1. www.company.com 내과 R2 이지훈 N Engl J Med 2014;371:1121-1130

2. www.company.com INTRODUCTION TUBERCULOUS PERICARDITIS –Common cause of pericardial effusion, cardiac tamponade, and constrictive pericarditis –Often have concomitant HIV infection –High mortality and morbidity

3. www.company.com INTRODUCTION Glucocorticoid Therapy –Attenuate the inflammatory response –May improve outcomes and decrease the risk of death by reducing cardiac tamponade and pericardial constriction –May increase the risk of cancer in HIV-infected patients –Scant evidence of the effects of adjunctive glucocorticoid therapy for tuberculosis Mycobacterium indicus pranii immunotherapy –May reduce inflammation associatede with tuberculosis –Increase the CD4+ T-cell count in HIV-infected patients –Shown clinical benefit when administered as a heat-killed intradermal formulation in patients with leprosy –May have benefits in patients with pulmonary tuberculosis and HIV infection

4. www.company.com METHODS STUDY DESIGN –2-by-2 factorial design (IMPI Trial Study)

5. www.company.com METHODS ENROLLMENT CRITERIA

6. www.company.com METHODS

7. www.company.com METHODS STUDY PROCEDURES 1 st week 120mg/d 2 nd week 90mg/d 3 rd week 60mg/d 4 th week 30mg/d 5 th week 15mg/d 6 th week 5mg/d Time of enrollment 2 weeks 4 weeks 6 weeks 3 months

8. www.company.com METHODS OUTCOMES –Primary efficacy outcome Composite of death First occurrence of cardiac tamponade requiring pericardiocentesis or constrictive pericarditis –Secondary efficacy outcome Death Cardiac tamponade Constrictive pericarditis Hospitalization –Safety outcomes Opportunistic infections and cancer Effect of interventions on the CD4+ T-lymphocyte cell count Incidence of the immune reconstitution inflammatory syndrome (in HIV-infected patients)

9. www.company.com RESULTS STUDY POPULATION Jan 2009~Feb 2014 Total 1400 patients

10. www.company.com RESULTS TREATMENT REGIMENS AND ADHERENCE –88.5% vs. 88.7% (prednisolone vs. placebo) –75.9% vs. 81.4% (M. indicus pranii vs. placebo) –Antituberculosis treatment : 76.6% –Antiretroviral treatment : 14.5%

11. www.company.com RESULTS PREDNISOLONE COMPARISON Pericarditis 23.8% Disseminated tuberculosis 18.6% HIV infection 7.3% Other cardiovascular causes 5.7%

12. www.company.com RESULTS M. INDICUS PRANII COMPARISON

13. www.company.com RESULTS PREDNISOLONE AND M.INDICUS PRANII INTERACTION AND SUBGROUP ANALYSES

14. www.company.com RESULTS PREDNISOLONE AND M.INDICUS PRANII INTERACTION AND SUBGROUP ANALYSES

15. www.company.com RESULTS PREDNISOLONE AND M.INDICUS PRANII INTERACTION AND SUBGROUP ANALYSES

16. www.company.com RESULTS SAFETY OUTCOMES

17. www.company.com DISCUSSION Adjunctive therapy with prednisolone for 6 weeks and with M. indicus pranii for 3 months did not have a significant effect on the combined outcome of death from all causes, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. Both therapies were also associated with an increased risk of HIV associated cancer. The use of adjunctive glucocorticoids reduced the incidences of pericardial constriction and hospitalization. The beneficial effects of prednisolone with respect to pericardial constriction and hospitalization were similar in HIV-positive and HIV-negative patients.