortisone in 5 to 7 days, then IV cyclosporine 4mg/kg/day OR infliximab is not attempted before
Slide 102-

Remission/Maintenance Therapy for Crohn’s Disease No role for long-term corticosteroid use First Line: Azathioprine or 6-mercaptopurine plus or minus oral aminosalicylate If intolerant to AZA or 6-MP, then try methotrexate Second Line: TNF-inhibitor plus or minus azathioprine or 6-mercaptopurine or methotrexate (if intolerant of AZA or 6-MP) Alternative: Vedolizumab
Slide 103-

Refractory CD Oral tacrolimus (has been used in combination with oral aminosalicylates, AZA, or 6-MP) Natalizumab Surgery
Slide 104-

Treatment Approaches for Crohn’s Disease Link: Figure covering Treatment Approaches for Crohn’s Disease Link: Table on Levels of Evidence for Therapeutic Interventions in Inflammatory Bowel Disease
Slide 105-

References (Slide 1 of 3) Hemstreet BA. Chapter 21. Inflammatory Bowel Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014. Hemstreet BA. Chapter 34. Inflammatory Bowel Disease. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 10e. New York, NY: McGraw-Hill; 2017. Wallace JL, Sharkey KA. Pharmacotherapy of Inflammatory Bowel Disease. In: Brunton LL, Chabner BA, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e New York, NY: McGraw-Hill; 2011. Friedman S, Blumberg RS. Inflammatory Bowel Disease. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 19e. New York, NY; McGraw-Hill; 2014.
Slide 106-

References (Slide 2 of 3) Lichtenstein GR, Hanauer SB, Sandborn WJ, et al. Management of Crohn’s disease in adults. Am J Gastroenterol 2009; 104(2): 465-483. Kornbluth A, Sachar DB, et al. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010; 105: 501-523. Triantafillidis JK, Merikas E, Georgeopoulos. Current and emerging drugs for the treatment of inflammatory bowel disease. Drug Design, Development, and Therapy 2011; 5: 185-210.
Slide 107-

References (Slide 3 of 3) Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor, MI. Accessed February 20, 2017. Lexicomp Online®, Lexi-Drugs®, Hudson, Ohio: Lexi-Comp, Inc. Accessed February 20, 2017.