Sunday, October 30, 2016

Side Effects - HCV current DAA therapies

Weekend Reading:
Side Effects - HCV direct-acting antiviral therapy

Welcome to Weekend Reading, today we offer a short review of recent warnings issued for hepatitis C direct-acting antivirals.

Maybe you missed important warnings, here we lay them out for you with links and other important information spanning from April to October.  We end with an article discussing side effects, medical contraindications, viral resistance and cost for patients using current DAAs.

Recent Warning
As you may have read the FDA is now requiring a “black box warning” on certain hepatitis C direct-acting antiviral (DAA) medicines because of the risk of hepatitis B reactivation. Why wasn't this reported during clinical trials? Because people with HBV were excluded from the trials, in case you missed it read all about the warning, here.

Around seven months ago we started learning about the safety issue in both Europe and Japan. In May FiercePharma reported about; Japan's PMDA review - hep B risk link to hep C therapies.

Risk Of Liver Cancer
When meeting highlights were released from Pharmacovigilance Risk Assessment Committee (PRAC) in April, in addition to the hepatitis B re-activation safety review,  the EMA expanded an ongoing review about the risk of liver cancer (hepatocellular carcinoma) coming back in patients who were treated with direct-acting antivirals.

Here is Google's cache, the site was down today, should be back up Monday.

The PRAC also extended the scope of its ongoing safety review of medicines known as direct-acting antivirals (Daklinza, Exviera, Harvoni, Olysio, Sovaldi, Viekirax) used for treating chronic (long-term) hepatitis C (an infectious disease that affects the liver, caused by the hepatitis C virus).

At its previous meeting in March, the Committee had initiated a review following cases of hepatitis B re-activation in patients who have been infected with hepatitis B and C viruses, and who were treated with direct-acting antivirals for hepatitis C.

In April 2016, data from a study became available regarding the risk of liver cancer (hepatocellular carcinoma) coming back in patients who were treated with these medicines. The study suggested that these patients were at risk of their cancer coming back earlier than patients with hepatitis C who were not treated with direct-acting antivirals. The scope of the ongoing review has therefore been extended to also assess the risk of liver cancer with these medicines.

Here is a more in-depth article published in May over at Medscape; EMA Expands Review of New HCV Drugs for Liver Cancer Recurrence
The European Medicines Agency (EMA) has extended the scope of its review of the six direct-acting antivirals approved for use in the European Union for treating chronic hepatitis C virus (HCV) infection to include the risk for early liver cancer recurrence, the agency said today. They are daclatasvir (Daklinza, Bristol-Myers Squibb), dasabuvir (Exviera, AbbVie), sofosbuvir/ledipasvir (Harvoni, Gilead Sciences), simeprevir (Olysio, Janssen), sofosbuvir (Sovaldi, Gilead Sciences), and ombitasvir/paritaprevir/ritonavir (Viekirax, AbbVie).
Continue reading...

Liver Cancer - The International Liver Congress 2016
April 13-17 in Barcelona, Spain
Two studies presented during the International Liver Congress suggest that patients with a history of hepatocellular carcinoma have the highest risk of developing a tumor after direct-acting antiviral therapy, but new diagnoses were also reported.

"I do not think that direct-acting antivirals are directly responsible," said lead investigator Stefano Brillanti, MD, from the University of Bologna, Italy.

"The hypothesis is that immune surveillance may be reduced too rapidly," he told Medscape Medical News. "You have an immediate drop in viremia, but also attenuation of inflammation. I think inflammation is a bad thing in terms of hepatitis progression, but it may be a good thing in terms of controlling cancer."
Read the article, also reported by Medscape.

Additional Reading
Liver Cancer After Treatment For Hepatitis C

Side effects, medical contraindications, viral resistance and cost for patients using current DAAs
October 23, 2016
Emerging complexities with HCV DAA regimens: Less is still way more. 
The arrival of interferon-free direct acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) infection have been transformative. Treatment approaches which were once marred by frequent and potentially severe side effects, lack of patient and provider acceptance and marginal efficacy have been replaced by DAA regimens which can cure the vast majority of patients in 12 weeks with minimal to no side effects. Despite these tremendous advances in HCV therapy providers must recognize, as with any medication, that severe side effects and medical contraindications still exist for certain populations when using current DAA therapies. ​

The Changing HCV Landscape: Update on Treatment
Review Article
OCTOBER 26, 2016
DAAs for HCV infection have all but replaced IFN as the foundation of treatment for HCV across all genotypes. Among the major advantages of these oral regimens, beyond their remarkable efficacy, has been their relatively clean safety profile. Adverse effects are common but generally mild, including headache, fatigue, and insomnia—and are trivial relative to the effects of earlier regimens, reflected by a low rate of discontinuation for adverse events. Clinicians must be aware of potential drug–drug interactions, and should prescribe these medications with a commitment toward mastering these and/or consulting the numerous published and online references, including package inserts, containing this information...
Continue to article....

My Journey
In 1999 I began my own HCV journey, it ended with eradicating the virus, today I am still cured. With that said, the side effects were many, still I do not regret my decision.

We have come a long way in developing cures for hepatitis C, today HCV can be cured in most patients, some in 8-12 weeks. Yes, even with fewer side effects.

For people with cirrhosis, or waiting on a transplant list these new drugs are nothing short of a miracle. For the rest of us, its still pretty much a miracle.

Wishing you all a safe and successful journey.


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