there have been a slew of articles over the past 2-3 years on non-interferon based therapy for hepatitis c. the latest one in the lancet is prescient in that it actually found a great oral regimen just as the FDA is about to approve a couple of new drugs for hepatitis c (see http://dx.doi.org/10.1016/S0140-6736(13)62121-2). in this open-label drug-company sponsored study 100 patients with hepatitis C infection at the Texas Liver Institute were assigned to 5 different therapies, and assessed for the sustained virologic response 12 weeks after the therapy ended (SVR12). All patients had genotype 1 hepatitis C. Groups 1-3 below consisted of 60 non-cirrhotic treatment-naïve patients and groups 4 and 5 were 40 patients with or without cirrhosis but had previously failed a protease-inhibitor regimen. Patients were given a combination pill of sofosbuvir 400mg qd (a nucleotide polymerase inhibitor hopefully to be released later this week by the FDA) plus ledipasvir 90mg qd (an NS5A inhibitor), with or without ribivarin. The groups and the responses are as follows:
For 60 noncirrhotic treatment-naïve patients
–sofosbuvir plus ledipasivir for 8 weeks: SVR12 in 19 of 20 patients (95%)
–sofosbuvir plus ledipasivir plus ribavirin for 8 weeks: SVR12 in 21 of 21 patients (100%)
–sofosbuvir plus ledipasivir for 12 weeks: SVR12 in 18 of 19 patients (95%)
for 40 patients who had virologic failure after receiving a protease-inhibitor regimen
–sofosbuvir plus ledipasivir for 12 weeks: SVR12 in 18 of 19 patients (95%)
–sofosbuvir plus ledipasivir plus ribavirin for 12 weeks: SVR12 in 21 of 21 patients (100%)
adverse reactions: 48% had at least one adverse reaction, the highest being in those also given ribavirin. The most common adverse effects were nausea, anemia, URI, and headache, most felt to be of only mild severity. Anemia was only noted in those patients on ribavirin. No patient discontinued therapy because of an adverse reaction
in terms of these dramatic responses, there was (not surprisingly) no difference in response by previous treatment history, presence or absence of ribavirin in the regimen, presence or absence of cirrhosis, IL28B genotype, baseline viral load, or race. Almost all patients, however, had genotype 1a (about 85%).
so, really amazing results, adding onto remarkable progress over the past several years. the vast majority of hep c infections in the US are genotype 1, which historically was remarkably resistant to really awful therapy (48 weeks of interferon and ribavirin, which was not only awful in terms of adverse effects and length of therapy — ie, if tolerated, patients basically lost one year of productive life — but also only had a 25% efficacy). this study, if repeated with a larger group of patients with longer followup and at multiple sites, raises the very distinct possibility of patients taking 1 combo pill once a day for 8 weeks and getting rid of hep c completely and without significant adverse effects. pretty dramatic progress.
geoff