Pulmonary hypertension associated with interferon therapy: A population based study R. Papani, A. G. Duarte, Y-L. Lin, G. Sharma Division of Pulmonary, Critical Care and Sleep Medicine University of Texas Medical Branch - Galveston, TX Background Results Drug induced pulmonary arterial hypertension (PAH) have been associated with exposure to aminorex, fenfluramine, benfluorex, dasatinib, amphetamines & interferon. A case series (Savale L, ERJ 2014) reported development of PAH in 53 patients treated with interferon for 5 - 117 months. A population based assessment of interferon induced pulmonary hypertension has not been reported. Figure 1. Cohort selection in patients with hepatitis C and multiple sclerosis treated with interferon. Table 1. Baseline characteristics of patients in the study cohort. Table 2. Factors associated with the likelihood of developing pulmonary hypertension. Patient characteristics N % Indication for interferon Multiple sclerosis 7190 35.75 Hepatitis C 12923 64.25 Age 20-29 1205 5.99 30-39 3154 15.68 40-49 7526 37.42 50-59 7084 35.22 60-65 1144 5.69 Gender Male 9906 49.25 Female 10207 50.75 Comorbidity Connective tissue disorder 331 1.65 Other liver disease* 2647 13.16 AIDS 268 1.33 Obesity 294 1.46 Hypertension 3612 17.96 Congestive heart failure 86 0.43 Valvular heart disease 156 0.78 Chronic pulmonary disease 750 3.73 Diabetes 1589 7.90 Congenital heart disease 8 0.04 Atrial fibrillation and flutter 74 0.37 Sleep apnea 338 1.68 Patient characteristics Hazard ratio (95% CI) Indication for interferon Multiple sclerosis Reference Hepatitis C 1.43 (0.69, 2.96) Age 20-29 30-39 0.26 (0.02, 4.23) 40-49 1.46 (0.19, 11.19) 50-59 2.41 (0.32, 18.29) 60-65 4.05 (0.49, 33.36) Gender Male Female 1.02 (0.62, 1.68) Comorbidity, Yes versus No Connective tissue disorder 4.32 (1.71, 10.96) Other liver disease (Excluding Hep C) 3.21 (1.93, 5.34) AIDS 2.63 (0.63, 10.89) Obesity 0.73 (0.10, 5.51) Hypertension 1.43 (0.84, 2.43) Congestive heart failure 1.10 (0.15, 8.17) Valvular disease 3.76 (1.16, 12.21) Chronic pulmonary disease 1.92 (0.82, 4.50) Diabetes 2.27 (1.25, 4.11) Sleep apnea 1.31 (0.31, 5.56) Patients initiated on α or β interferon therapy between 4/2001 and 12/2012 N= 58,876 Objective Patients with continuous enrollment in the prior year N= 26,212 To determine the incidence of pulmonary hypertension after initiation of interferon therapy in a national population of privately insured patients residing in the U.S. Methods Patients aged between 20 and 65 years N= 25,014 ClinformaticsTM Data Mart (CDM) Database was used to identify subjects between 20 and 65 years who received α or β interferon therapy between 4/2001 and 12/2012. National Drug Codes (NDCs) and Healthcare Common Procedure Coding System (HCPCS) codes were used to identify patients prescribed interferon therapy. Patients with ICD-9 code diagnosis of hepatitis C or multiple sclerosis prescribed interferon therapy were identified. Patients were followed since the first interferon prescription to the initial ICD-9 diagnosis of pulmonary hypertension or disenrollment Pulmonary hypertension was identified with an ICD-9 code 416.0 and 416.8. Age, gender, co-morbidities and PAH medications were recorded. Patients diagnosed with pulmonary hypertension were followed to determine whether PAH specific medications were prescribed. Descriptive statistics were used to examine the group and proportional hazard regression model assessed the factors associated with an ICD-9 diagnosis of pulmonary hypertension. Statistical analysis was performed with SAS version 9.3 (SAS Inc., Cary, NC). Patients not diagnosed with pulmonary hypertension prior to interferon treatment N= 24853 Limitations Patients with diagnosis of hepatitis C or multiple sclerosis in the prior 3 months N= 20,113 Cohort follow up period may not have allowed identification of all subjects prescribed interferon who developed pulmonary hypertension. A diagnosis of pulmonary hypertension and subsequent prescription of PAH-medications was based on ICD-9/drug codes. We identified 20,113 subjects prescribed interferon with a diagnosis of either hepatitis C or multiple sclerosis (Figure 1). Females comprised 50.8% of the group and 78% were > 40 years of age. Hepatitis C was the primary indication for interferon therapy in 64.3% of the cohort . Mean follow up was 29.5 ±27.4 months (median 20 months) 71 (0.35%) subjects had an ICD-9 code diagnosis of pulmonary hypertension. In the group with an ICD-9 code diagnosis of pulmonary hypertension (n=71), PAH specific medications were prescribed to 7 patients (9.9%). Factors associated with development of pulmonary hypertension were: Connective tissue disorder, other liver disease (excluding hepatitis C), valvular heart disease and diabetes (Table 2). Conclusion In this U.S. population claims study, development of pulmonary hypertension in patients with hepatitis C or multiple sclerosis treated with interferon was a rare event.