Direct acting antivirals not associated with higher rates of adverse liver, kidney, cardiovascular events.
Oakland, CA — Direct acting antiviral agents used to treat patients with the hepatitis C virus are not associated with higher rates of adverse liver, kidney, and cardiovascular events, according to Kaiser Permanente-led research published today in JAMA Network Open.
This research contributes to the literature on the safety of a newer class of medications for treating hepatitis C virus, according to the study’s lead author Elizabeth A. McGlynn, PhD, vice president for Kaiser Permanente Research and executive director of the Kaiser Permanente Center for Effectiveness & Safety Research.
For the 2.4 million Americans currently infected with hepatitis C virus these newer direct acting antivirals that became available in November of 2013 and that can be taken over 8 to 12 weeks with fewer side effects were hailed as a substantial breakthrough in treating patients with hepatitis C virus. A boxed warning from the Food and Drug Administration in 2016 that identified the potential for reactivation of the hepatitis B virus along with an analysis from the Institute for Safe Medication Practices that identified cases of liver injury and liver failure raised concerns about potential safety problems with this new class of medication.
Research scientists from Kaiser Permanente and the University of Florida College of Medicine used rich longitudinal data from 3 National Patient Centered Clinical Research Network systems (from 2012 to 2017) to examine whether patients with hepatitis C virus who received newer direct acting antivirals experienced higher rates of adverse events compared to patients with hepatitis C virus who did not receive these medications.
Among the 33,808 adults who were included in the study from the 3 systems, there was no evidence that those who received direct acting antivirals experienced higher rates of any of the 12 adverse events evaluated than those who did not. Direct acting antiviral exposures were associated with statistically significant lower odds of adverse events in adjusted analyses including death, multiple organ failure, hepatic decompensation, acute-on-chronic liver event, and arrhythmia, explained the authors. Patients who were dispensed direct acting antivirals also had lower rates of hospitalization and emergency department use than those not receiving the new agents. The authors used advanced statistical methods to increase the likelihood that differences in adverse events could reasonably be attributed to differences in medication exposures.
“Because clinical trials enroll relatively small numbers of patients and are commonly conducted with participants who are different than those who receive medications in usual practice, the results of real-world studies like this can contribute to a richer source of information for shared decision-making,” said McGlynn. She added that the study included a higher proportion of patients from racial and ethnic minorities than most trials as well as patients typically excluded from clinical trials such as those with a prior diagnosis of liver cancer, prior liver transplant, cirrhosis, and multiple comorbidities.
“We were able to look at multiple adverse events in a geographically and demographically diverse population and found no evidence that the drugs were associated with higher event rates,” noted senior author David R. Nelson, MD, from the University of Florida College of Medicine. “This study should provide reassurance to patients and clinicians who might be concerned about the safety of this class of medications.”
The study was conducted at Kaiser Permanente in Southern California, which serves 4.5 million members; Kaiser Permanente in Northern California, which serves 4.3 million members; and OneFlorida, whose partners provide care to more than 15 million Floridians. Data sources included enrollment files, encounters across all settings, diagnoses associated with encounters, laboratory studies and results, and pharmacy dispensing.
Additional authors on the study include John L. Adams, PhD, Kaiser Permanente Center for Effectiveness & Safety Research; Jason Kramer, MS, Kaiser Permanente Center for Effectiveness & Safety Research; Amandeep K. Sahota, MD, Kaiser Permanente in Southern California; Michael J. Silverberg, PhD, Kaiser Permanente Division of Research; Elizabeth Shenkman, University of Florida, College of Medicine; and David R. Nelson, University of Florida, College of Medicine.
This research was funded by the Patient Centered Outcomes Research Institute.
Kaiser Permanente is committed to helping shape the future of health care. We are recognized as one of America’s leading health care providers and not-for-profit health plans. Founded in 1945, Kaiser Permanente has a mission to provide high-quality, affordable health care services and to improve the health of our members and the communities we serve. We currently serve more than 12.3 million members in eight states and the District of Columbia. Care for members and patients is focused on their total health and guided by their personal Permanente Medical Group physicians, specialists and team of caregivers. Our expert and caring medical teams are empowered and supported by industry-leading technology advances and tools for health promotion, disease prevention, state-of-the-art care delivery and world-class chronic disease management. Kaiser Permanente is dedicated to care innovations, clinical research, health education and the support of community health.