The Impact of Direct Acting Antiviral (DAA) Therapy on Renal Function in Diabetic Patients with Hepatitis C Virus (HCV) Chikezie Okoro, PharmD student1; Janet Gripshover, CRNP2; T. Joseph Mattingly II, PharmD, MBA1 1University of Maryland School of Pharmacy; 2University of Maryland Medical Center
Background • The beneficial effects of direct acting antiviral (DAA) therapy on patients with Hepatitis C virus (HCV) infection has been well documented with high rates of virologic suppression and minimal occurrences of therapylimiting side effects .1 • Antiviral treatment has also been correlated with an improvement in renal outcomes in diabetic patients with hepatitis C virus. 2, • Hepatitis C virus has been associated with the development of chronic kidney disease.3 • However, it is still unclear if DAA’s should be used in hepatitis C patients with moderate to severe renal impairment as some of the DAA’s are renally eliminated.1,4 • The lack of evidence has prevented an established treatment guideline in this patient population
Results Table 1: Sample patient characteristics. Characteristics Sample Size
Cohort
Discussion/Limitations
Figure 1: Changes in renal function from baseline to 12 weeks post completion of therapy 140
%
120
75
Sex
100
Male
45
60.0
Female
30
40.0
White
15
20.0
40
Black
55
73.3
Other
5
6.7
20
Age (SD)
61 (8)
Race
80
Crea\nine Clearance (mL/min)
60
0
Mean at Baseline
Genotype
Objectives • The primary objective of this retrospective pilot study was to examine the effects of direct acting antiviral treatment on renal function in hepatitis C virus patients with diabetes • The secondary objective was to determine the effects of direct acting antiviral treatment on blood glucose control in diabetic patients
Methods • Pilot case control study • Inclusion Criteria: Diabetic patients aged 18-89 at the UMMC hepatology clinic, who completed interferon-free antiviral hepatitis C treatment including Harvoni, Viekira Pak, or Olysio/Sovaldi. • Exclusion Criteria: Patients who did not obtain the pertinent lab results at the treatment checkpoints • All patient data was obtained using the electronic health record software, Epic. • Variables included sex, race, age, METAVIR score, HCV Regimen, previous treatment, treatment duration, and SVR 12. • Treatment checkpoints included the beginning of treatment (baseline), at weeks 4, 8, and 12, and at SVR12 • Statistical tests of significance used to analyze the study results included the p-value and the confidence interval • Analyzed using SAS Version 9.4 • Approved by University of Maryland Baltimore Institutional Review Board
1a
50
66.7
1b
20
26.7
Other
5
6.7
Mean at SVR12
Figure 2: Changes in blood glucose control from baseline to 12 weeks post completion of therapy
METAVIR Score
10
F0
12
16.0
F1
12
16.0
F2
11
14.7
F3
10
13.3
F4
28
37.3
Missing
2
2.7
HARV
58
77.3
SIM/SOF
8
10.7
6
8.0
Other
3
4.0
Treatment Naïve Naïve
60
80.0
Experienced
15
20.0
Conclusions
6
Hemoglobin A1c (%)
• This study demonstrated no association between existing direct acting antiviral therapies and impact on renal function in patients with diabetes • No statistically significant changes in diabetic treatment outcomes were observed in patients undergoing HCV treatment with DAAs
4
2
0
Mean at Baseline
Mean at SVR12
Table 2: Changes from baseline to 12 weeks post completion of therapy.
Treatment DuraCon 8 weeks
5
6.7
12 weeks
56
74.7
Serum Blood Glucose
24 weeks
14
18.7
Serum Crea\nine
Yes
54
72.0
Crea\nine Clearance
No
1
1.3
Unknown
20
26.7
SVR12
Limitations • Incomplete lab data throughout the treatment period limited the number of patients who were able to be included in the study • Medication adherence was not assessed, which could have impacted renal outcomes and blood glucose control • The patients examined in this study primarily had HCV genotype 1, limiting the generalizability of this study to all HCV genotypes
8
HCV Regimen
VIEK
• The safety and efficacy of DAA treatment that contain renally excreted metabolites (eg. sofosbuvir) in patients infected with HCV with moderate to severe renal impairment has not been established.1,4 • One of the clinical trials that led to the recent approval of elbasvir/ grazoprevir, the C-SURFER trial, showed that this new DAA was both safe and effective in this patient population as there are no renally excreted components.4 • Patients included in this study who received HCV treatment with renally active metabolites (Harvoni/Sovaldi) did not exhibit any significant change in renal function throughout treatment. • The lack of a significant worsening of renal function is unexpected as patients with severe renal impairment have been show to exhibit up to a 20-fold increase in the sofosbuvir metabolite exposure.5
Hemoglobin A1c
Presented at the Academy of Managed Care & Specialty Pharmacy Annual Meeting, San Francisco, California, April 20, 2016.
Mean Change from Baseline -‐17
95% Confidence Interval [-‐42, 7]
p-‐value
-‐0.06
[-‐0.14, 0.02
0.14
2.7
[-‐1.6, 6.9]
0.21
-‐0.31
[-‐0.95, 0.34]
0.34
0.15
References 1. Maruyama A, Partovi N, Yoshida EM, et al. A Review of direct-acting antivirals for the treatment of hepatitis C in Patients with Advanced Chronic Kidney Disease. Nephrol Dial Transplant. 2015. 0:1-6 2. Hsu YC, Lin JT, Ho HJ, et al. Antiviral Treatment for Hepatitis C Virus Infection is Associated with Improved Renal and Cardiovascular Outcomes in Diabetic Patients. Hepatology. 2014; 59(4): 1293-1302 3. Butt AA, Wang X, Fried LF. HCV infection and the incidence of CKD. Am J Kidney Dis. 2011. 57(3): 396-402 4. Roth D, Nelson DR, Bruchfield A, et al. Grazoprevir plus elbasvir in treatmentnaïve and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-surfer study): a combination phase 3 study. Lancet. 2015. 386: 1537-1545 5. Harvoni [package insert]. Foster City, CA: Gilead Sciences, Inc; 2015
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