http://www.gastro.org/user-assets/Documents/08_Publications/GI_Hep_News/GIHEP_0309.pdf
Triple Therapy Effective In Chronic Hepatitis C
BY ROBERT FINN - Elsevier Global Medical News
Patients with chronic hepatitis C who receive triple therapy with nitazoxanide, peginterferon, and ribavirin show significantly better virologic response rates than do those given standard care, reported Dr. Jean-François Rossignol
and his colleagues in an article appearing in the March 2009 issue of Gastroenterology. The randomized, placebocontrolled,
phase II study included 96 treatment-naive patients with hepatitis C virus (HCV) infection who were divided into three treatment groups. A sustained virologic response (SVR) rate of 79% was achieved with triple therapy, compared with 50% for patients on standard therapy with peginterferon alfa-2a and weightbased ribavirin, a significant difference. A third group received nitazoxanide and peginterferon; 61% achieved SVR, but this was not significantly higher than the
rate for standard therapy.
Nitazoxanide is an anti-infective compound in the thiazolide class and is approved in the United States for treatment of
Cryptosporidium parvum and Giardia lamblia. Dr. Emmet B. Keeffe, AGAF, the senior author on the study, commented in an interview, “An interesting observation was that the use of nitazoxanide in the dual and triple treatment arms was associated with reduced relapse rates (3 of 20 patients and 1 of 23 patients, respectively) compared with the standard-of-care arm (10 of 30 patients).” Dr. Keeffe is vice president and chief medical officer of Romark Laboratories LC and professor of medicine emeritus, Stanford University Medical Center, Palo Alto, Calif. Dr. Rossignol is chairman and chief science officer of Romark Laboratories LC, which markets nitazoxanide under the brand name Alinia. Romark also provided funding for the study.
Triple therapy also proved superior to standard therapy for achieving a rapid virologic response (defined as undetectable
HCV RNA at week 4 of the 48-week study). Of patients in the triple therapy group, 64% achieved a rapid virologic response, compared with 38% of patients in the standard therapy group, a significant difference. In addition, 54% of those who received dual therapy (peginterferon plus nitazoxanide) achieved rapid virologic response, but this was not significantly different from the other groups. “These results demonstrate that nitazoxanide, a novel protein kinase inducer,
has the potential to not only increase the SVR rate but potentially shorten the duration of therapy,” the authors
wrote. The study, conducted at two centers in Egypt, involved patients aged 18 years and older (mean age, 39 years) who had chronic hepatitis C; 92% were male and 97% were white. All patients had both anti-HCV and detectable serum HCV RNA for at least 6 months. Additionally, all had liver biopsies with findings compatible with hepatitis C. All patients were infected with HCV genotype 4. The standard-of-care group received 180 mcg of peginterferon alfa-2a once
weekly and weight-based ribavirin (1,000 mg daily for patients weighing less than 75 kg or 1,200 mg for those weighing
more than 75 kg) for 48 weeks. The dual-therapy group received 500 mg of oral nitazoxanide twice daily for 12 weeks in the lead-in phase, followed by continued nitazoxanide and peginterferon alfa-2a for an additional 36 weeks. The triple-therapy group started with the same 12-week nitazoxanide lead-in phase, followed by 36 weeks of peginterferon alfa-2a and ribavirin. The decision to use a lead-in phase was based on initial pilot experience showing greater antiviral efficacy when nitazoxanide was administered before peginterferon, rather than simultaneously. The investigators explained, however, that the required duration of the lead-in phase remains unknown. They chose 12 weeks to be conservative, but a subsequent study suggested that 4 weeks may be adequate. In addition to rapid virologic response and SVR, the investigators measured complete early virologic response and end-of-treatment response, but there were no significant differences among the groups on those measures.
The authors were unable to attribute any adverse events to the nitazoxanide. The most common adverse events were
anemia, thrombocytopenia, and neutropenia, all of which are common reactions to peginterferon and ribavirin.
The study was stimulated by earlier observations that some patients with cryptosporidiosis and AIDS who were also infected with HCV or HBV had reductions in serum alanine aminotransferase while on long-term nitazoxanide therapy. Also,
in preclinical studies, nitazoxanide showed potent inhibition of HCV replication at low concentrations. ■
В статията се съобщава за резултата от изследване, проведено върху пациенти с хепатит С - генотип 4, лекувани с peginterferon + рибавирин + nitazoxanide, който е във фаза 2 на клиничните изпитвания.
Съобщава се за постигнат продължителен вирусологичин отговор при 79% от пациентите, лекувани с трите препарата, срещу 50% при нормално прилаганата терапия с пегилиран интерферон+рибавирин!
Nitazoxanide в момента е във фаза II клинични проучвания за лечение на хепатит С, в комбинация с peginterferon алфа-2а и рибавирин. [3] [4] -
(http://hepactive.org/sites/default/files/triple_therapy.jpg)