Is response-guided therapy being applied in the clinical setting? The hepatitis C example.

Response-guided therapy (RGT) is a treatment paradigm that bases adjustments to therapeutic regimens on individualized patient physiologic response. Depending on a patient's measured response to a drug, dosing may need to be adjusted accordingly or the therapy may need to be stopped altogether if the continuation of that treatment is deemed futile. As personalized medicine and waste reduction become mainstays of drug therapy, RGT is progressively being utilized in pharmacologic regimens for diseases such as breast cancer and acute myeloid leukemia. The implementation of an RGT approach to drug therapy has been used with boceprevir and telaprevir, and is being investigated with simeprevir in the treatment and management of chronic hepatitis C caused by persistent hepatitis C virus (HCV) infection.1 An understanding of how RGT is being applied in clinical practice is paramount for realizing the potential benefits of the approach. In 2011, boceprevir and telaprevir, each in combination with pegylated interferon and ribavirin, became first-line recommended treatments for HCV genotype 1a,2 based on clinical trials demonstrating an increase in sustained virologic response of approximately 40% to 50% with the combination of pegylated interferon and ribavirin,3–5 to upwards of approximately 65% to 75% with the triple therapy regimen.6–9 Sustained virologic response is defined as an undetectable HCV viral load, typically measured 24 weeks after the completion of treatment, an end point that is associated with the long-term clearance of HCV, improved morbidity, and improved mortality.10–12 In late 2013, the US Food and Drug Administration (FDA) approved sofosbuvir and simeprevir for the treatment of patients with HCV.13,14 Clinical trials with sofosbuvir suggested that 80% to 90% of patients should have undetectable virus levels 12 weeks after completing treatment.15 Clinical trials with simeprevir showed similar results, with almost 80% of patients showing undetectable HCV RNA levels after 12 weeks.16 Accordingly, in 2014, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America released treatment guidelines recommending sofosbuvir for all patients with HCV, except those with severe renal impairment.17 Two additional drugs were approved by the FDA in 2014 for the treatment of HCV infection—the combination of ledipasvir and sofosbuvir, and the combination of ombitasvir, paritaprevir, and ritonavir plus dasabuvir.18,19 In the short term, the utilization of older agents may continue at some level, because of individual patient needs and the cost of newer therapies, among other factors.20 As health plans, pharmacy benefit managers, and other payers continue to define their clinical protocols in the rapidly changing environment of hepatitis C, and as RGT is used increasingly in other therapeutic areas, an evaluation of the adherence to RGT in the clinical management of HCV is necessary. This study measured adherence to the RGT guidelines and treatment futility rules for patients with chronic HCV based on the product labeling information for boceprevir and for telaprevir.21,22 KEY POINTS ▸ Response-guided therapy (RGT) adjusts pharmacologic regimens based on an individual patient's physiologic response ▸ The benefits of RGT include improved clinical outcomes, reduced unnecessary drug exposure for the patient, and the avoidance of unnecessary costs ▸ This study investigated adherence to HCV RNA monitoring guidelines, using a large database for a commercial- and Medicare-insured population ▸ HCV RNA monitoring guidelines were followed in 1 of 3 patients, and adherence to treatment futility rules was less than 55% in patients with HCV infection ▸ This finding highlights the need for the improved implementation of RGT guidelines, which are increasingly being used in specialty pharmacy therapeutics for different conditions, including breast cancer and acute myeloid leukemia ▸ Strategies that increase the use of RGT may in turn improve patient care and reduce unnecessary healthcare expenditures