2. 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

3. Indeterminate colitis 10%–15% The Spectrum of IBD CROHNS 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

4. Potential Causes of IBD Genetic Predisposition Immune System Abnormalities Environmental Factors

5. Environmental Triggers IBD Antibiotics Diet Smoking Infections NSAIDs Stress NSAIDs=nonsteroidal anti-inflammatory drugs.

6. Diagnosing IBD Clinical history Physical examination Laboratory tests Endoscopy (gastroscopy/colonoscopy) Findings on X-ray films Tissue biopsy (pathology)

7. Questions Frequently Missed During History-Taking Family history for second-degree relatives NSAID use Antibiotic use Recent/previous infections

8. 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

9. Ulcerative Colitis Left-sided colitisProctitisPancolitis The small intestine is not involved

10. Symptoms of Ulcerative Colitis Symptoms depend on extent and severity of inflammation –Rectal bleeding and urgency to evacuate –Diarrhea –Abdominal cramping –Extraintestinal (systemic) symptoms Joint pain/swelling Eye inflammation Skin lesions

11. Common Symptoms of Crohns Disease Diarrhea Abdominal pain and tenderness Loss of appetite and weight loss Fever Fatigue Rectal bleeding and anal ulcers Stunted growth in children

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

13. A long stricture in the terminal ileum (Kantors string sign) Diagnostic Studies: Small Bowel Series

14. Endoscopy Ulcerative colitis Crohns disease

15. Endoscopy

16. Management Goals for IBD Relieve symptoms Treat inflammation Treat complications Address psychosocial issues Identify dysplasia and detect cancer Improve daily functioning Replenish nutritional deficits Minimize treatment toxicity Maintain remission Establish Diagnosis

17. 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 ® )

18. Medical Therapies for IBD Antibiotics –Ciprofloxacin (Cipro ® ) –Metronidazole (Flagyl ® ) Steroids –Adrenocorticotropic hormone –Budesonide –Methylprednisolone (Medrol ® ) –Prednisone –Hydrocortisone (Cortenema ®, Cortifoam ® )

19. Medical Therapies for IBD Immunologic agents –Azathioprine (Imuran ®, Azasan ® ) –6-Mercaptopurine (Purinethol ® ) –Cyclosporine (Neoral ® ) –Methotrexate Biologic agents –Infliximab (Remicade ® ) –Adalimumab (Humira ® ) –Natalizumab (Tysabri ® )

20. Drugs dont work in patients who dont take them. C. Everett Koop, MD Former US Surgeon General

21. 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.

22. Risk Factors for Non-Adherence Risk FactorOdds Ratio (95% CI) Married 0.46 (0.39-0.57) Recent procedure 0.96 (0.93-0.99) Greater extent of disease0.55 (0.22-1.3) Male gender2.1 (1.2-4.8) Taking more than 4 medications2.5 (1.4-5.7) Kane SV, et al. Am J Gastroenterol. 2001;96:2929-2932.

23. 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.

24. 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 gender Mail order Psychiatric history* Patients More Likely to be Adherent Patients Less Likely to be Adherent

25. Adherence Decreases Risk of Relapse 0 25 50 75 100 Patients Remaining in Remission, % 403632Adherent n = Non-adherent n =593228 01224Time (months)36 From Kane S, et al. Am J Med. 2003;114:39-43; with permission. Adherent Non-adherent

26. 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

27. Non-Adherence is Associated with Recurrence Follow-up Medication Refilled in Previous 6 Months, % No Recurrence Recurrence From Kane S, et al. Am J Med. 2003;114:39-43; with permission.

28. 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

29. 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.

30. 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.

31. Patient-Centered Self-Management Training Robinson A, et al. Lancet. 2001;358:976-981. Self-Guided Group Control GroupP-Value Time to treat relapses14.8 h49.6 h<0.0001 Outpatient visits0.92.9<0.0001 Time spent visiting a doctor1 h6.2 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

32. 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.