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Do I really have a chance of winning a debate when my side is to continue meds when CA develops?

Pro: An IBD patient on a biologic and/or an immunomodulator, who develops a malignancy: skin cancer solid tumor lymphoma may continue or restart these medications, if needed to treat IBD.

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Do I really have a chance of winning a debate when my side is to continue meds when CA develops?

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  1. Pro: An IBD patient on a biologic and/or an immunomodulator, who develops a malignancy:skin cancersolid tumorlymphomamay continue or restart these medications, if needed to treat IBD Miguel Regueiro, MD, FACG, AGAFProfessor of MedicineClinical Head, IBD CenterUniversity of Pittsburgh Medical Ctr

  2. Do I really have a chance of winning a debate when my side is to continue meds when CA develops?

  3. Thank you for slides • Jim Lewis • Jean Fred Colombel • Corey Siegel (also for photos of Tom!)

  4. Important questions in pts who develops cancer on IBD meds: Did the medicine cause the cancer? What is the risk of: - continuing the med in terms of worsening cancer or - discontinuing the med in terms of worsening IBD?

  5. Let’s consider three types of cancer: Skin Cancer Lymphoma Solid Tumors

  6. Case • 50 year old male • 30 year history of small bowel Crohn’s • 1 prior bowel resection • Current meds – 6MP + Adalimumab • 3 BM per day • Colonoscopy – few scattered aphthous ulcers (i1) in the neo-TI

  7. Case (cont) • 2 years prior diagnosed with Non Melanoma Skin Cancer (Basal Cell Ca) • 2 weeks ago newly diagnosed with Squamous Cell Cancer

  8. Is skin cancer caused by or are patients at increased risk from… azathioprine/6MP Methotrexate antiTNFs

  9. Thiopurines and Skin Cancer NMSC MELANOMA Long M. Gastroenterology 2012:143:390-9. Singh H Gastroenterology 2011:141:1612-20 Peyrin-Biroulet L. Gastroenterology 2011:141:1621-8 Peyrin-Biroulet L. Am J Gastroenterol 2012 doi: 10.1038/ajg.2012.181

  10. Timing of Thiopurines and NMSC (esp. older ages) CESAME SIR and 95% CI Peyrin-Biroulet L. Gastroenterology 2011:141:1621-8

  11. Anti-TNF and Skin Cancer (IBD data) NMSC MELANOMA NR Long M. Gastroenterology 2012:143:390-9. Singh H Gastroenterology 2011:141:1612-20 Peyrin-Biroulet L. Gastroenterology 2011:141:1621-8 Peyrin-Biroulet L. Am J Gastroenterol 2012 doi: 10.1038/ajg.2012.181

  12. Clinical Questions • Is skin cancer risk increased by therapy? • Thiopurines – yes • Methotrexate – don’t know, probably not • Biologics – no NMSC, maybe melanoma • If so, does the risk of continuing therapy outweigh the benefits? • In this case – consider stopping thiopurine • Uncertain if risk will decline • Annual skin exam and regular use of sunscreen and hats

  13. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  14. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  15. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  16. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  17. Skin: Stop or Continue? What I do-Consult with Dermatology and then.….

  18. Lymphoma

  19. Questions • Does immunosuppressant therapy increase the risk of lymphoma? • Do the benefits outweigh the risks? • What do you do when a lymphoma develops in the setting of IBD meds?

  20. AZA/6-MP are probably related to Lymphoma (Meta-analysis): SIR 4.06 SIR = 4.06, 95% CI 2.01 – 7.28 Kandiel A et al. Gut. 2005:54:1121-25

  21. CESAME – 6MP/AZA OnlyLymphoma: HR 5.3 Beaugerie L. Lancet 2009 DOI:10.1016/S0140-6736(09)61302-7

  22. Risk of NH Lymphoma with anti-TNF + IM treatment for Crohn’s Disease: A Meta-Analysis • 8905 patients representing 20,602 pt-years of exposure • 13 Non-Hodgkin’s lymphomas  • Mean age 52, 62% male • 10/13 exposed to IM* (really a study of combo Rx) 6.1 per 10,000 pt-years Siegel et al, CGH 2009;7:874. *not reported in 2

  23. CESAME – Combo 6MP/AZA and antiTNF: SIR = 10.2 Beaugerie L. Lancet 2009 DOI:10.1016/S0140-6736(09)61302-7

  24. Clinical Questions • Does immunosuppressant therapy increase the risk of lymphoma? • Thiopurines – yes, but risk may revert after discontinuation • antiTNFs – Probably not • Combination – Yes and probably more than monotherapy

  25. Risk:Benefit Ratio

  26. Hepatosplenic T Cell Lymphoma • 41 cases from FDA AERS among patients with IBD1 • Thiopurine alone 17 • Anti-TNF alone 1 • Combination therapy 23 • Characteristics2 • Median age 22.5 (12 – 58) • 93% male • Median time since initiation of thiopurines ~6 years • Deepak P. Am J Gastroenterol 2013; 108:99–105 • Kotlyar D. Clin Gastroenterol Hepatol 2011;9:36–41

  27. Lymphoma - Number Needed to Harm ‡ Kandiel A et al. Gut. 2005:54:1121-25 * 5 year survival = 68% for NHL, 85% for HD, estimated at 75% for this example ‡ Kandiel A et al. Gut. 2005:54:1121-25 * 5 year survival = 68% for NHL, 85% for HD, estimated at 75% for this example

  28. What to do if lymphoma develops while taking IMM/antiTNF?

  29. Case – Stop or Continue? • 39 yo male CD in remission on 6MP/IFX for 8 yrs. • Now with weight loss, sweats, and low grade fevers

  30. Crohn’s ds case: NHL while taking 6MP/IFX.

  31. After consulting with the oncologist…. …we stopped the 6MP/antiTNF, but after 3 months of chemorx, the antiTNF was resumed. We did not restart the 6MP.

  32. On CT: Hepatosplenic T cell lymphoma – enlarged spleen, otherwise nonspecific. Thiopurine must be stopped!

  33. Solid Tumors

  34. Case Continue or Stop? • 58 yo female with severe UC who has been on IFX/6MP (50mg/d) for past 1yr • Just diagnosed with intraductal breast CA (T1N0MX) • Strong FHx breast CA, pt opts for bilateral mastectomy • After consultation with oncology, the decision is to cont meds

  35. No clear association between thiopurines/antiTNFs and solid tumors in IBD

  36. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  37. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  38. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  39. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  40. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  41. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  42. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  43. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  44. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  45. Lymphoma: Stop or Continue? 3 types, Consult with Oncology and then.….

  46. Solid Tumor: Stop or Continue? Consult with Oncology and then.….

  47. Solid Tumor: Stop or Continue? Consult with Oncology and then.….

  48. Solid Tumor: Stop or Continue? Consult with Oncology and then.….

  49. Should we continue or stop IBD meds if a cancer develops? Depends on IBD

  50. Deep Remission If in deep remission, maybe stopping IBD meds is ok and not restarting them

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