1. 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 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 and
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.