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No Difference in Effectiveness of 8 vs 12 Weeks of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C in Black Patients

Published:March 10, 2018DOI:https://doi.org/10.1016/j.cgh.2018.03.003

      Background & Aims

      Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen.

      Methods

      We conducted an observational study of Kaiser Permanente Northern California members with HCV genotype 1 infection who were eligible for 8 weeks of treatment with ledipasvir and sofosbuvir (treatment-naïve, no cirrhosis, no HIV infection, level of HCV RNA <6 million IU/mL) and were treated for 8 or 12 weeks from October 2014 through December 2016. We used χ2 analyses to compare sustained virologic response 12 weeks after the end of treatment (SVR12) among patients treated for 8 vs 12 weeks, and adjusted Poisson models to identify factors associated with receipt of 12 weeks of therapy among patients eligible for 8 weeks.

      Results

      Of 2653 patients eligible for 8 weeks of treatment with ledipasvir and sofosbuvir, 1958 (73.8%) received 8 weeks of treatment and 695 (26.2%) received 12 weeks; the proportions of patients with SVR12 were 96.3% and 96.3%, respectively (P = .94). Among 435 black patients eligible for the 8-week treatment regimen, there was no difference in the proportions who achieved an SVR12 following 8 vs 12 weeks’ treatment (95.6% vs 95.8%; P = .90). Male sex, higher transient elastography or FIB-4 scores, higher INR and level of bilirubin, lower level of albumin, obesity, diabetes, and ≥15 alcohol drinks consumed/week were independently associated with receiving 12 weeks of treatment among patients eligible for the 8-week treatment regimen, but were not associated with reduced SVR12 after 8 weeks of treatment.

      Conclusion

      In an observational study of patients who received ledipasvir and sofosbuvir treatment for HCV genotype 1 infection, we found that contrary to guidelines, 8-week and 12-week treatment regimens do not result in statistically significant differences in SVR12 in black patients. Patient characteristics were associated with receipt of 12-week regimens among patients eligible for 8 weeks, but were not associated with reduced SVR12 after 8 weeks. Shorter treatment courses might therefore be more widely used without compromising treatment effectiveness.

      Keywords

      Abbreviations used in this paper:

      AASLD (American Association for the Study of Liver Diseases), CI (confidence interval), HCV (hepatitis C virus), HIV (human immunodeficiency virus), ICD (International Classification of Diseases), IDSA (Infectious Diseases Society for America), KPNC (Kaiser Permanente Northern California), LDV/SOF (ledipasvir/sofosbuvir), RR (risk ratio), SVR (sustained virologic response)
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      References

        • Kowdley K.V.
        • Gordon S.C.
        • Reddy K.R.
        • et al.
        Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis.
        N Engl J Med. 2014; 370: 1879-1888
        • Afdhal N.
        • Reddy K.R.
        • Nelson D.R.
        • et al.
        Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.
        N Engl J Med. 2014; 370: 1483-1493
        • Afdhal N.
        • Zeuzem S.
        • Kwo P.
        • et al.
        Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.
        N Engl J Med. 2014; 370: 1889-1898
      1. Food and Drug Administration. Prescribing information for HARVONI. 2014. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205834s000lbl.pdf. Accessed December 13, 2017.

      2. Recommendations for testing, managing, and treating hepatitis C. 2017. Available at: http://www.hcvguidelines.org. Accessed September 27, 2017.

      3. Marcus JL, Hurley LB, Chamberland S, et al. Disparities in initiation of direct-acting antiviral agents for hepatitis C virus infection in an insured population. Public Health Rep. [In press].

        • Wilder J.M.
        • Jeffers L.J.
        • Ravendhran N.
        • et al.
        Safety and efficacy of ledipasvir-sofosbuvir in black patients with hepatitis C virus infection: a retrospective analysis of phase 3 data.
        Hepatology. 2016; 63: 437-444
        • Su F.
        • Green P.K.
        • Berry K.
        • et al.
        The association between race/ethnicity and the effectiveness of direct antiviral agents for hepatitis C virus infection.
        Hepatology. 2017; 65: 426-438
        • O'Brien T.R.
        • Lang Kuhs K.A.
        • Pfeiffer R.M.
        Subgroup differences in response to 8 weeks of ledipasvir/sofosbuvir for chronic hepatitis C.
        Open Forum Infect Dis. 2014; 1 (ofu110)
        • Ioannou G.N.
        • Beste L.A.
        • Chang M.F.
        • et al.
        Effectiveness of sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir regimens for treatment of patients with hepatitis C in the Veterans Affairs National Health Care System.
        Gastroenterology. 2016; 151: 457-471 e455
        • Backus L.I.
        • Belperio P.S.
        • Shahoumian T.A.
        • et al.
        Real-world effectiveness and predictors of sustained virological response with all-oral therapy in 21,242 hepatitis C genotype-1 patients.
        Antivir Ther. 2017; 22: 481-493
        • Backus L.I.
        • Belperio P.S.
        • Shahoumian T.A.
        • et al.
        Real-world effectiveness of ledipasvir/sofosbuvir in 4,365 treatment-naive, genotype 1 hepatitis C-infected patients.
        Hepatology. 2016; 64: 405-414
        • Backus L.I.
        • Belperio P.S.
        • Shahoumian T.A.
        • et al.
        Comparative effectiveness of ledipasvir/sofosbuvir +/- ribavirin vs ombitasvir/paritaprevir/ritonavir + dasabuvir +/- ribavirin in 6961 genotype 1 patients treated in routine medical practice.
        Aliment Pharmacol Ther. 2016; 44: 400-410
        • Kowdley K.V.
        • Sundaram V.
        • Jeon C.Y.
        • et al.
        Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection.
        Hepatology. 2017; 65: 1094-1103
      4. Gordon N. Similarity of the adult Kaiser Permanente membership in Northern California to the insured and general population in northern California: statistics from the 2011 California Health Interview Survey. 2015. Available at: https://divisionofresearch.kaiserpermanente.org/projects/memberhealthsurvey/SiteCollectionDocuments/chis_non_kp_2011.pdf. Accessed September 27, 2017.

      5. Heading off and helping with unhealthy alcohol use. 2014. Available at: https://share.kaiserpermanente.org/article/heading-off-and-helping-with-unhealthy-alcohol-use/. Accessed August 11, 2017.

        • Silverberg M.J.
        • Chao C.
        • Leyden W.A.
        • et al.
        HIV infection and the risk of cancers with and without a known infectious cause.
        AIDS. 2009; 23: 2337-2345
        • Karter A.J.
        • Ferrara A.
        • Liu J.Y.
        • et al.
        Ethnic disparities in diabetic complications in an insured population.
        JAMA. 2002; 287: 2519-2527
        • Holmberg S.D.
        • Lu M.
        • Rupp L.B.
        • et al.
        Noninvasive serum fibrosis markers for screening and staging chronic hepatitis C virus patients in a large US cohort.
        Clin Infect Dis. 2013; 57: 240-246
        • Bonder A.
        • Afdhal N.
        Utilization of FibroScan in clinical practice.
        Curr Gastroenterol Rep. 2014; 16: 372
        • Li J.
        • Gordon S.C.
        • Rupp L.B.
        • et al.
        The validity of serum markers for fibrosis staging in chronic hepatitis B and C.
        J Viral Hepat. 2014; 21: 930-937