1. “Tough Cases” Doug Wolf and Gil Y. Melmed Advances in IBD Hollywood, FL December, 2013

3. 71 yr retired virologist Diagnosed Crohn’s Disease at age 24 –Initial presentation in 1966 –Diarrhea and perianal abscess –Over next 30 years, 5 ileal resections and many I & D procedures for perianal abscesses 1966-1996 – multiple courses prednisone On prednisone since 1966 – addisonian- 1996 – 6-MP, metronidazole Not effective. Now what?

4. In 1997, age 55-Diverting ileostomy due to refractory fistulizing CD 5/2000 -Colonoscopy – Perianal fistulas, 40 cm of ileal Crohn’s disease, no colonic disease. 1/01 - started infliximab 5 mg/kg 0, 2, 6 and q8w 5/01 - Fistula healed after 5 th infliximab dose 6/01 - Ileostomy reversed 71 yr retired virologist

5. 8/13/01 – brought to the emergency room by ambulance –Hypotensive, hands cool, confused –Hypoxemic, tachycardic –CXR – widened mediastinum –ECHO – large pericardial effusion 71 yr retired virologist

6. What is the cause? –Heart failure from infliximab –Pneumonia from infliximab –Neoplasm from infliximab –Tuberculosis

8. Timing of TB with Infliximab – typically occurs between 3-5 th dose

9. Diagnosis: M. tuberculosis Treatment: –Rifampin, INH x 6 months –PZA, ethambutol x 2 months IFX held during TB therapy Symptoms (diarrhea, fistula) recur 71 yr retired virologist

10. Now What? Can he safely receive an anti-TNF agent ever again?

11. Decision made to resume IFX after 8m –Any concern for immunogenicity? –Reinduction? 71 yr retired virologist

12. Infliximab resumed: 0,2,6 re-induction. (low dose steroid coverage) –Initial response but gradual loss of response –Dose escalation –symptom recurrence –No TB recurrence! 71 yr retired virologist

13. Which treatment would you try next? –Start 6-MP –Adalimumab (ADA) (off-label) –ADA/6-MP combination –ADA/methotrexate combination Now What?

14. Continues low dose prednisone (5mg/d) Treated with ADA 160/80 induction and 40 mg q.o.w./6-MP. –Developed rash. –6-MP discontinued –ADA level checked – 3……. Switched to ADA/MTX –Excellent response 71 yr retired virologist

15. 2006 – Goes to Italy for 2 weeks Returns home with 3 days of feeling ill –Fever, SOB, weak –CXR and CT- left upper lobe consolidation 71 yr retired virologist

16. Differential diagnosis? a) Recurrent tuberculosis b) Pulmonary malignancy c) Methotrexate toxicity d) Legionella pneumophila e) Bacterial pneumonia 71 yr retired virologist

17. Bronchoscopy – negative Urinary Legionella antigen positive. 71 yr retired virologist

18. Adalimumab and methotrexate held Treated for Legionella pneumophia……. Levofloxacin 750 mg a day for 21 days Adalimumab and methotrexate resumed 1 week after completing Levofloxacin 71 yr retired virologist

19. 2y later- new painful, vesicular rash on left flank Medications: –Adalimumab –methotrexate 15 mg/wk –prednisone 9 mg/day What is this rash? 71 yr retired virologist

20. What to do about IBD medications? –Valtrex for Shingles –Hold adalimumab and methotrexate? How long? 71 yr retired virologist

21. Case 2

22. 32 y Lawyer 5y ago: diarrhea, pain/blood with defecation –CRS: “proctitis”, “elephant skin tags” “fissure”, “see GI” PMHx: ‘Back surgery’ Meds: Norco (back pain) FHx: No IBD or CRC Exam: Mild LLQ tenderness WBC 11.0, Hgb 11.9, alb 3.5, ESR 14, CRP 1.26

23. 32 y Lawyer T Ileum Tr Colon R Colon L Colon

24. Initiate treatment, or does he need further dx tests? –Serology? –Any need for imaging? –EGD? Capsule Endoscopy?

25. 32 y Lawyer Serology – –pANCA=45 (<15) –ASCA IgA = 17.5 (<20) –ASCA IgG = undetectable –OMPC 18.1 (<16.5) –CBir = 42 –“UC Predicted” CT Enterography –“thickening of wall of L colon” –“thickening of multiple mid small bowel loops with enhancement” Rheumatologist –“spondyloarthritis”

26. What treatment to start with?

27. 32 y Lawyer Treated with –2 weeks metronidazole –Pentasa 8/day and Rowasa enemas –adalimumab monotherapy At 6 weeks, no change in symptoms At 8 weeks, FS showed no change in mucosal inflammation

28. Now what??

29. 32 y Lawyer Adalimumab discontinued at 12 weeks due to ‘primary nonresponse’ Started Prednisone 40mg, 6-MP 1.5mg/kg Immediate improvement 4 months later, unable to wean below 15mg prednisone despite therapeutic 6MP levels

30. Now what???

31. 32 y Lawyer Patience with 6mp! –2 months later, still steroid-dependent Added infliximab Transient response after first 2 doses –Increased to 10mg q6w –Poor response

32. 32 y Lawyer Admitted for severe disease Colonoscopy –Deep ulcers, path with very active CMV –Polyp at 60cm (inflamed area), “tubular adenoma” –Referred for surgery –Dramatic clinical improvement with CMV treatment, refusing surgery –Infliximab drug levels low at 4w

33. 32 y Lawyer Discharged on ganciclovir slow taper Refused infliximab Went on carbohydrate-restricted diet off all meds 6m later in clinical and endoscopic remission 6m later (June, 2013) started to have symptoms again…

34. Now what???

35. 32y Lawyer Started prednisone and off-label ustekinumab July 2013 Weaned off prednisone Sept 2013 Continues to do well on 90mg q8w sq ustekinumab…