| |
PegIntron + Ribavirin in Coinfected Patiernts, RIBAVIC Study Results
|
| |
| |
JAMA PUBLISHES STUDY DEMONSTRATING PEGINTRON AND REBETOL ACHIEVED HIGHER SUSTAINED RESPONSE THAN STANDARD INTERFERON COMBINATION THERAPY IN PATIENTS COINFECTED WITH HEPATITIS C AND HIV
ANRS HC02 RIBAVIC STUDY HELPS ADDRESS MAJOR CHALLENGES IN TREATING COINFECTED PATIENTS
BRUSSELS, Belgium, Dec. 15, 2004 -- Patients coinfected with chronic hepatitis C virus (HCV) and HIV treated with PegIntron (peginterferon alfa-2b) and Rebetol (ribavirin) combination therapy achieved significantly higher rates of sustained virological response (SVR) compared to those treated with standard interferon combination therapy (interferon alfa-2b and ribavirin), according to results of the ANRS HC02 RIBAVIC study conducted by the Agence Nationale de Recherches sur le SIDA (ANRS) of France and published in this week's Journal of the American Medical Association (JAMA).1 SVR, defined as the sustained undetectability of HCV six months following the end of treatment, was the primary endpoint of the study.
These findings are important because complications of HCV infection are among the most frequent and difficult challenges in treating patients with HIV infection and AIDS (acquired immunodeficiency syndrome).2,3 HCV infection is the leading cause of morbidity and mortality in these patients.
"PegIntron and Rebetol combination therapy previously has been shown effective in treating a variety of hepatitis C patient populations, including patients with difficult-to-treat forms of the disease, and this large, well-controlled study shows this applies to coinfected patients as well," said Prof. Christian Perronne, M.D., Ph.D., Centre Hospitalier Universitaire Raymond Poincaré, Université de Versailles, Garches, and the ANRS study coordinator.
He noted that success in treating HCV/HIV coinfected patients greatly depends on a variety of factors, including the baseline disease characteristics of the patients. In the ANRS HC02 RIBAVIC study, approximately 40 percent of patients had advanced liver disease (cirrhosis or bridging fibrosis); 60 percent had HCV genotype 1 or 4, the most difficult types to treat; and 80 percent had used intravenous (IV) drugs.
"Our study included a high proportion of difficult-to-treat patients, including many with severe HIV- and/or HCV-related disease; and with characteristics associated with poorer treatment adherence, such as IV drug use and psychiatric disorders," Perronne said. "The fact that we included such patients and treated them in a 'real world' community setting makes our results relevant to the general population of patients living with HIV and HCV coinfection."
The ANRS HC02 RIBAVIC study is the fourth major study with pegylated interferon and ribavirin combination therapy in HIV/HCV coinfection to be published in the peer-reviewed literature. In these studies, overall SVR rates have ranged broadly (27 percent,1 27 percent,4 40 percent5 and 44 percent6), due in part to differences in baseline patient disease characteristics. However, in each of these studies, pegylated interferon and ribavirin has been shown to be more effective than standard interferon combination therapy in treating coinfected patients.
Study and Findings
The parallel-group, open-label trial involved 71 centers in France and 412 patients coinfected with HCV and HIV. Patients were randomly assigned to 48 weeks of treatment with either PegIntron 1.5 mcg/kg/week or Intron® A (interferon alfa-2b) 3 million units 3 times each week, both in combination with Rebetol 800 mg/day.
In the study, SVR was achieved in 27 percent of patients given PegIntron vs. 20 percent of those given Intron A (p=0.047). Importantly, among patients with difficult-to-treat genotypes 1 or 4, SVR rates also were significantly greater in the PegIntron group (17 percent vs. 6 percent, respectively, p=0.006). Results were similar among patients with genotypes 2, 3 or 5 (44 percent vs. 43 percent, respectively). SVR rates were higher among those who received at least 80 percent of the planned total dose of the treatments (40 percent vs. 29 percent, respectively). Responders showed significant improvement in scores related to severity of liver fibrosis and cirrhosis.
Treatment discontinuations for any reason occurred frequently in the study (39 percent) and in the same proportion in both treatment groups, perhaps reflective of the severe baseline disease characteristics of the patient population. It is noteworthy that no growth factors (neither granulocyte-colony stimulating factor nor erythropoietin) were used in this study to help maintain patients on therapy.
The two treatment regimens showed similar tolerability, although dose modifications for clinical adverse events and laboratory abnormalities were more frequent in the PegIntron group. The incidence of most adverse events was similar, with the most frequent being influenza-like symptoms (fatigue, fever, rigor, myalgia or headache).
The sponsor of the ANRS HC02 RIBAVIC study is the Agence Nationale de Recherches sur le SIDA (ANRS). Schering-Plough supplied the PegIntron, Intron A and Rebetol used in the study.
HCV/HIV Co-Infection
Peginterferon plus ribavirin combination therapy is the worldwide standard of care in the treatment of chronic hepatitis C virus infection, which affects more than 10 million people in major world countries, including five million in Europe. Coinfection with HCV and HIV is currently seen in about 33 percent of patients and as high as 90 percent in patients with a history of intravenous drug use. Liver disease caused by chronic hepatitis C virus infection is now a leading cause of morbidity and mortality among HIV-infected patients in the developed world, where classic opportunistic complications of severe immunodeficiency have declined dramatically as a result of the widespread use of highly active antiretroviral therapy. Thus, the adequate management of HCV-related chronic liver disease in HIV-infected patients arises as a major concern in this population.
PegIntron and Rebetol Combination Therapy
PegIntron and Rebetol combination therapy for chronic hepatitis C was approved in the European Union (EU) in March 2001. The recommended dose for combination therapy is PegIntron 1.5 mcg/kg/once weekly plus Rebetol 800-1,200 mg daily, adjusted to body weight. PegIntron had previously received centralized marketing authorization in the EU and is marketed as a monotherapy in cases of intolerance or contraindication to ribavirin for the treatment of adult patients with chronic hepatitis C.
PegIntron, recombinant interferon alfa-2b linked to a 12,000 dalton polyethylene glycol (PEG) molecule, is a once-weekly therapy dosed according to patient body weight that is designed to achieve an effective balance between antiviral activity and elimination half-life.
Rebetol is an oral formulation of ribavirin, a synthetic nucleoside analog with broad-spectrum antiviral activity. It is approved worldwide for use in combination with PegIntron or Intron A for the treatment of chronic hepatitis C.
Schering-Plough Corporation (NYSE: SGP) of Kenilworth, N.J., USA, is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 30,000 people around the world. The company's Web site is www.schering-plough.com.
# # #
Note to Editors:
PegIntron and Rebetol are licensed to Aesca in Austria, Essex Pharma in Germany and Essex Chemie in Switzerland.
References
1. Carrat F, Bani-Sadr F, Pol S, Rosenthal E, Lunel-Fabiani F, Benzekri A, Morand P, Goujard C, Pialoux G, Piroth L, Salmon-Ceron D, Degott C, Cacoub P, Perronne C for the ANRS HC02 RIBAVIC Study Team. Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients. A randomized controlled trial. JAMA. 2004 Dec 15;292(23): 2839-2848.
2. Bräu N. Update on chronic hepatitis C in HIV/HCV-coinfected patients: viral interactions and therapy. AIDS 2003;17:2279-90.
3. Soriano V, Sulkowski M, Bergin C, et al. Care of patients with chronic hepatitis C and HIV co-infection: recommendations from the HIV-HCV International Panel. AIDS 2002; 16:813-28.
4. Chung RT, Andersen J, Volberding P, Robbins GK, Liu T, Sherman KE, Peters MG, Koziel MJ, Bhan AK, Alston B, Colquhoun D, Nevin T, Harb G, van der Horst C; AIDS Clinical Trials Group A5071 Study. Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004 Jul 29;351(5):451-459.
5. Torriani FJ, Rodriguez-Torres M, Rockstroh JK, Lissen E, Gonzalez-Garcia J, Lazzarin A, Carosi G, Sasadeusz J, Katlama C, Montaner J, Sette H Jr, Passe S, De Pamphilis J, Duff F, Schrenk UM, Dieterich DT; APRICOT Study Group. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients. N Engl J Med. 2004 Jul 29;351(5):438-450.
6. Laguno M, Murillas J, Blanco JL, Martinez E, Miquel R, Sánchez-Tapiasb JM, Bargalloc X, García-Criadoc A, de Lazzarid E, Larrousse M, Leon A, Lonca M, Milinkovic A, Gatell JM, Mallolas J. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for treatment of HIV/HCV co-infected patients. AIDS Sept 3 2004;18(13):27-36.
|
|
| |
| |
|
|
|
