Adherence to Hepatitis C Therapies and The Impact of Comorbid Conditions

1. Adherence to Hepatitis C Therapies and The Impact of Comorbid Conditions Mary Cassler RPh, MBA, Lon Castle, M.D., Bill Dreitlein, Pharm.D., Mona Khalid, MBA, MPH, Helen Kourlas, Pharm D., and Jane Barlow, M.D., MBA, MPH April 11, 2011 International Conference on Viral Hepatitis 2011

2. Objective • Analyze Hepatitis C patients’ adherence through a large pharmacy database to identify: • Patterns of adherence • Opportunities to improve adherence amongst this population • Other comorbid conditions that affect adherence • Predictors for early treatment discontinuation • Opportunities to avoid side affects associated with HCV therapies

3. Background • Studies show that HCV patients should maintain adherence rates of ≥80-85% in order to receive optimal benefits from HCV therapies1,2 • Suboptimum drug exposure has been shown to be associated with physician-directed dose reductions due to side effects • Little evidence exists to show association of suboptimum drug exposure to missed doses by patients • Common side effects of HCV therapies makes it challenging for patient’s to adhere to HCV regimen • Approximately 20-40% of interferon patients suffer from depression3 • Greater than 50% of patients treated with ribavirin experience a decline in Hb, necessitating a dose reduction4 Source: 1Lo Re, et al. Adherence to Hepatitis C Virus Therapy and Early Virologic Outcomes. CID 20009: 48:186–93 2McHutchinson, et al. Adherence to Combination Therapy Enhances Sustained Response in Genotype-1–Infected Patients With Chronic Hepatitis C. Gastroenterology 2002;123:1061–1069 3 Lui, et al. Impact of Depressive Symptoms and Their Treatment on Completing Antiviral Treatment in Patients With Chronic HepatitisC J Clin Gastroenterol Volume 44, Number 8, September 2010 4Krishnan, et al. Ribavirin-Induced Anemia in Hepatitis C Virus Patients Undergoing Combination Therapy. PLoS Comput Biol. 2011 Feb 3;7(2):e1001072

4. Methodology • A national pharmacy benefit management (PBM) claims database was used to identify patients new to interferon and ribavirin therapies • A one-year review period was used to monitor patients’ claims and 168 days follow-up period was used to calculate their medication possession ratio (MPR) • Adherence to therapy was defined as MPR ≥80% • Comorbidities such as HIV and depression were evaluated to determine their impact on patients’ adherence to HCV therapies

5. Results 3607 HCV Patients Identified: 1657 were being treated for depression 109 were coinfected with HIV 66 of these patients were also being treated for depression 60.4% were adherent to their HCV medications Patients being treated for depression had the highest MPR adherence rates 61.5% depression only 69.7% depression and HIV

6. Patient Counts by Comorbid Conditions Source: Medco Data 2010

7. Definition of adherence Compliance Is the patient taking their medication as prescribed? Are they receiving sufficient daily doses of medication? Persistency Is patient filling medication regularly?  Are there any gaps in therapy? Has the patient dropped off therapy? Adherence Compliance + Persistency

8. Percentage of Patients Compliant to Therapy Source: Medco Data 2010

9. Persistency to Hep-C Therapy Source: Medco Data 2010

10. MPR Impact by Comorbid Conditions Source: Medco Data 2010

11. Interferon adherence by MPR Group Interferon MPR Groups • MPR Groups • 68.5% of interferon patients have MPR ≥80% • ~11% of patients have suboptimal adherence that could be amendable by interventions • Healthcare provider interventions could potentially push them into optimal MPR Source: Medco data, 2010.

12. Ribavirin adherence by MPR Group Ribavirin MPR Groups • MPR Groups • 62.6% of ribavirin patients have MPR ≥80% • Adherence can be influenced by physicians stopping drug due to anemia • ~14% of patients have suboptimal adherence that could be amendable by interventions Source: Medco data, 2010.

13. Conclusions • 40% of patients do not achieve ≥80% adherence rates and therefore risk the development of medication resistance, inadequate viral suppression and disease progression • Patients concurrently receiving antidepressant medications demonstrated higher adherence to HCV therapies • There may be value in identifying and appropriately treating patients with depression. • Proactive monitoring is particularly warranted in patients with HCV, especially considering the established link between IFN therapy and the onset of depressive symptoms. • Identification and treatment of depression may be more important for those with comorbid HIV disease • Effective depression screening by healthcare professionals may be a valuable tool to improve treatment adherence in patients with HCV.

14. Next Steps • Additional studies are needed to validate these findings • Develop a screening tool to identify and evaluate depression in patients receiving HCV therapies and treat them appropriately • Create an adherence program that will identify those patients <80% adherent and incorporate targeted interventions to improve adherence • Design an adherence program that: • incorporates a comprehensive depression screening tool • shares the results of the program with physicians so that they can proactively determine best depression treatment options.