1 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 Miguel Regueiro, MD, FACG, AGAF Professor of Medicine Clinical Head, IBD Center University of Pittsburgh Medical Ctr
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1 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.
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Pro: An IBD patient on a biologic and/or an immunomodulator, who develops a
malignancy:skin cancersolid tumorlymphoma
may continue or restart these medications, if needed to treat IBD
Miguel Regueiro, MD, FACG, AGAFProfessor of MedicineClinical Head, IBD CenterUniversity of Pittsburgh Medical Ctr
Do I really have a chance of winning a debate when my side is to continue meds when CA develops?
Thank you for slides
• Jim Lewis
• Jean Fred Colombel
• Corey Siegel (also for photos of Tom!)
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Important questions in pts who develops cancer on IBD meds:
1. Did the medicine cause the cancer?
2. What is the risk of:
- continuing the med in terms of worsening cancer or
- discontinuing the med in terms of worsening IBD?
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Let’s consider three types of cancer:
-Skin Cancer
-Lymphoma
- Solid Tumors
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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
Case (cont)
• 2 years prior diagnosed with Non Melanoma Skin Cancer (Basal Cell Ca)
• 2 weeks ago newly diagnosed with Squamous Cell Cancer
Is skin cancer caused by or are patients at increased risk from…
-azathioprine/6MP
-Methotrexate
-antiTNFs
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Thiopurines and Skin Cancer
NMSC MELANOMA
Long M. Gastroenterology 2012:143:390-9. Singh H Gastroenterology 2011:141:1612-20Peyrin-Biroulet L. Gastroenterology 2011:141:1621-8Peyrin-Biroulet L. Am J Gastroenterol 2012 doi: 10.1038/ajg.2012.181
Timing of Thiopurines and NMSC (esp. older ages)
Peyrin-Biroulet L. Gastroenterology 2011:141:1621-8
CESAME
Anti-TNF and Skin Cancer (IBD data)
NMSC MELANOMA
Long M. Gastroenterology 2012:143:390-9. Singh H Gastroenterology 2011:141:1612-20Peyrin-Biroulet L. Gastroenterology 2011:141:1621-8Peyrin-Biroulet L. Am J Gastroenterol 2012 doi: 10.1038/ajg.2012.181
NR
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
Skin: Stop or Continue? What I do-Consult with Dermatology and then.….
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NMSC – Basal Cell Squamous Cell Melanoma
Thiopurine
antiTNF
Skin: Stop or Continue? What I do-Consult with Dermatology and then.….
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NMSC – Basal Cell Squamous Cell Melanoma
Thiopurine Continue or start:Active or Past, as long as Dermatology monitoringMTX prob ok
Stop:Only if significant recurrence or potential for disfiguring sequelae
antiTNF
Skin: Stop or Continue? What I do-Consult with Dermatology and then.….
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NMSC – Basal Cell Squamous Cell Melanoma
Thiopurine
antiTNF Continue or start:Active or Past, as long as Dermatology monitoring
Stop:NO, rarely necessary to stop
Skin: Stop or Continue? What I do-Consult with Dermatology and then.….
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NMSC – Basal Cell Squamous Cell
Melanoma
Thiopurine Start:-eradicated/resected/no mets-melanoma free for > 1 yrStop/Restart: -Hold for new onset?-Maybe ok to continue -Restart if melanoma free-Stop for metastatic ds
antiTNF
Skin: Stop or Continue? What I do-Consult with Dermatology and then.….
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NMSC – Basal Cell Squamous Cell
Melanoma
Thiopurine
antiTNF Start:-eradicated/resected/no mets-melanoma free for > 1 yrStop: -New Onset-?Restart if melanoma free > 1 yr-Do not restart <1yr or mets
Lymphoma
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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?
AZA/6-MP are probably related to Lymphoma (Meta-analysis): SIR 4.06
AuthorAuthor ObservedObserved ExpectedExpected
ConnellConnell 00 0.520.52
KinlenKinlen 22 0.240.24
FarrellFarrell 22 0.050.05
LewisLewis 11 0.640.64
FraserFraser 33 0.650.65
KorelitzKorelitz 33 0.610.61
TotalTotal 1111 2.712.71
SIR = 4.06, 95% CI 2.01 – 7.28Kandiel A et al. Gut. 2005:54:1121-25
CESAME – 6MP/AZA OnlyLymphoma: HR 5.3
At cohort entry
N # Lymphomas
HR (95% CI)
Never exposed to thiopurines
10,810 6 Reference
On therapy with thiopurines
5,867 16 5.3 (2.0 – 13.9)
Previously discontinued thiopurines
2,809 2 1.0 (0.2 – 5.1)
Beaugerie L. Lancet 2009 DOI:10.1016/S0140-6736(09)61302-7
• 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)
Risk of NH Lymphoma with anti-TNF + IM treatment for Crohn’s Disease: A Meta-Analysis
NHL rate per 10,000
SIR 95% CI
SEER all ages 1.9 - -
IM alone 3.6 - -
Anti-TNF + IM vs SEER 6.1 3.23 1.5-6.9
Anti-TNF+ IM vs IM alone 6.1 1.7 0.5-7.1
Siegel et al, CGH 2009;7:874. *not reported in 2
6.1 per 10,000 pt-years
CESAME – Combo 6MP/AZA and antiTNF: SIR = 10.2
Therapy Patients # Lymph SIR 95% CI
Never thiopurine or TNF
22,706 6 1.5 0.5 – 3.2
Current thiopurine without TNF
14,729 13 6.5 3.5 – 11.2
Current thiopurine + TNF
1,929 2 10.2 1.2 – 36.9
Beaugerie L. Lancet 2009 DOI:10.1016/S0140-6736(09)61302-7
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