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What adverse reactions to immunomodulators and biologics: 1) mandate discontinuation of therapy and 2) when can medications be continued? Miguel Regueiro, M.D. Professor of Medicine Associate Chief, Education Clinical Head and Co-Director, IBD Ctr University of Pittsburgh Medical Ctr 1 Very little to no evidenced based data on this subject, so… I called some friends for help. 2 Corey Siegel – after 1 minute of laughter, “I was asked to give this talk and turned it down…good luck!” 3 David Rubin – “What are you kidding me?!?!” 4 Asher Kornbluth – “I’m sorry, I can’t hear you.” Ed Loftus – Clearly has gone over his own cliff……. Jean Fred Colombel – yelled something in French about the color blue being sacred, the rest I couldn’t understand. 7 So, with no help from my “friends” 8 I will give you my opinion on what to do with IMMs/antiTNFs when an AE occurs. We need to individualize this decision based on severity of IBD and AE. I look forward to further discussion and opinion in the panel session. 9 What are the main side-effects of 6MP/Azathioprine? Event Frequency Estimate Stop therapy due to AE 11% Allergic reactions 2% Nausea 2% Hepatitis 2% Pancreatitis 3% Serious infections 5% non-Hodgkin’s lymphoma Siegel CA, et al. APT 2005 (weighted average); Siegel CA, et al. CGH 2009; Beaugerie L, et al. Lancet 2009. 0.04%-0.09% (4-9/10,000) Adverse Events Associated with anti-TNF Treatment Event Estimated Frequency Stop therapy due to adverse event 10% Infusion or injection site reactions 3%-20% Drug related lupus-like reaction 1% Serious infections 3% Skin ? 1-20% Tuberculosis 0.05% (5/10,000) Non-Hodgkin’s lymphoma (combo) 0.06% (6/10,000) Multiple sclerosis, heart failure, serious liver injury Case reports only Siegel CA.. The inflammatory bowel disease yearbook, volume 6. 2009; Infliximab package insert; Vermeire, Gastro 2003; Cush, Ann Rheum Dis 2005; Lenercept study group, Neurology 1999; ATTACH trial 2003 Continue or Stop Rxent? Focus on three adverse event categories – cases from my clinic • • • • Infections Malignancy Skin Complications Thank you Drs Siegel, Rubin, Loftus, Kornbluth, and Colombel for your slides 12 Infections - Continue or Stop? • 33 yo CD IFX/AZA recently relocated from Louisville to Pittsburgh. • For the past month he had cough, myalgias, weight loss, and low grade fevers. • PPD/Quantiferon negative, but CXR shows…….. 13 CXR – Reticulonodular infiltrate 14 Bronchoscopy – what is the dx? 15 Histoplasmosis • Urine antigen also positive for Histoplasmosis • Stop AZA/IFX and rx ketoconazole • Would you restart IFX/AZA after infxn clears? 16 Increased Risk of Opportunistic Infections (Mayo) – AZA/antiTNF Medication Odds Ratio (95% CI) P value Any Medication (5-ASA, AZA/6-MP, steroids, MTX, infliximab) 3.5 (2 - 6.1) <0.0001* 5-ASA 1.0 (0.6 - 1.6) 0.94 Corticosteroids 3.4 (1.8 - 6.2) <0.0001* 6-MP/azathioprine 3.1 (1.7 - 5.5) 0.0001* Methotrexate 4.0 (0.4 - 44.1) 0.26 Infliximab 4.4 (1.2 - 17.1) 0.03 Toruner M et al, Gastroenterology 2008; 134:929-36. Older Age Is Associated with Opportunistic Infections • Age at IBD diagnosis: –Odds Ratio (per 5 years), 1.1 (1.1-1.2) • Age at first Mayo visit: 0 – 23 –24 – 36 –37 – 49 – ≥ 50 – 1.0 (reference) 1.2 (0.5 – 2.8) 1.1 (0.5 – 2.5) 3.0 (1.2 – 7.2) Toruner M et al, Gastroenterology 2008; 134:929-36. The type of infections more prevelant with anti-TNFs (granulomatous) • Bacterial •Tuberculosis •Atypical mycobacterial infection •Listeriosis • Invasive Fungal •Histoplasmosis •Coccidioidomycosis •Candidiasis •Aspergillosis •Pneumocystosis Lee JH et al. Arthritis Rheum. 2002;46:2565-70 Velayos FS et al. Inflamm Bowel Dis. 2004;10:657-60 Bergstrom L et al. Arthritis Rheum. 2004;50:1959-66 20 Case - Stop or Continue? • 27 yo male with a h/o severe Crohn’s ds who is in remission for 4 years on 6MP 1 mg/kg. • Over the past year he has had recurrent “bumps” over his hands and arms. • Not painful, but aesthetically displeasing and affecting social life 23 What is the diagnosis? 24 Warts (likely papillomavirus) • Despite treatment he continues to have problems with warts. • The 6MP is lowered but it is not until 6MP is stopped that his warts resolve. • Can 6MP be started again in the future? 25 Thiopurines Increase the Incidence of Certain Viral Infections - Warts Prospective study (n=230) NS * 20 18 NS 16 2.0 * 1.5 Patients (%) Infection/patient-year 14 1.0 12 10 8 6 4 0.5 2 0 AZA+ n=169 AZA– n=61 Upper respiratory tract infections AZA+ n=169 AZA– n=61 Herpes virus flare-ups 0 AZA+ AZA– Warts at the entry in the study AZA+ Appearance of increased number of warts Seksik P et al. Aliment Pharmacol Ther 2009;29:1106-13. NS = not significant AZA– Case - Continue or Stop? • 58 yo in remission on IFX monotx for 5yrs (first 1.5 yrs on 6MP as well). • Due for IFX infusion in 3 weeks. • 1 wk ago developed severe pain along back, “thought kidney stone” • 4 days ago developed “blisters” along back (very painful) 27 Diagnosis? Give IFX in 3 weeks? 28 Does Zoster mandate stopping? • If pt due for antiTNF and active zoster, I wait for blisters to “dry/scab” • In this case she received IFX on schedule as her lesions resolved • Side Note: Shingles vaccine is live and contraindicated in immunosuppressed patients 29 Case - Continue or Stop? • 41 yo UC in remission on Adalimumab 40mg qow and 6MP 50mg/d for 3 yrs • 2 weeks ago worsening diarrhea – no bleeding, but “feels like flare” • Colonoscopy shows…….. 30 What is your dx and would you change the ADA/6MP? 31 Clostridium difficile Infection and IBD Increasing percentage of C. diff infections are IBD patients Increasing number of hospitalizations in IBD patients with C. diff •Classic risk factors disappearing •Pseudomembranes usually not present •Low threshold for checking in IBD patients with flares •Should you stop immunosuppression? Conflicting data Issa M, et al. Clin Gastroenterol Hepatol 2007; 5: 345-51. Infections: Stop or Continue? What I do….Consult with ID..then.. VIRAL EBV, HSV, CMV, HIV, HepB, HepC, HPV BACTERIAL Strep/Staph Mycobact FUNGAL Histoplasm Coccidio Other C Diff Thiopurine antiTNF 34 Infections: Stop or Continue? What I do…. VIRAL EBV, HSV, CMV, HIV, HepB, HepC, HPV Thiopurine BACTERIAL Strep/Staph Mycobact FUNGAL Histoplasm Coccidio Other C Diff Stop if severe: Individualize as to who to restart 6MP/AZA antiTNF 35 Infections: Stop or Continue? What I do…. VIRAL EBV, HSV, CMV, HIV, HepB, HepC, HPV Thiopurine BACTERIAL Strep/Staph Mycobact FUNGAL Histoplasm Coccidio Other C Diff Stop May need to stop + Rx virus Individualize as to who to restart 6MP/AZA antiTNF Continue Prob ok to continue, except active Hep B 36 Infections: Stop or Continue? VIRAL EBV, HSV, CMV, HIV, HepB, HepC, HPV BACTERIAL Strep/Staph Mycobact Thiopurine Stop Stop + Rx May need to stop then + Rx virus individualize (if typical bact, Individualize as eg strep, often to who to restart can rx through) 6MP/AZA antiTNF Continue Prob ok to continue, except active Hep B FUNGAL Histoplasm Coccidio Other C Diff Stop + Rx then individualize (if typical bact, eg strep, often can rx through) 37 Infections: Stop or Continue? What I do…. VIRAL EBV, HSV, CMV, HIV, HepB, HepC, HPV Thiopurine BACTERIAL Strep/Staph Mycobact Stop Stop + Rx May need to stop then + Rx virus individualize FUNGAL Histoplasm Coccidio Other C Diff Stop + Rx then Restart when cleared Individualize as to who to restart 6MP/AZA antiTNF Continue Prob ok to continue, except active Hep B Stop + Rx then individualize Stop + Rx then Restart when cleared 38 Infections: Stop or Continue? What I do…. VIRAL EBV, HSV, CMV, HIV, HepB, HepC, HPV Thiopurine BACTERIAL Strep/Staph Mycobact Stop Stop + Rx May need to stop then + Rx virus individualize FUNGAL Histoplasm Coccidio Other C Diff Stop + Rx then Restart when cleared Probably continue Stop + Rx then Restart when cleared Probably continue Individualize as to who to restart 6MP/AZA antiTNF Continue Prob ok to continue, except active Hep B Stop + Rx then individualize 39 Malignancy -Lymphoma - Solid Tumors 40 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 41 Large periaortic LNs involving left renal cortex – diagnosis? 42 Non-Hodgkin’s Lymphoma • • • • What do you do now? Stop IFX and continue 6MP? Stop 6MP and continue IFX? Stop both? 43 In contrast: Hepatosplenic T cell lymphoma – enlarged spleen, otherwise nonspecific 44 AZA/6-MP are probably related to Lymphoma (Meta-analysis): SIR 4.06 Author Observed Expected Connell 0 0.52 Kinlen 2 0.24 Farrell 2 0.05 Lewis 1 0.64 Fraser 3 0.65 Korelitz 3 0.61 Total 11 2.71 SIR = 4.06, 95% CI 2.01 – 7.28 Kandiel A et al. Gut. 2005:54:1121-25 CESAME – 6MP/AZA Only Lymphoma: HR 5.3 At cohort entry N # HR (95% CI) Lymphomas 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 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 6.1 per 10,000 pt-years Mean age 52, 62% male 10/13 exposed to IM* (really a study of combo Rx) 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 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 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 49 No clear association between thiopurines/antiTNFs and solid tumors in IBD Study Types of cancer Number of patients Statistically significant lung, breast 1955 NO Fraser 2002 breast, bronchial, renal 6262 NO Connell 1994 gastric, lung, breast, cervical 755 NO Armstrong 2010 …..but DO seem associated with increased risk of skin cancers and lymphoma Malignancy: Stop or Continue? What I do Consult with Oncology and then.…. LYMPHOMA HSTC Lymphoma SOLID TUMORS Thiopurine antiTNF 51 Malignancy: Stop or Continue? What I do Consult with Oncology and then.…. LYMPHOMA Thiopurine Continue or start: Previously Rx’d and inactive >1 yr antiTNF Continue or start: Previously Rx’d and inactive >1 yr HSTC Lymphoma SOLID TUMORS 52 Malignancy: Stop or Continue? What I do Consult with Oncology and then.…. LYMPHOMA Thiopurine HSTC Lymphoma SOLID TUMORS Continue or start: Previously Rx’d and inactive >1 yr Stop: New Lymphoma, esp EBV on 6MP antiTNF Continue or start: Previously Rx’d and inactive >1 yr Stop: New Lymphoma ?Restart 53 Malignancy: Stop or Continue? What I do Consult with Oncology and then.…. Thiopurine LYMPHOMA HSTC Lymphoma Continue or start: Previously Rx’d and inactive >1 yr Must Stop: Stop: New Lymphoma, esp EBV on 6MP antiTNF SOLID TUMORS -Has been a fatal lymphoma. -Even if eradicated, avoid future 6MP Continue or start: Previously Rx’d and inactive >1 yr Stop: New Lymphoma, esp EBV on 6MP 54 Malignancy: Stop or Continue? What I do Consult with Oncology and then.…. Thiopurine antiTNF LYMPHOMA HSTC Lymphoma Continue or start: Previously Rx’d and inactive >1 yr Must Stop: SOLID TUMORS -Has been a fatal lymphoma. Stop: New Lymphoma, esp EBV on 6MP -Even if eradicated, avoid future 6MP Continue or start: Previously Rx’d and inactive >1 yr Must Stop: -Has been a fatal lymphoma. Stop: New Lymphoma, esp EBV on 6MP -Even if eradicated, avoid future antiTNF? 55 Malignancy: Stop or Continue? What I do Consult with Oncology and then.…. Thiopurine antiTNF LYMPHOMA HSTC Lymphoma SOLID TUMORS Continue or start: Previously Rx’d and inactive >1 yr Must Stop: Continue or start: -Has been a fatal lymphoma. -Previously Rx’d Stop: New Lymphoma, esp EBV on 6MP -Even if eradicated, avoid future 6MP Continue or start: Previously Rx’d and inactive >1 yr Must Stop: -Has been a fatal lymphoma. Stop: New Lymphoma, esp EBV on 6MP -Even if eradicated, avoid future antiTNF? -even active (nonEBV) solid tumors ok to continue 56 Malignancy: Stop or Continue? What I do Consult with Oncology and then.…. Thiopurine antiTNF LYMPHOMA HSTC Lymphoma SOLID TUMORS Continue or start: Previously Rx’d and inactive >1 yr Must Stop: Continue or start: -Has been a fatal lymphoma. -Previously Rx’d Stop: New Lymphoma, esp EBV on 6MP -Even if eradicated, avoid future 6MP Continue or start: Previously Rx’d and inactive >1 yr Must Stop: -Has been a fatal lymphoma. Stop: New Lymphoma, esp EBV on 6MP -Even if eradicated, avoid future antiTNF? -even active (nonEBV) solid tumors ok to continue Start: Previously Rx’d 57 Malignancy: Stop or Continue? What I do Consult with Oncology and then.…. Thiopurine antiTNF LYMPHOMA HSTC Lymphoma SOLID TUMORS Continue or start: Previously Rx’d and inactive >1 yr Must Stop: Continue or start: -Has been a fatal lymphoma. -Previously Rx’d Stop: New Lymphoma, esp EBV on 6MP -Even if eradicated, avoid future 6MP Continue or start: Previously Rx’d and inactive >1 yr Must Stop: -Has been a fatal lymphoma. Stop: New Lymphoma, esp EBV on 6MP -Even if eradicated, avoid future antiTNF? -even active (nonEBV) solid tumors ok to continue Start: Previously Rx’d Stop: Active cancer (but unless mets, ok to restart once rx’d?) 58 I think skin AEs are increasing and becoming most problematic Related to the IBD Skin manifestations of IBD Secondary to medical therapy Consequence of nutritional deficiencies Skin AEs secondary to Meds - Malignancy - Immune mediated -Thank you, Jean Fred for your slides 60 Do GI’s know Skin? 61 Basal Cell Cancer Plantar Psoriasis Nodular Pigmented BCC Squamous Cell Ca 62 Take home message: Get Dermatology involved! 63 What’s the dx? Stop or Cont ADA? • 67 yo m CD remission 3 yrs ADA – has 15 of these lesions removed over past 2 years 64 Stop or Continue – Basal Cell CA • 67 yo m CD remission 3 yrs ADA – 15 basal cells removed over past 2 years • He opts to continue ADA given good CD response. • He follows closely with derm – for smaller lesions topical 5FU has been effective. 65 What is this? What do you do? • 59 yo f CD sun exposure entire life – deep remission on 6MP for 15 years • Last 2 yrs has had Moh’s surgery x 2 to remove these lesions from face – 3 from neck 66 Stop or Continue – Squamous Cell cancer • The 6MP is stopped and in the next 2 years she has had 1 more SCC but her CD remains in remission 67 High Rates of BCC and SCC in IBD pts exposed to thiopurines – active or previous exposure Yearly incidence rate (per 1,000 patient-years) 32 incident NMSC: 20 BCC and 12 SCC 6 >65 years Thiopurine therapy 5.70 Continuing 5 Discontinued 50-65 years 3 2.59 <50 years 2 1.96 1 0.84 0.66 0.60 0.38 0 Cases of NMSC (n) Patient-years 4.04 Never received 4 0 9 3 0 13590 7924 15736 6 3 3 3 3 2 2319 1530 4968 743 526 2383 Peyrin-Biroulet. Gastroenterology 2011 Anti-TNFs also associated with Basal Cell and Squamous Cell Cancers • Prospective observational registries and studies • Patients with RA, PsA or ankylosing Spondylitis receiving TNFi therapy Patients treated with TNFi have a significantly increased risk of developing an NMSC (1.45, 95% CI 1.15 to 1.76). Mariette X. Ann Rheum Dis. 2011 Melanoma and anti-TNF therapy in IBD • Retrospective cohort (and nested casecontrol) study • LifeLink claims database 108,518 IBD pts • Crohn’s (but not UC) associated with increased risk of melanoma (IRR 1.45, OR 1.88 (95% CI 1.08-3.29) 95% CI 1.13-1.85) • Biologics increased risk of melanoma Long M, et al. Gastroenterology 2012. Epub ahead of print. What is your dx? How do you rx? • 27 yo female CD on ADA in remission for 3 yrs but over past 6 mos develops progressive skin lesions over ears and scalp (with hair loss) 74 Anti-TNF psoriaform lesions – in my opinion the most common and difficult antiTNF AE to manage • She sees dermatology who tries topical treatment (steroids, dapsone) without benefit. • They recommend adding MTX but she wants to have children soon • She stops the ADA. Her skin improves and 1 yr later she is pregnant but is beginning to have CD sx’s. 75 What about this case? Fungal? Other? • 25 yo male UC on IFX in remission but over past 6 mos has patchy skin lesions under the arms and gluteal cleft 76 “Inverse Psoriasis” from antiTNF • His skin improves with topical steroids/dapsone but not completely • After adding MTX 10mg per week the lesions resolve. 77 Psoriasis associated with Anti-TNF therapy • Described with all the anti-TNF: class effect • Described in patients receiving treatment for diverse indications (RA, IBD, psoriasis, psoriatic arthritis, ankylosing spondylitis) • Often leads to therapy discontinuation • First IBD case reported in 2004 in a CD patient treated with infliximab 150 Increasingly recognised side-effect of anti-TNF therapy in the IBD literature 18 November 2008 (1) (2) August 2011 Verea MM. Ann Pharmacther 2004; (1) G. Fiorino. APT 2009; (2) Cullen G. In press 2011 Psoriasis associated with Anti-TNF therapy FDA WARNING Psoriasis associated with Anti-TNF therapy What is the magnitude of the problem in IBD patients? Psoriasis associated with Anti-TNF therapy in IBD: a new series and review of 120 cases from the Literature Case reports (50) + current series(30) + GETAID Series (62) 150 cases for analysis Psoriasis details Location: •Palmoplantar - 42% •Scalp - 42% •Trunk – 31% •Flexures – 31% •Facial – 16% Cullen G. APT 2011 When you see this – think antiTNF mediated Psoriasis • Several phenotypes: • Palmoplantar pustular psoriasis: form most commonly associated with anti-TNF therapy (even in patients treated for plaque psoriasis) JF Rahier.CGH 2010; Courtesy of Franck Delesalle ….or this……antiTNF Psoriasis • Several phenotypes: • Inverse psoriasis (type of psoriasis in plaques) In Psoriasis – Manson publishing; Courtesy of Franck Delesalle Skin: Stop or Continue? What I doConsult with Dermatology and then.…. NMSC – Basal Cell Squamous Cell Melanoma PSORIASIAS-like (Immune mediated) Thiopurine antiTNF 87 Skin: Stop or Continue? What I doConsult with Dermatology and then.…. NMSC – Basal Cell Squamous Cell Melanoma PSORIASIAS-like (Immune mediated) Thiopurine Continue or start: Active or Past, as long as Dermatology monitoring Stop: Only if significant recurrence or potential for disfiguring sequelae antiTNF 88 Skin: Stop or Continue? What I doConsult with Dermatology and then.…. NMSC – Basal Cell Squamous Cell Melanoma PSORIASIAS-like (Immune mediated) Thiopurine Continue or start: Active or Past, as long as Dermatology monitoring Stop: Only if significant recurrence or potential for disfiguring sequelae antiTNF Continue or start: Active or Past, as long as Dermatology monitoring Stop: Rarely necessary 89 Skin: Stop or Continue? What I doConsult with Dermatology and then.…. NMSC – Basal Cell Squamous Cell Thiopurine Continue or start: Active or Past, as long as Dermatology monitoring Stop: Only if significant recurrence or potential for disfiguring sequelae antiTNF Melanoma PSORIASIAS-like (Immune mediated) Continue/start: -eradicated -melanoma free for > 1 yr -no mets Stop: New Onset? Continue or start: Active or Past, as long as Dermatology monitoring Stop: Rarely necessary 90 Skin: Stop or Continue? What I doConsult with Dermatology and then.…. NMSC – Basal Cell Squamous Cell Thiopurine Continue or start: Active or Past, as long as Dermatology monitoring Stop: Only if significant recurrence or potential for disfiguring sequelae antiTNF Continue or start: Active or Past, as long as Dermatology monitoring Stop: Rarely necessary Melanoma PSORIASIAS-like (Immune mediated) Continue/start: -eradicated -melanoma free for > 1 yr -no mets Stop: New Onset? Continue/start: -eradicated -melanoma free for > 1 yr -no mets Stop: New Onset 91 Skin: Stop or Continue? What I doConsult with Dermatology and then.…. NMSC – Basal Cell Squamous Cell Thiopurine Continue or start: Active or Past, as long as Dermatology monitoring Stop: Only if significant recurrence or potential for disfiguring sequelae antiTNF Continue or start: Active or Past, as long as Dermatology monitoring Stop: Rarely necessary Melanoma PSORIASIAS-like (Immune mediated) Continue/start: -eradicated -melanoma free for > 1 yr -no mets Continue or start: Stop: New Onset? -any psoriasis, past or present - MTX may be useful in rxing antiTNF-mediated skin ds Continue/start: -eradicated -melanoma free for > 1 yr -no mets Stop: New Onset 92 Skin: Stop or Continue? What I doConsult with Dermatology and then.…. NMSC – Basal Cell Squamous Cell Thiopurine Continue or start: Active or Past, as long as Dermatology monitoring Stop: Only if significant recurrence or potential for disfiguring sequelae antiTNF Continue or start: Active or Past, as long as Dermatology monitoring Stop: Rarely necessary Melanoma PSORIASIAS-like (Immune mediated) Continue/start: -eradicated -melanoma free for > 1 yr -no mets Continue or start: Stop: New Onset? Continue/start: -eradicated -melanoma free for > 1 yr -no mets Stop: New Onset -any psoriasis, past or present - MTX may be useful in rxing antiTNF-mediated skin ds Continue: Mild, <5% skin, responds to topical tx or MTX Stop: >5%, nonresponsive to psoriasis tx 93 Summary: Stop or Continue Rx? • IMMs and biologics are associated with rare, but potentially serious AEs • Most AEs do not mandate IMM/antiTNF cessation – individualize the decision • I would stop/hold IMM/antiTNF for: – – – – – Active opportunistic infections (rare) Lymphoma/Cancer (very rare) Recurrent skin cancers Non-responsive psoriasis to antiTNF Allergic/idiosyncratic drug rxns • Once AE resolves, usually restart meds 94 UPMC IBD Center: Physicians and Staff When you go out tonight, beware of: Bill Sandborn and Jean Fred Colombel 97