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原始短消息: 请关注硝唑尼特引用:
请关注硝唑尼特这种药,美国一公司用于慢乙肝,表面抗原转阴率达25%,你在美国,可否发邮件或打电话了解一下详细情况呢?
谢回复,谢谢目前有帮助长效干扰治疗HCV的辅助药物。HBV的有人做II期但是都没有消息呢。
HIV and Hepatitis.com Coverage of the
43rd EASL Conference (EASL 2008)
April 23 - 27, 2008, Milan Italy
43rd EASL Conference Main Page
Nitazoxanide Added to Standard Therapy Improves Response in Patients with Genotype 4 HCV: STEALTH-C1 Study
By Liz Highleyman
Nitazoxanide (Alinia) belongs to a new class of small molecules called thiazolides that modulate cell signaling pathways involved in a host cell's innate defense against viruses. This mechanism of action is related to that of interferon, but thiazolides can be administered orally and are not associated with similar side effects.
Nitazoxanide is approved in the U.S. for treatment of gastroenteritis due to Cryptosporidium parvum (cryptosporidiosis) and Giardia lamblia (giardiasis). Preclinical studies have demonstrated that it also exhibits antiviral activity against both hepatitis C virus (HCV) and hepatitis B virus (HBV).
Several presentations at the recent 43rd annual meeting of the European Association for the Study of the Liver (EASL) last month in Milan looked at nitazoxanide for the treatment of hepatitis C.
STEALTH C-1
The discoverer of nitazoxanide, Jean-Francois Rossignol of Romark Laboratories, and colleagues conducted the randomized controlled STEALTH C-1 trial to assess the safety and efficacy of nitazoxanide plus pegylated interferon, with or without ribavirin, in 120 patients with genotype 4 chronic hepatitis C at 2 centers in Egypt.
Participants were sequentially allocated into 3 treatment arms:
• 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day ribavirin for 48 weeks (standard of care) (n = 40 treatment-naive);
• 500 mg twice-daily nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus pegylated interferon for an additional 36 weeks (n = 28 treatment-naive + 12 treatment-experienced);
• Nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus both pegylated interferon and ribavirin for 36 weeks (n = 28 treatment-naive + 12 treatment-experienced).
The primary endpoint was sustained virological response (SVR), or HCV RNA <10 IU/mL 24 weeks after the end of treatment. Secondary endpoints included HCV RNA <10 IU/mL at week 4 (rapid virological response, or RVR), at week 12 (early virological response, EVR), and at the end-of-treatment (ETR).
Results
• Among the 96 treatment-naive patients, the SVR rate was 79% in the triple therapy arm, compared with 61% in the nitazoxanide-pegylated interferon dual therapy arm, and 50% in the standard-of-care arm (P = 0.023).
• Among the 24 treatment-experienced patients, the SVR rate was 25% in the triple therapy arm compared with 8% in the nitazoxanide-pegylated interferon arm.
• RVR, EVR, and ETR rates are shown in the table below (see next study description).
• Adverse events were generally similar across all 3 treatment arms.
• The exception was that the rate of anemia was significantly lower in the group that did not receive ribavirin.
Based on these findings, the investigators concluded, "The addition of nitazoxanide to pegylated interferon or pegylated interferon-ribavirin improved virologic response rates compared with pegylated interferon-ribavirin therapy without increase in adverse events."
4-week Lead-in
In a related poster, the investigators presented results from a study in which the lead-in nitazoxanide monotherapy phase was shortened to 4 rather 12 weeks.
In this study, 44 treatment-naive Egyptian patients (40 with genotype 4; 3 with genotype 1; 1 with genotype 2) received 500 mg twice-daily nitazoxanide for 4 weeks followed by nitazoxanide plus 180 mcg/week pegylated interferon for 36 weeks, without ribavirin. Sustained response rates at 12 weeks (SVR12) were reported.
Results
• 80% of patients treated with the 4-week lead-in dual therapy regimen achieved SVR12, compared with 50% in the standard-of-care arm of STEALTH C-1 (used as a historical control) (P = 0.004).
• RVR, EVR, and ETR rates for the 4-week lead-in, as well as the 12-week lead-in in STEALTH C-1, are shown in the table below.
• All the genotype 1 and 2 patients responded to the 4-week lead-in regimen.
• Adverse events were similar to those observed in STEALTH C-1.
• There were no serious adverse events or discontinuations due to adverse events.
The investigators concluded that, "The nitazoxanide lead-in phase used in the STEALTH C-1 trial can be reduced from 12 weeks to 4 weeks without compromising RVR, EVR, and ETR rates."
The results from these 2 studies "confirm earlier data suggesting synergistic activity between nitazoxanide and peginterferon in genotype 4 patients and provide a first look at sustained virologic response in a limited number of genotype 1 patients," Rossignol said in a press release issued by Romark. "These data also provide interesting insights into the mechanism of action of nitazoxanide and confirm previous findings related to its safety."
The second study, he added, "show that the nitazoxanide lead-in phase prior to standard of care treatment can be reduced from 12 to 4 weeks with no apparent impact on virologic response rates."
Resistance
Researchers also reported results from a laboratory study of the potential for development of resistance to nitazoxanide and its primary metabolite, tizoxanide. Huh-7 cells harboring HCV replicons were exposed to increasing concentrations of nitazoxanide and tizoxanide.
Based on their findings, they concluded that tizoxanide resistance can be generated in HCV replicon-containing cell lines, but that development of resistance to nitazoxanide or tizoxanide did not induce resistance to interferon or ribavirin. In fact, treatment of HCV replicon cells with tizoxanide heightened the antiviral effect of subsequent interferon treatment. They added that tizoxanide resistance is conferred by changes in the cell line, not by mutations in the HCV replicon.
Romark Institute For Medical Research, Tampa, FL; Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Palo Alto, CA; Department Of Gastroenterology and Hepatology, University of Tanta, Tanta, Egypt; Department of Hepatology, Gastroenterology and Infectious Diseases, University of Benha, Benha, Egypt; Department of Tropical Medicine and Infectious Diseases, University of Alexandria, Alexandria, Egypt; Department of Microbiology and Immunology, Georgetown University Medical Center, Washington, DC. |
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楼主: 闹心啊
发表于 2009-10-21 12:35
