HCV Guidelines: A Living Breathing Document

The guidelines for hepatitis C have been updated twice in the month of August.

The first update incorporated the approval of daclatasvir (Daklinza, Bristol-Myers Squibb) in the United States and, based on that approval, modified treatment recommendations for most of the treatment groups. This update came on the heels of a June 2015 update that incorporated the recently presented data from the EASL meeting in Vienna, which Ira Jacobson, MD, discussed in last month’s editorial.

The largest impact of the daclatasvir approval is on the treatment of genotype 3. It was becoming clear that with many of the available direct-acting agents showed great activity against genotype 1a and 1b and to some degree, genotype 4, genotype 3 was becoming the one particular area where our options were more limited. Based on data presented at EASL, there was even a suggestion that a PEG-IFN-based regimen for certain patients with genotype 3 might be the best option. With the approval of daclatasvir, an all-oral regimen consisting of sofosbuvir (Sovaldi, Gilead Sciences) and daclatasvir now is a viable option for patients and practitioners.

There’s a fair degree of data to support the use of daclatasvir and sofosbuvir in the treatment of other genotypes as well, and the guidelines have added daclatasvir as a treatment option to genotype 1 and 2 though there were not enough data to recommend daclatasvir for genotype 4.

Daclatasvir has been available in Europe for well over a year and a half, so these new additions to the HCV guidelines apply mostly to those of us in the United States, though they do codify for those who use the drug in Europe.

Another new formulation of some of the Abbvie drugs, consisting of parataprevir/ritonavir plus ombitasvir (Technivie), also was recently approved, but there was no need to modify the HCV Guidelines, per se, since these two drugs were already a recommended regimen for genotype 4.

The second update to the guidelines that came out on August 20 was a cost effectiveness section. It should be clear that the purpose of publishing this particular section was to provide information to providers regarding cost effectiveness, including definition of terms and methodologies. There’s a lot of discussion in the lay literature and patients often ask questions about cost effectiveness. Sometimes providers are approached by payers to comment on cost effectiveness when we try to advocate for access to certain drugs and the payers claim that the regimen is not cost effective.

The guidelines committee felt it was important to get information out there so providers would understand the principles of cost effectiveness and be conversant on the topic. The new section contains a table that defines commonly used acronyms, such as QALY and ICER, which I discussed in our July editorial.

The cost effectiveness update basically is a primer for those who haven’t thought much about cost effectiveness literature.It straightens out the terminology and explains how these data are generated. It then reviews some of the cost effectiveness data that exists for different genotypes and approved therapies.

It’s important to underscore, however, that cost data and cost effectiveness data are not used by the guidelines committee to make recommendations on treatment.

Treatment recommendations are made in isolation of cost or cost effectiveness.  Recommendations are made as if a panel member answering a phone call from a colleague with a consult on a patient, asking “What would you recommend I do for this patient?”

These updates continue to exemplify the incredible value of having the guidelines exist as a “living document” online. At this point, if you’re giving a talk or writing a review of current treatments of hepatitis C, your recommendations run the risk of being highly out of date at the time of your talk or publication of your paper.

The best thing to do is to reference the HCV Guidelines webpage because the guidelines are updated so frequently and rapidly. For example, when AbbVie released their 3D drugs in December, the guidelines were updated within 5 days of FDA approval. Within 2 weeks of daclatasvir approval, the guidelines were updated again.

This is part of the mission of the guidelines panel and, so far, the group has achieved its mission in remarkable fashion.