Inflammatory Bowel Disease: Why Should I Take My

Medications?

Sunanda V. Kane, MD, MSPH

Associate Professor of Medicine

Mayo Clinic College of Medicine

Rochester, Minnesota

Indeterminate colitis10%–15%

The Spectrum of IBD

CROHN’S DISEASE– Patchy inflammation– Mouth to anus

involvement– Full-thickness

inflammation– Variable involvement– Fistulas– Strictures – Extraintestinal

manifestations

ULCERATIVE COLITIS– Continuous

inflammation– Colon only– Superficial

inflammation– Variable involvement– Risk of cancer– Strictures (cancer)– Extraintestinal

manifestations

1–2 Million Americans

Potential Causes of IBD

GeneticPredisposition

ImmuneSystem

Abnormalities

Environmental Factors

Environmental Triggers

IBD

Antibiotics

Diet

Smoking

Infections

NSAIDs

Stress

NSAIDs=nonsteroidal anti-inflammatory drugs.

Diagnosing IBD

• Clinical history

• Physical examination

• Laboratory tests

• Endoscopy (gastroscopy/colonoscopy)

• Findings on X-ray films

• Tissue biopsy (pathology)

Questions Frequently MissedDuring History-Taking

• Family history for second-degree relatives

• NSAID use

• Antibiotic use

• Recent/previous infections

Clues in the Physical Examination

• Clues are present from head to toe– Aphthous oral ulcers

– Pale conjunctiva, red eyes

– Skin rashes

– Abdominal mass

– Perianal abnormalities

Ulcerative Colitis

Left-sided colitisProctitis Pancolitis

• The small intestine is not involved

Symptoms of Ulcerative Colitis

• Symptoms depend on extent and severity of inflammation– Rectal bleeding and urgency to evacuate

– Diarrhea

– Abdominal cramping

– Extraintestinal (systemic) symptomsJoint pain/swellingEye inflammationSkin lesions

Common Symptoms of Crohn’s Disease

• Diarrhea

• Abdominal pain and tenderness

• Loss of appetite and weight loss

• Fever

• Fatigue

• Rectal bleeding and anal ulcers

• Stunted growth in children

Laboratory Tests

• Routine laboratory tests are ordered first– Complete blood count to rule out infection and

anemia– C-reactive protein to assess for active inflammation– Chemistry panel for electrolytes and proteins– Thyroid-stimulating hormone for weight loss– Celiac testing of the physician’s choice

• Stool studies– Ova and parasite examinations, but yield may be low– Clostridium difficile toxin– White blood cell count, lactoferrin, and calprotectin

• A long stricture in the terminal ileum (Kantor’s string sign)

Diagnostic Studies:Small Bowel Series

Endoscopy

Ulcerative colitis Crohn’s disease

Endoscopy

Management Goals for IBD

Relievesymptoms

Treat inflammation

Treatcomplications

Address psychosocial

issues

Identify dysplasiaand detect

cancerImprove daily

functioning

Replenish nutritional

deficits

Minimize treatment toxicity

Maintain remission

EstablishDiagnosisEstablishDiagnosis

Medical Therapies for IBD

• 5-aminosalicylic acid (5-ASA) agents– Mesalamine

Delayed release tablets, Lialda®

Delayed release tablets, Asacol®

Controlled-release capsules, Pentasa®

Rectal suspension (Rowasa® enema)Rectal suppository (Canasa®)

– Sulfasalazine (Azulfidine®)

– Balsalazide (Colazal®)

– Olsalazine (Dipentum®)

Medical Therapies for IBD

• Antibiotics– Ciprofloxacin (Cipro®)– Metronidazole (Flagyl®)

• Steroids– Adrenocorticotropic hormone– Budesonide– Methylprednisolone (Medrol®)– Prednisone– Hydrocortisone (Cortenema®, Cortifoam®)

Medical Therapies for IBD

• Immunologic agents– Azathioprine (Imuran®, Azasan®)

– 6-Mercaptopurine (Purinethol®)

– Cyclosporine (Neoral®)

– Methotrexate

• Biologic agents– Infliximab (Remicade®)

– Adalimumab (Humira®)

– Natalizumab (Tysabri®)

Drugs don’t work in patients who don’t take them.

― C. Everett Koop, MD Former US Surgeon General

Factors that Affect Adherence

• Adherence is taking medications over a long period of time

• Extent, duration, and severity of disease affect adherence

• People who are more likely to adhere to therapy

– Have more disease flare-ups

– Are more knowledgeable about their treatment

• Clear instructions and educational materials provided by healthcare professionals increases knowledge about

– Importance of treatment

– Risks of non-adherence

Hall A, et al. Gastrointestinal Nurs. 2006;4:31-40.Lopez-Sanroman A, Bermejo F. Aliment Pharmacol Ther. 2006;24(Suppl 3):45-49.Kane SV. Aliment Pharmacol Ther. 2006;23:577-585.

Risk Factors for Non-Adherence

Risk Factor Odds Ratio (95% CI)

Married 0.46 (0.39-0.57)

Recent procedure 0.96 (0.93-0.99)

Greater extent of disease 0.55 (0.22-1.3)

Male gender 2.1 (1.2-4.8)

Taking more than 4 medications 2.5 (1.4-5.7)

Kane SV, et al. Am J Gastroenterol. 2001;96:2929-2932.

National Quality Forum Report

• Goals– Improve medication adherence by creating standards to

change the way healthcare professionals interact with patients

– Develop standard performance measures that could be implemented in patient care settings to improve adherence

• Recommendations– Adherence needs to be evaluated as a vital sign, every time

a patient is seen by a physician or nurse

– Ask the questions: Are you taking the medication, how are you taking it, and what is the dose?

Traynor K. Am J Health-Syst Pharm. 2005;62:2440-2442.

Significant Factors Associated with Risk of Not Refilling 5-ASA at

3 Months

3,574 UC patients with 5-ASA prescriptions; 1,530 (42.8%) patients did not refill at 3 months.* 12 months prior to index date.

Kane S, et al. Gastroenterology. 2007;132(4 Suppl 2):M1033.

Rectal 5-ASA*Glucocorticoid use*

Copay (per $1 increase)Lower daily pill load (per 1 pill decrease)Male genderMail orderPsychiatric history*

Patients More Likely to be Adherent

Patients Less Likely to be Adherent

Adherence Decreases Risk of Relapse

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From Kane S, et al. Am J Med. 2003;114:39-43; with permission.

Adherent

Non-adherent

Adherence Decreases Risk of Relapse

Kane S, et al. Am J Med. 2003;114:39-43.

• Prospective study in patients with UC in remission and taking mesalamine found chance of remission was – 89% in adherent patients– 39% in non-adherent patients

Non-Adherence is Associated with Recurrence

Follow-up

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Recurrence

From Kane S, et al. Am J Med. 2003;114:39-43; with permission.

Non-Adherence is Associated with Recurrence

Kane S, et al. Am J Med. 2003;114:39-43.

• 82% of patients with recurrence had not taken their medication

• 34% of patients remaining in remission had not taken their medication

Other Factors that Affect Adherence

• Adverse reactions to medications

• Need for many medications

• Effectiveness of treatment

• Convenience of treatment

Hall A, et al. Gastrointestinal Nurs. 2006;4:31-40.Lopez-Sanroman A, Bermejo F. Aliment Pharmacol Ther. 2006; 24(Suppl 3):45-49.Kane SV. Aliment Pharmacol Ther. 2006;23:577-585.

To Increase Treatment Adherence

• Simplify the treatment regimen

• Continue taking the medications

• Find support for emotional and social issues

Hall A, et al. Gastrointestinal Nurs. 2006;4:31-40.Lopez-Sanroman A, Bermejo F. Aliment Pharmacol Ther. 2006;24(Suppl 3):45-49.Kane SV. Aliment Pharmacol Ther. 2006;23:577-585.

Patient-Centered Self-Management Training

Robinson A, et al. Lancet. 2001;358:976-981.

Self-Guided Group

Control Group P-Value

Time to treat relapses 14.8 h 49.6 h <0.0001

Outpatient visits 0.9 2.9 <0.0001

Time spent visiting a doctor 1 h 6.2 h <0.0001

• Patients preferred guided self-management over traditional outpatient care

• Patient-centered self-management resulted in– Earlier treatment of relapses– Fewer hospital and primary care visits– Less time spent during a visit with a doctor

Why Take Your Medications?

• Possible decreased risk of colorectal cancer

• Decreased risk of disease progression

• Increased chance of disease regression

Velayos FS, et al. Am J Gastroenterol. 2005;100:1345-1353. Pica R, et al. Inflamm Bowel Dis. 2004;10:731-736. Picco MF, et al. Inflamm Bowel Dis. 2006;12:537-542.