Crohn s Disease. From research to bedside

Transcription

1 Crohn s Disease From research to bedside

2 Primary Care Of The Crohn s Disease Patient

3 Primary Physician s Concerns Vaccination Cancer Cervical Skin Osteoporosis

4 Problems Associated With Vaccinating The Crohn s Patient The vaccination rate Response of the patient to vaccines Appropriate vaccines for the Crohn s patient

5 Vaccination Rate IBD patients have more to gain from vaccination; but they are less likely to be vaccinated

6 The Vaccine Problem Immunomodulators and biologics used to treat IBD puts patients at risk for infections Several of these are vaccine preventable Multiple case reports of infections including fulminate hepatitis or fatal varicella IBD patients are not being vaccinated appropriately Keene JK, et al JAMA 1978;45-6 Domm S, et al Br.Jderm 2008;

7 The Vaccination Problem Survey of 169 IBD patients 145 on current/previous immunosuppression 28% reported regular flu shots 9% reported receiving pneumovax Common reasons for not getting vaccinated: Lack of awareness Fear of side effects Melmed, GV et al Am J Gastroenterol 2006, 101;

8 Why Not Let The Gastroenterologist Manage The Vaccinations? Are they knowledgeable? Are they interested? Keene JK, et al JAMA 1978;45-6

9 The Vaccination Problem Survey of 108 gastroenterologists (Fall 2009) Poor knowledge regarding the appropriate vaccines to recommend 20-30% would erroneously give live vaccine to immunosuppressed patients 25-35% would erroneously hold live vaccine to immunocompetent patients Wasan, SK et al Inflamm Bowel Dis, 2011 Dec; 17(12)

10 GI Physicians Do Not Inquire About Immunization History How Often N (%) Always 20 (18.5) Most of the time 36 (33.3) Half of the time 5 (4.7) Sometimes 40 (37) Never 7 (6.5) Wasan, SK et al Inflamm Bowel Dis, 2011 Dec; 17(12)

11 Gastroenterologists Put the Onus for Vaccinations on the PCP Majority thought PCP was responsible for: Determining which vaccinations to give (65%) Administering the vaccine (85%) Wasan, SK et al Inflamm Bowel Dis, 2011 Dec; 17(12)

12 PCPs Hesitant to Treat IBD Patients Survey of 61 attendees at a family medicine review course Only 37% if doctors felt comfortable providing primary care to IBD patients across a range of illness severity Only 30% felt comfortable coordinating vaccinations for the immunosuppressed IBD patient Selby L, et al Dig Dis Sci. 2011;54:

13 Will Vaccination Work?

14 Immune Response in IBD: Will the Vaccine Work? 64 IBD patients vaccinated with pneumococcal vaccine 45% of patients on combination anti-tnf and immunomodulator mounted a response 80% of non immunosuppressed IBD patients mounted a response 85% if healthy controls mounted a response Authors concluded that newly diagnosed IBD patients should undergo vaccination before the initiation of immunosuppressive therapy Melmed GY, et al, Amer J gastroenterol 2010; 105:

15 Immune Response in IBD: Will the Vaccine Work? 36 IBD patients on AZA/6MP vaccinated with influenza, pneumovax, and tetanus Responses to vaccine not significantly different compared to controls Authors concluded that therapy with 6MP or AZA does not interfere with patients ability to mount a normal immune response Donan I, et al Inflamm Bowel Dis, 2012 Feb; 18 (2) 261-8

16 Immune Response in IBD: Will the Vaccine Work? 96 pts. on 5ASAs, AZA, anti-tnf, or combination (AZA/anti-TNF) given pneumovax Response to vaccine not significantly different compared to 5ASA control in pts. on AZA/6MP (P=0.43) Response to vaccine decreased in pts. On infliximab or infliximab and AZA and controls (P<.05) Authors conclude therapy with 6MP/AZA does not interfere with the pts. ability to mount a normal immune response Fiorino G et al Infllam Beo dis, 2012 Jun 18(6)

17 Immune Response in IBD: Will the Vaccine Work? On monotherapy with immunomodulator? Normal immune response compared with controls or patients on 5ASAs On monotherapy with anti-tnf? Diminished immune response compared with controls or patients on 5ASAs Melmed P et al Clin Gastrenterol Hepato. 2007;5;851-6

18 Immune Response in IBD: Will the Vaccine Work? Study of H1N1 influenza vaccine in 105 IBD patients Immunosuppressed patients with lower rate of serprotection than non-immunosuppressed (44% vs 64%, P=.06) Combined immunosuppression with even lower titers compared to patients on monotherapy Cullen G. et al Gut 2012 Mar; 61(3);

19 Immune Response in IBD: Will the Vaccine Work? On combination of immunomodulator and an anti-tnf agent? Diminished immune response to vaccine compared to patients on monotherapy with immunomodulator or 5ASAs Mamula P. et al Clin Gastrointerol Hapatol. 2007;

20 Immune Response in IBD: Will the Vaccine Exacerbate IBD? Although limited data in IBD patients, there is data in patients with other chronic immunologic diseases (MS, SLE) that vaccinations do not exacerbate disease activity

21 Immune Response in IBD: Will the Vaccine Exacerbate IBD? H1N1 vaccine 575 patients on immunomodulators or anti-tnfs received vaccine between 11/09-3/10 in 14 European countries Well tolerated Four weeks after vaccination: absence of flare was observed is 96.7% of Crohn s disease patients Rashier, JF gut 2011; 60,

22 Vaccinating the IBD Patient

23 Standard Immunization Schedule Vaccine Tetanus, dipthera, pertussis Dosing Schedule Substitute 1 time dose of Tdap for Td booster; then boost with Td every 10 years. For pts. >65 yrs. Td booster every 10 years Human papilloma virus (HPV) Varicella Zoster 3 doses in pts. Between years 2 doses 1 dose for patients >60 years Measles, Mumps, Rubella (MMR) 1 or 2 doses for pts. Between yrs. 1 dose after 50 if other risk factors Influenza 1 dose annually Pneumoccal 1 or 2 doses for pts. Between yrs. 1 dose after 50 if other risk factors Hepatitis A Hepatitis B Keene JK, et al JAMA 1978; doses in patients with risk factors 3 doses in patients with risk factors

24 General Vaccination Considerations Titers to check at first office visit MMR If vaccination history of unknown Varicella- If vaccination history or history of chicken pox/zoster unknown Hepatitis A- except those with evidence of protective titer within 5 years of vaccine administration Hepatitis B- except those with evidence of protective titer within 5 years of vaccine administration cdc

25 General Vaccination Considerations Vaccinations to administer in specific patient groups regardless of immunosuppressive drug use TdapT HPV Influenza Pneumococcal Hepatitis A (if not immune) Hepatitis B (if not immune) Meningococcal Keene JK, et al JAMA 1978;45-6

26 General Vaccination Considerations Vaccinations to consider if NO plans to start immunosuppressive therapy in 4-12 weeks MMR (if not immune) Varicella (if not immune) Zoster (if older than 59) Wasik SK et al Am J Gastro (6)

27 Definition of Immunosuppressed Rx with glucocorticoid (prednisone>20 mg/d or equivalent for 2 or more weeks, and within 3 months of stopping Rx with effective doses of 6MP/AZA or recent discontinuation within previous 3 months Rx with methotrexate or recent discontinuation within previous 3 months Rx with anti-tnf agent or recent discontinuation within previous 3 month Significant protein-calorie malnutriton Sands, BE et al Inflamm Bowel Dis, 2004;10;

28 Summary IBD patients have poor immunization rates IBD patients can mount a response to vaccines Immunogenicity may be diminished in patients on combination therapy or immunomodulator and anti-tnf agent IBD disease will not be affected by vaccination When possible, vaccinate prior to initiation of immunosuppressive agents

29 Resources CDC:

30 Available CDC Poster Keene JK, et al JAMA 1978;45-6

31 Cancer

32 PAP Testing and Cervical Cancer

33 PAP Testing in IBD Patients Risk factors for abnormal PAP: multiple sexual partners, cigarette use, OCP use Higher prevalence of abnormal PAP smears in women with IBD Associated with immunomodulator use Vaccination for HPV is warranted Kane S et al Amer J Gastro 2008;103: Singh H et al Gastro 2009; 136:

34 PAP Testing in IBD Patients Document an up-to-date PAP smear when starting immunosuppressive therapy Rule out HPV infection Rule out an abnormal cervical cytology Women on immunomodulators should follow ACOG guidelines for yearly PAP testing Kane S et al Amer J Gastro 2008;103: Singh H et al Gastro 2009; 136:

35 Skin Cancer

36 Non Melanoma Skin Cancer (NMSC) Estimated 3.5 million cases per year of NMSC Increased risk in immunosuppressed IBD pts. 6MP/AZA use (OR: 4.27, CI ) Anti-TNF use (OR: 2.18, CI ) Combined 6MP/AZA and anti-tnf agent (OR: CI ) Educate pt. on sun protection strategies Yearly derm evaluation recommend in pts. on immunosuppressive agents Long MD et al Clin J Gastro Hepatol : Long Md et al Gastro 2012:143(2):

37 Bone Health In IBD Patients (Osteoporosis)

38 Bone Health In IBD Patients IBD patients have an increased risk of osteoporosis and osteopenia Risk factors: severity of intestinal inflammation, steroids, BMI, smoking, hypogonadism, vit D deficiency, older age, lifestyle, family hx, and previous fracture DEXA scan is gold standard osteopenia T score of -1 ti -2.5 osteoporosis T score <-2.5 Increased risk of fractures in pts. with low BMD Bernstein CN Clin Gastro Hepatol, 2006, 4: Lichtenstein GR et al Inflamm Bowel Dis. 2006,12(8):

39 What Is The Risk? Osteopenia: 18% to 42% increased risk Osteoporosis: 22% to 77% increased risk This data has a large spread which may be due to referral bias Population study of >6,000 patients calculated the relative risk at 1.4 (which is a 40% increased risk

40 For IBD: Who Gets a DEXA Scan? Post menopausal women and men >50 Patients on steroids for >3 months History of low trauma fracture Hypogonadism AGA Guidelines

41 Treatment For All Patients Lifestyle modification (no smoking, exercise, limit alcohol to 3 drinks/day) Supplement vitamin D and calcium Minimize steroids

42 What Is FRAX And How Can We Use It? Validated fracture risk score from WHO Can be used instead of DEXA scan in some patients Can be accessed from your computer or as an APP on your smart phone

43 Fracture Probability Is Age, BMD, and Gender Keene JK, et al JAMA 1978;45-6

44 Keene JK, et al JAMA 1978;45-6

45 Keene JK, et al JAMA 1978;45-6

46 Questions Keene JK, et al JAMA 1978;45-6