US physicians have backed prioritising the sickest patients for treatment with the expensive new generation of oral hepatitis C antivirals, in line with coverage policies enforced by insurers. Guidelines drawn up by the American Association for the Study of Liver Disease (AASLD) have put the highest emphasis on patients with cirrhosis and others likely to suffer imminent complications while suggesting that those without signs of progression can wait.
In a position that, if followed, would thrust new costs onto public health programmes, the specialists also supported treatment of patients at high risk of transmission, such as intravenous drug users and prisoners. This position could be unpopular among lawmakers looking at the $1,000-a-pill pricetag of Gilead Sciences’ Sovaldi, but health economists argue that it is an efficient way to limit spread of the virus.
Warehousing by any other name
The recommendations are contained in a new chapter of broader hep C guidelines drawn up by the AASLD and the Infectious Diseases Society of America entitled “When and In Whom To Initiate HCV Therapy”. As the costs of treatments have proved too prohibitive to offer the newest treatments to 3.2 million Americans and at least 130 million people around the world who have chronic infections, physicians and payers have debated how to prioritise the use of Sovaldi and the competing drug Olysio, from Johnson & Johnson and Medivir.
In one sense, little has changed from what preceded the advent of oral direct-acting antivirals. The mainstay treatments interferon and ribavirin were accompanied by flu-like symptoms as well as neuropsychiatric side effects, and thus hep C patients were typically unwilling to initiate a therapy that could last up to a year unless their disease was progressing – this staging was called “warehousing”.
The difference now is that payers have imposed warehousing on the basis of cost, and physicians appear to agree that this is acceptable because of limited resources. The new drugs have a much shorter course and in some cases interferon is no longer needed, so patients are more willing to try them.
Progression can take decades, and the risk increases with age, thus the cost-benefit analysis tilts more in favour of treatment in a patient suffering with advancing fibrosis, whose medical care will only get more expensive as time passes. This can escalate to annual costs that rival the onetime $84,000 pricetag of a course of Sovaldi (Vantage point – Huge hep C costs prompt search for when and where to treat, August 6, 2014).
The guideline says the “highest priority” should be put on patients at the greatest risk of liver-related complications. It specifically names those with advanced fibrosis or compensated cirrhosis – corresponding to a Metavir score of F3 or F4 – along with liver transplant recipients and patients with infections that have complications outside the liver.
IV drug users, men who engage in high-risk sexual practices with other men, prisoners, and patients on long-term dialysis are also prioritised because of the risk of transmission. At least 30% of the two million American prisoners are thought to be chronically infected, and 90% of prisoners are in state or local facilities, so the costs of this treatment will fall largely to state budgets.
State budgets are also likely to be affected by recommendations to treat IV drug users, as many will qualify for Medicaid or other government-backed public health programmes. Eliminating the virus in this population, coupled with needle exchange schemes, has been cited as a cost-efficient approach to reducing disease prevalence.
The guideline does not explicitly support withholding care to patients outside those identified as highest priority. However, its use of terms like “available resources” and recognition that treatment can be deferred is a clear acknowledgement of cost-constrained reality and the eye-watering costs of the new drugs.
In those patients who do not qualify for treatment, the guideline calls for ongoing assessment of disease progression using tissue biopsies or non-invasive procedures such as liver elastography combined with biomarker tests. This analysis should be augmented by incorporating other risk factors, including age, obesity and alcohol consumption – the last of these is the biggest non-biological indicator of disease progression, according to experts who have studied the disease.
Experts in the field have been holding out hope that increased competition in the space will bring down prices sufficiently to expand treatment to what is now the lower-priority infected population – AbbVie, Merck & Co and Bristol-Myers Squibb all have rivals queued up to take on the current champion. Whether market forces can be strong enough to allow for massive takeup of hepatitis C antivirals is an open question. Hepatologists surely would like to throw out this chapter of their guidelines and treat everyone.