내과 R2 이지훈 N Engl J Med 2014;371:

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

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

METHODS STUDY DESIGN –2-by-2 factorial design (IMPI Trial Study)

METHODS ENROLLMENT CRITERIA

METHODS

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

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)

RESULTS STUDY POPULATION Jan 2009~Feb 2014 Total 1400 patients

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%

RESULTS PREDNISOLONE COMPARISON Pericarditis 23.8% Disseminated tuberculosis 18.6% HIV infection 7.3% Other cardiovascular causes 5.7%

RESULTS M. INDICUS PRANII COMPARISON

RESULTS PREDNISOLONE AND M.INDICUS PRANII INTERACTION AND SUBGROUP ANALYSES

RESULTS PREDNISOLONE AND M.INDICUS PRANII INTERACTION AND SUBGROUP ANALYSES

RESULTS PREDNISOLONE AND M.INDICUS PRANII INTERACTION AND SUBGROUP ANALYSES

RESULTS SAFETY OUTCOMES

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.