Managing IBS/IBD - Winter 2024 PDF

MANAGEMENT OF IBS/IBD José P. Rodríguez Pérez, PharmD, BCPS Clinical Assistant Professor Nova Southeastern University Barry and Judy Silverman College of Pharmacy Integrated Disease Management 1 – Winter 2024 [email protected] OBJECTIVES Identify differing characteristics of Inflammatory Bowel Disease...

MANAGEMENT OF IBS/IBD José P. Rodríguez Pérez, PharmD, BCPS Clinical Assistant Professor Nova Southeastern University Barry and Judy Silverman College of Pharmacy Integrated Disease Management 1 – Winter 2024 [email protected] OBJECTIVES Identify differing characteristics of Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS) Describe major pathophysiologic findings and clinical symptoms of IBS/IBD Gather subjective and objective information about a patient with IBS/IBD in order to understand the relevant medical and medication history and clinical status of the patient Assess information collected and analyze the clinical effects of the patient’s therapy to identify and prioritize problems Provide or modify non-pharmacologic and pharmacologic recommendations in order to provide individualized patient-centered care options and their modalities for use in IBS/IBD DEFINITIONS Ulcerative Colitis Crohn’s Disease Inflammatory condition (mucosal) that only affect colon and rectum Inflammatory condition (transmural) that can affect any part of the gastrointestinal system (mouth to anus) GI SYSTEM EPIDEMIOLOGY Ulcerative Colitis Incidence: 1.2 – 20 cases per 100,000 persons per year Prevalence: 7.6 – 246 cases per 100,000 persons per year Crohn’s Disease Incidence: 6 – 15.5 cases per 100,000 persons per year Prevalence: 3.6 – 214 cases per 100,000 persons per year Both sexes are affected equally with IBD 20 – 30% more women are affected with CD 60% males are affected with UC ETIOLOGY INFECTIOUS ENVIRONMENTAL GENETIC IMMUNE SYSTEM 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 GENETIC FACTORS 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 IMMUNE SYSTEM The immune system plays a critical role in the pathogenesis of IBD and include both autoimmune and non-autoimmune phenomena Inflammatory response may indicate an abnormal regulation of the normal immune response or an autoimmune reaction to self-antigens In IBD, the bowel mucosa is infiltrated with lymphocytes, plasma cells, macrophages and neutrophils Many extraintestinal manifestations have an immunologic component ENVIRONMENTAL FACTORS Psychological Factors Mental health changes appear to correlate to disease flares in IBD Dietary Factors Diet composition may influence the makeup of the gut microbiota Intake of refined sugars → development of CD Increased protein intake → higher risk of developing IBD Smoking Factors Smoking appears to be protective in UC and is associated with fewer disease flare-ups and reduced disease severity In CD, smoking is associated with increased disease frequency and severity PATHOPHYSIOLOGY DIFFERENCES Extent and distribution of the inflammation Depth of involvement (intestinal wall) CLINIC AL PRESENTATION DEPTH OF BOWEL WALL INVOLVEMENT EXTRAINTESTINAL MANIFESTATIONS Extraintestinal Manifestations Hepatobiliary Joints Ocular Dermatologic and mucocutaneous Hematologic, pulmonary, and metabolic Complications Non-alcoholic fatty liver (50% of patients), autoimmune hepatitis, liver abscess, cirrhosis, gallstones (34% of CD patients) Peripheral and axial involvement; arthritis (5 – 20% of patients); axial involvement → more progressive → reumathologist Dry eyes, iritis, uveitis, and conjunctivitis (up to 29%); may be parallel to the severity of the intestinal disease Erythema nodosum, aphthous ulceration (4 – 20% of CD patients → may be parallel to the severity of the intestinal disease), sweet’s syndrome, and pyoderma gangrenosum Anemia (74% prevalence), thromboembolism (VTE), osteopenia (32-36%) or osteoporosis (2 – 15%), bronchiectasis ULCERATIVE COLITIS (UC) ULCERATIVE COLITIS (UC) UC is confined to the rectum and colon Lesions affect the mucosal and submucosal layers Mucosal appearance includes edema, erosions, and lesions are continuous Disease distribution Proctitis: 30 – 60% Rectal inflammation Distal (Left-sided colitis): 16 – 45% Inflammation confined to the descending colon Extensive colitis: 14 – 35% Inflammation from transverse to descending colon CLINICAL PRESENTATION Signs and Symptoms Abdominal cramping Frequent bowel movements (bloody) Weight loss Fever and tachycardia in severe disease Inflamed nodules Physical Examination Hemorrhoids, anal fissures, perirectal abscess, erythema Laboratory tests ↓ Hbg/Hct ↑ ESR, CRP, and fecal calprotectin (non-specific neutrophilic marker of inflammation) Leukocytosis and hypoalbuminemia with severe disease + perinuclear antineutrophil cytoplasmic antibodies NORMAL LAB VALUES Erythrocyte sedimentation rate (ESR) Hemoglobin (Hgb) Hemotocrit (Hct) M: 13.5 – 18 g/dL F: 12 – 16 g/dL M: 38 – 50% F: 36 – 46% WBC CRP Fecal calprotectin 4 – 11 x 10^3/µL 0 – 0.05 mg/dL < 50 mcg/g M: < 20 mm/hr F: < 30 mm/hr SEVERITY CLASSIFIC ATION OF ULCERATIVE COLITIS ACUTE SEVERE UC (ASUC) Severe patients that require hospitalization > 6 bloody stools per day HR > 90 bpm At least one of the following: T > 37.8 Hbg < 10.5 g/dL ESR > 30 mm/hr DISEASE ACTIVITY DISEASE ACTIVITY PATHOLOGY SEVERITY (UCEIS) VISUAL COMPARISON HIGHER RISK FOR COLECTOMY Extensive colitis Age < 40 y/o Steroid dependence Deep ulcers History of hospitalization High ESR/CRP C.difficile or cytomegalovirus infection COMPLICATIONS - UC Hemorrhoids Anal fissures Perirectal abscesses Colorectal carcinoma (CRC) Massive colonic hemorrhage Toxic Megacolon TREATMENT DEFINITIONS Induction of remission Therapy to target acute disease flare Maintenance of remission Therapy to minimize further acute flares Refractory treatment Failed response to standard therapy GOALS OF THERAPY IN IBD Provide symptom relief Inducing remission Improve quality of life Maintain adequate nutritional status Relieve intestinal inflammation Decrease frequency of recurrence Resolve complications Nutritional support Malabsorption or maldigestion (Due to inflammatory process) Avoid specific foods that may exacerbate their symptoms Patients may benefit from enteral nutrition NONPHARMACOLOGIC TREATMENT Parenteral nutrition may be an option but is reserved for patients with severe malnutrition or failure to enteral therapy Probiotics Reestablishment of normal bacteria flora in the gut nonpathogenic Escherichia coli Nissle, bifidobacteria, lactobacilli, Streptococcus thermophilus, Saccharomyces boulardii Reduction in bacterial adhesion and competition for nutrients with pathogenic bacteria Production of antibacterial substances Surgery NONPHARMACOLOGIC TREATMENT May involve resection of segments of intestine that are affected, drainage of abscesses or correction of complications such as: Fistulas, strictures, obstructions, perforations, etc. PHARMACOLOGIC TREATMENT Treatment is based on Type UC vs 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 PHARMACOLOGIC TREATMENT Proctitis Inflammation confined to the rectum Topical agents (suppository) Distal disease (left-sided disease) Inflammation limited to areas distal to the splenic flexure Systemic or topical therapy or in combination Extensive colitis Inflammation extending proximal to the splenic flexure Systemic agents Pancolitis Inflammation occurring in most of the colon Systemic therapy May add topical therapy if needed/appropriate MILD-MODERATE DISTAL UC Treatment of active disease First line: Topical aminosalicylates (enema/suppository) Mesalamine If inadequate or no response, use an oral aminosalicylate or topical corticosteroid Sulfasalazine or Mesalamine May combine oral and topical aminosalicylates MILD-MODERATE DISTAL UC Mesalamine suppository or enema used 3 times per week Remission/Maintenance Therapy Oral aminosalicylate tapered to a maintenance dose Topical or oral corticosteroids have no role in maintenance therapy Sulfasalazine or Mesalamine MILD-MODERATE EXTENSIVE UC First-line Treatment of active disease Alternative Oral aminosalicylate Budesonide (Uceris) 9 mg/d Sulfasalazine or Mesalamine MILD-MODERATE EXTENSIVE UC Reduce oral aminosalicylate to maintenance dose Remission/Maintenance Therapy If budesonide is used for induction, then continue for up to 8 weeks MODERATE-SEVERE UC Budesonide 9 mg/day First-line therapy Prednisone 40-60 mg/d Treatment of active disease If no response Add azathioprine, mercaptopurine, infliximab, adalimumab, or golimumab MODERATE-SEVERE UC Taper prednisone Remission/Maintenance Therapy Continue azathioprine, mercaptopurine, infliximab, adalimumab, or golimumab if previously added Then after 1-2 months, reduce oral aminosalicylate dose to maintenance dose SEVERE-FULMINANT UC Methylprednisolone 40 – 60 mg daily 3 – 5 day course of IV corticosteroids Hydrocortisone 100 mg IV every 6-8 hours Treatment of active disease Patients refractory to IV corticosteroids (no response in 3 – 5 days) IV cyclosporine or infliximab SEVERE-FULMINANT UC If remission achieved with IV hydrocortisone Change to oral prednisone and add azathioprine, mercaptopurine, infliximab, certolizumab, adalimumab, vedolizumab or tofacitinib Attempt to withdraw prednisone after 1-2 months Remission/Maintenance Therapy If corticosteroid refractory disease and needed cyclosporine to achieve remission Change IV cyclosporine to oral cyclosporine and add either azathioprine or mercaptopurine or vedolizumab or continue infliximab May consider TNF-inhibitor at maintenance dose in the future, but if using oral cyclosporine, must use azathioprine or mercaptopurine with it REFRACTORY UC Oral tacrolimus (has been used in combination with oral aminosalicylates, azathioprine, or mercaptopurine) Vedolizumab Surgery UC TREATMENT APPROACH PRACTICE All the following are complications of Ulcerative Colitis EXCEPT: a. Colon Cancer b. Fistulas c. Hemorrhoids d. Toxic Megacolon PRACTICE Which medication is most effective for treatment of mild-moderate proctitis in a patient with UC? a. Sulfasalazine oral b. Mesalamine suppository c. Hydrocortisone enema d. Ciprofloxacin oral CROHN’S DISEASE (CD) CROHN’S DISEASE (CD) Characterized as a transmural inflammatory process May occur at any part of the GI tract Cobblestone appearance due to deep mucosal ulceration combined with nodular submucosal thickening Disease distribution Terminal ileum (most common) Often have areas of normal bowel separating segments of diseased bowel resulting in discontinuous disease CLINICAL PRESENTATION Signs and symptoms: Physical examination Laboratory tests Malaise and fever Abdominal mass and tenderness ↑WBC, ESR, CRP, fecal calprotectin Perianal fissure or fistula (+) anti–Saccharomyces cerevisiae antibodies Abdominal pain Frequent bowel movement Hematochezia (rectal bleeding) Weight loss and malnutrition COBBLESTONE APPEREANCE CLASSIFICATION OF DISEASE Crohn’s Disease Activity Index (CDAI) Used most often to gauge response to therapy and determine remission and is employed mostly in the research setting Score system ranges from 0 – 600 Score > 150 → active disease Harvey – Bradshaw Index (HBI) Scoring system that is also used for CD A decreased of 3 points is defined as clinical response < 4 → complete remission CDAI HARVEYBRADSHAW INDEX SEVERITY CLASSIFICATION OF CD Mild – moderate CD Typically ambulatory, no evidence of dehydration, systemic toxicity, < 10% loss of body weight or abdominal tenderness, mass or obstruction CDAI: 150 – 220 Moderate – severe CD Failed mild-moderate treatment response Have fever, weight loss, abdominal pain or tenderness, vomiting, intestinal obstruction or significant anemia CDAI: 221 - 450 Severe – fulminant CD Presence of persistent symptoms or evidence of systemic toxicity despite corticosteroid or biologic treatment, presence of cachexia, rebound tenderness, intestinal obstruction, abcess CDAI: > 450 COMPLICATIONS - CD Strictures Fistulas Nutritional deficiencies Folic acid,Vitamin B12,Vitamins A and D, calcium, magnesium, iron, zinc Decreased food intake, intestinal loss, malabsorption, hypermetabolic state, drug nutrient interactions, and long term parenteral nutrition Bleeding (less than UC) Colorectal carcinoma (less than UC) TREATMENT GOALS Suppression of the immune system Induce and maintain remission Severity of disease and locations → treatment approach Improve nutritional status Surgery Most effective and safe option; take insurance into consideration MILD-MODERATE CD Extensive Sulfasalazine Perianal Small bowel Infliximab +/metronidazole Budesonide 9 mg/d for terminal ileal or ascending colonic disease Specific choice of agent for active disease can be informed by location of disease MODERATE-SEVERE CD First-line Treatment of active disease Prednisone 40-60mg/d until resolution of symptoms or resumption of weight gain (7-28 days) Add infliximab, adalimumab, or certolizumab +/- azathioprine, mercaptopurine, or methotrexate If steroid refractory and/or fistulizing disease If no response to TNF-inhibitor and/or immunomodulator, change to natalizumab, vedolizumab or ustekinumab SEVERE-FULMINANT CD May need surgical intervention (mass, obstruction, abscess, etc.) Treatment of active disease Administer IV methylprednisolone or hydrocortisone If no response to steroids, then TNF-inhibitors REMISSION-MAINTENANCE THERAPY FOR CD No role for long-term corticosteroid use Sulfasalazine if disease is confined to the colon TNF-inhibitor +/azathioprine or mercaptopurine or methotrexate (if intolerant to azathioprine or mercaptopurine) Alternative: Vedolizumab, natalizumab, risankizumab and ustekinumab CD TREATMENT APPROACH PRACTICE Which of the following drugs should not be used as maintenance therapy in a patient with Crohn’s disease? a. Prednisone b. Methotrexate c. Certolizumab d. Azathioprine IRRITABLE BOWEL SYNDROME (IBS) DEFINITION Is a GI syndrome that is the most commonly diagnosed GI condition, and is characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause IBS with constipation (IBS-C) IBS with diarrhea (IBS-D) EPIDEMIOLOGY Prevalence is 10% worldwide among adults More predominant in younger patients and women PATHOPHYSIOLOGY Results from altered somatovisceral and motor dysfunction of the intestine from a variety of causes Abnormal CNS processing of afferent signals may lead to visceral hypersensitivity, with the specific nerve pathway affected determining the exact symptomatology expressed. This visceral hypersensitivity is a neuroenteric phenomenon that is independent of motility and psychological disturbances. Factors known to contribute to these alterations include genetics, motility factors, inflammation, colonic infections, mechanical irritation to local nerves, stress, and other psychological factors Two types of 5-HT receptors exist within the gut: serotonin type 3 (HT3) and serotonin type 4 (HT4), which are responsible for secretion, sensitization, and motility. There is an increase in the postprandial levels of 5-HT in the GI tract in those diagnosed with diarrhea-predominant IBS compared to those who are not CLINICAL PRESENTATION Signs and symptoms Non-GI symptoms Other concurrent conditions Lower abdominal pain Abdominal bloating and distention Diarrhea symptoms, > 3 stools per day Extreme urgency Passage of mucus Constipation symptoms, < 3 stools per week, straining, incomplete evacuation Psychological symptoms Depression and anxiety Urinary symptoms Fatigue Dyspareunia Fibromyalgia Functional dyspepsia Chronic fatigue syndrome DIAGNOSIS (ROME IV CRITERIA) Recurrent abdominal pain or discomfort at least 1 day per week in the last 3 months associated with two or more of the following: Relieved with defecation Onset associated with a change in frequency of stool Onset associated with a change in form (appearance) of stool Symptom onset at least 6 months before diagnosis NON-PHARMACOLOGIC TREATMENT Increase excersice Increase diatary fiber and water intake Reduce caffeine, alcohol, and artificial sweeteners intake Reduce the intake of fermentable oligosaccharides, disaccharides, monossacharides, polyps (FODMAPs) Decrease stress, anxiety, depression Cognitive behavioral therapy, stress management, relaxation therapy and hypnotherapy PHARMACOLOGIC TREATMENT (IBS -C) PEG laxatives → osmotic laxatives Mild symptoms, may not improve abdominal pain Intestinal secretagogues → increases intestinal fluid and GI transit Linaclotide Plecanatide Lubiprostone Tenapanor Sodium/hydrogen exchanger 3 (NHE3) inhibitor Increases intestinal fluid secretion and motility Tegaserod (short term for IBS-C in women) 5-HT4 partial agonist Increases gastric secretions and promotes motility Caution: Increases ischemic events PHARMACOLOGIC TREATMENT (IBS -D) Loperamide Decreases intestinal transit, enhances water and electrolyte absorption and strengthens rectal sphincter tone Alosetron (IBS-D in women) 5-HT3 antagonist Severe symptoms Caution: Ischemic colitis Rifaximin Rifamycin antibiotic Improves abdominal pain, stool consistency and bloating Eluxadoline (C-IV) Mu-opioid receptor agonist Improves abdominal pain and stool consistency PAIN IN IBS Antispasmodic agents may be used for abdominal pain Dicyclomine (Bentyl) Hyoscyamine (Levsin) Anticholinergic side effects Tricyclic Antidepressants Amitriptyline, nortriptyline, imipramine Some benefit in treatment of IBS-D associated with moderate-severe pain Modulating perception of visceral pain, altering GI transit time and treating underlying comorbidities IBS TREATMENT APPROACH PRACTICE Which of the following medications can be used to the treatment of IBS-D? a. Linaclotide b. Rifaximin c. Tegaserod d. Plecanatide REFERENCES Hemstreet BA. Inflammatory Bowel Disease. In: DiPiro JT,Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw Hill; 2023. https://accesspharmacy-mhmedicalcom.ezproxylocal.library.nova.edu/content.aspx?bookid=3097&sectionid=265901908 Fabel PH, Shealy KM. Diarrhea, Constipation, and Irritable Bowel Syndrome. In: DiPiro JT,Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw Hill; 2023. Accessed March 21, 2024. https://accesspharmacymhmedical-com.ezproxylocal.library.nova.edu/content.aspx?bookid=3097&sectionid=267924854 Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG clinical guideline: Ulcerative colitis in adults. American Journal of Gastroenterology. 2019;114(3):384-413. doi:10.14309/ajg.0000000000000152 Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: Management of crohn’s disease in adults. American Journal of Gastroenterology. 2018;113(4):481-517. doi:10.1038/ajg.2018.27 Stone C-B. Inflammatory bowel disease (IBD). AGA GI Patient Center. February 12, 2024. https://patient.gastro.org/inflammatory-bowel-diseaseibd/ Inflammatory bowel disease (IBD). Johns Hopkins Medicine. May 16, 2022. https://www.hopkinsmedicine.org/health/conditions-anddiseases/inflammatory-bowel-disease. OpenStax LL&. Anatomy and physiology II. Overview of the Digestive System | Anatomy and Physiology II. https://courses.lumenlearning.com/suny-ap2/chapter/overview-of-the-digestive-system/. MANAGEMENT OF IBS/IBD José P. Rodríguez Pérez, PharmD, BCPS [email protected]