Il paziente: strategie di approccio nei vari ambiti d immunosoppressione, tradizionale e 2.0

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1 Il paziente: strategie di approccio nei vari ambiti d immunosoppressione, tradizionale e 2.0 Vito Di Marco Gastroenterology & Epatology Di.Bi.M.I.S. University of Palermo

2 Common clinical scenarios and drugs associated with reactivation of hepatitis B in patients with detectable HBsAg or Anti HBc Clinical scenarios 1. Cancer chemotherapy Solid cancer Hematologic cancer 2. Solid organ transplantation 3. Bone marrow or stem cell transplantation 4. Immunosuppressive therapy for benign conditions (e.g., rheumatoid arthritis, psoriasis, and inflammatory bowel disease) Drugs associated with HBV reactivation 1. Conventional chemotherapeutic drugs 2. New chemotherapeutic drugs 3. Immunosuppressive drugs 4. Targeted (e.g., anti CD20, anti TNF) therapy 5. Corticosteroids

3 Questions to Ask Your Doctor If You Are Taking Immunosuppressants What is my risk of carrying HBV? Should I be screened for HBV? If You Have a Past or Current HBV Infection Do I have any risk factors for HBV reactivation? What can I do to help prevent reactivation? Your doctor can measure your risk and decide whether to prescribe antiviral drugs to help prevent reactivation Your level of risk depends on several factors: the type of drug you are taking how long you have been taking the drug your type of HBV infection

4 Keys questions 1. Should patients who will undergo long term immunosuppressive drug therapy be screened for HBV before starting treatment? 2. Is antiviral prophylaxis needed for HBsAg Positive patients who will undergo immunosuppressive drug therapy? 3. Is antiviral prophylaxis needed for HBsAg Negative, Anti HBc Positive patients who will undergo immunosuppressive drug therapy?

5 Prophylaxis and therapy in immunocompromised patients Active carrier Inactive carrier Anti core Haematology Therapy Universal prophylaxis Universal prophylaxis* or Monitoring Oncology Therapy Universal prophylaxis Monitoring Nephrology Therapy Monitoring Monitoring Solid organ transplants Therapy Universal prophylaxis Monitoring Liver transplantation Therapy Universal prophylaxis Monitoring Rheumatology (+IBD) Therapy Universal prophylaxis or Monitoring Monitoring HIV Therapy Universal prophylaxis^ or ^^Monitoring Monitoring high risk low risk ^ ART+ ^^ ART *BMT and/or Rituximab Marzano DLD 2007.

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8 Screening recommendations (2015) The AASLD strongly recommends that all patients undergoing chemotherapy, immunosuppressive therapy, HSCT, or solid organ transplantation be screened for active or prior HBV infection by testing for HBsAg and anti HBc in serum. The ASCO recommends that clinicians should screen all patients who are about to undergo immunosuppressive therapies associated with a high risk of HBV reactivation, especially if estimated life expectancy is 1 year. HBsAg and anti HBc tests are recommended for screening before cancer The AGA recommends screening for HBV (HBsAg and anti HBc, followed by a sensitive HBV DNA test if positive) in patients at moderate or high risk who will undergo immunosuppressive drug therapy The AGA suggests against routinely screening for HBV in patients who will undergo immunosuppressive drug therapy and are at low risk. The AGA makes no recommendation for a strategy of HBV DNA monitoring followed by rescue treatment as an alternative to antiviral prophylaxis.

9 Conference sponsored by the American Association for the Study of Liver Disease, with support from the American Academy of Dermatology, the American College of Rheumatology, and the American Society of Clinical Oncology AM Di Bisceglie, Hepatology 2015;61:

10 Recommended algorithm for HBV testing and treatment in patients undergoing immunosuppressive therapy. AM Di Bisceglie, Hepatology 2015;61:

11 Risk Stratification for HBV Reactivation AM Di Bisceglie, Hepatology 2015;61:

12 What Is New and Different? Start antiviral prophylaxis in patients with chronic HBV infection before cancer therapy, and consider antiviral prophylaxis for patients with clinically resolved HBV infection for whom systemic cancer therapies associated with a high risk of HBV reactivation are anticipated. Monitor HBsAg positive/anti HBc positive patients and HBsAg negative/anti HBc positive patients for HBV reactivation resulting from chemotherapy approximately every 3 months, and engage in active comanagement with hepatitis B experts. JP. Hwang et al, J Clin Oncol :

13 Risk adaptive HBV screening and management decision making algorithm for patients with cancer before immunosuppressive therapy JP. Hwang et al, J Clin Oncol :

14 RP Perrillo et al. Gatroenterology 2015; 48:

15 Risk Group RP Perrillo et al. Gatroenterology 2015; 48:

16 RP Perrillo et al. Gatroenterology 2015; 48:

17 RP Perrillo et al. Gatroenterology 2015; 48:

18 RP Perrillo et al. Gatroenterology 2015; 48:

19 Farmaci usati Classi Target Farmaci Oncoemato Onco Reuma Dermo Gastro Anticorpi monoclonali si si si si Si Inibitori di BRAF 1 2 si Inibitori del proteosoma 1 1 Si Inibitori di tirosinchinasi si si si si Inibitori di mtor 1 1 si Antracicline 6 si si Derivati del platino 3 si Si Taxani 4 si Antimetaboliti 3 si si si si si Fluoropirimidine 3 si Alchilanti 10 si si si si Alcaloidi 8 si si Glicopeptidi 2 si si Antimetabilita purinico 7 si si si si si Antimetaboliti 1 si Immunosoppressori 1 si si si Carbamidici 1 si Analoghi dell arsenico 1 si Aramide 1 si Isochinoloni 1 si Cortisone si si si si si

20 Precision Medicine What Is Precision Medicine? Treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations. J. L. Jameson, D.L. Longo, NEJM, June 4, 2015

21 Management of immunosuppressed HBV (overt and occult) carriers: The 5 Key Points 1. Identify chemotherapy or immunosuppresive drugs associated with a risk of HBV reactivation 2. Identify disease associated to high risk of HBV reactivation 3. Identify high risk (overt HBV and occult HBV) patients, 4. Choose the appropriate antiviral drugs 5. Indicate the time of prophylaxis

22 Flow chart decisionale per la profilassi anti HBV dei pazienti che ricevono chemioterapia o terapia immunosoppressiva Responsabili scientifici : Vito Di Marco Alfredo Marzano Pietro Lampertico WEB APP ICEBERG Specialisti: Antonio Russo (Oncologo) Emilio Iannitto (Oncoematologo) Francesco Ciccia (Reumatologo) Leonardo Zichichi (Dermatologo) Coordinatori Fabrizio Bronte (Gastroenterologo) Giuseppe Bronte (Oncologo) Esperto Informatico Marco Stacchitti, Protagon sas Roma