Cancer Treatment Today » Hepatitis

Procrit for anemia of Hepatitis C treatment – pro

M Levin, MD — Thu, 30 Aug 2012 02:08:51 +0000

Procrit is appropriate in the anemias due to erytrhopoietin underproduction or deficiency. In Hepatitis C it is usually both as well as due to chronic illness.

Several studies have evaluated the use of recombinant human erythropoietin alfa (rHuEPO) (Procrit and Epogen) for the treatment of ribavirin/interferon-induced anemia in HCV-infected patients. In a letter to the editor of Hepatology, researchers in France reported the results of a study of 13 patients with HCV, one of whom was also HIV-infected, who developed anemia on interferon alfa-2b/ribavirin treatment and who were treated with rHuEPO.

In one of the first studies, 9 patients received high dose (6 million units 3 times a week) and 3 patients low-dose (3 million units 3 times a week) interferon alfa-2b and 1 patient received PEG-interferon alfa-2b at 80 µg per week. Ribavirin was given at 1 gram or 1.2 gram per day. When anemia developed, rHuEPO was given at a dose of 4,000 units 2 to 3 times weekly to 11 patients, 8,000 units 3 times weekly to 1 patient, and 10,000 units 3 times weekly to 2 patients.

The baseline median hemoglobin in the 13 patients was 13.3 g/dL and the median hemoglobin nadir on interferon/ribavirin was 10.2 g/dL. On rHuEPO, the hemoglobin increased to a median of 11.5 g/dL and none of the patients on rHuEPO stopped treatment due to anemia. It should be noted, however, that the ribavirin dose was also decreased to 800 mg in 3 patients, to 600 mg in 1 patient, and to 200 mg in 1 patient (who had cirrhosis and HIV). The authors reported that 10 patients had an initial response to interferon/ribavirin treatment, with 4 achieving a sustained response, 5 still under treatment or follow-up, and 1 patient relapsed.

The authors conclude, “in our cohort of patients with chronic hepatitis C treated with interferon/ribavirin combination therapy, rHuEPO was beneficial in the treatment of ribavirin-induced anemia and allowed for the maintenance of a generally efficient ribavirin dosage. “Well-designed clinical trials with larger numbers of patients would be useful to establish the benefit of rHuEPO in this clinical situation as well as the optimal dose and frequency of administration.” This report supports the use of rHuEPO in patients with interferon/ribavirin induced anemia. Further studies are underway to evaluate the questions raised by the authors in their conclusion.

A recent study examined the relationship between ribavirin administration and endogenous erythropoietin production. Adequate endogenous erythropoietin production was demonstrated in patients with compensated liver disease in response to ribavirin-induced hemolytic anemia. The response was maintained, although the anemia was not corrected because of ongoing hemolysis and the continuous intake of ribavirin. The authors challenged the 40,000-U/week subcutaneous dosage administered in clinical trials because it was 3 times higher than the physiologic increase in erythropoietin production in response to ribavirin-induced anemia.

In a study of 46 patients with HCV infection, monotherapy with standard or peginterferon caused hemoglobin levels to decline below baseline values in 7 days, with a compensatory 70-96% increase in endogenous erythropoietin levels.] Reticulocyte production did not increase over baseline values; this finding represented an inadequate response to increased erythropoietin level and contributed to the development of anemia. Therefore, despite increased erythropoietin levels, the compensatory response could not overcome the suppressive effects of interferon alfa on bone marrow.This suggests that erytrhopoietin is not useful in this situation. It remains investigational and more and larger studies remain to be done.

Samit Hirawat, Stuart M. Lichtman, Steven L. Allen : Recombinant human erythropoietin use in hemolytic anemia due to prosthetic heart valves: A promising treatment American Journal of Hematology: 66, 3, 224-226, 2001

A. Gergely and others. Treatment of ribavirin/interferon-induced anemia with erythropoietin in patients with hepatitis C. Hepatology 2002; 35:1281.

Dev A, Patel K, Muir A, McHutchison JG. Erythropoietin for ribavirin-induced anemia in hepatitis C: more answers but many more questions. Am J Gastroenterol 2003;98(11): 2344-7.

Durante Mangoni E, Marrone A, Saviano D, et al. Normal erythropoietin response in chronic hepatitis C patients with ribavirin-induced anaemia. Antivir Ther 2003;8(1):57-63.

Peck-Radosavljevic M, Wichlas M, Homoncik-Kraml M, et al. Rapid suppression of hematopoiesis by standard or pegylated interferon-alpha. Gastroenterology 2002;123(1):141-51.

Ortho Biotech Products, L.P. Procrit (epoetin alfa) full prescribing information. Raritan, NJ; 2004.

Neupogen to allow ribavirin and interferon treatment of Hepatitits C – pro

M Levin, MD — Thu, 23 Aug 2012 15:16:07 +0000

Therapy with interferons have been associated with a greater decrease in absolute neutrophil counts than standard interferons, requiring dose reduction secondary to neutropenia in 18-20% of treated patients. While neutropeniais common, rarely is the neutropenia severe enough to warrant permanent discontinuationof therapy. If the neutrophil count drops below0.75 x 109 / L, the pegylated interferon doseshould be reduced by 50%. If the neutrophil count falls below 0.50 x 109 / L, therapy shouldbe discontinued. Neutrophil counts usuallyreturn to pretreatment levels within four weeksof stopping therapy. Based upon the concern ofneutropenia, many physicians have advocatedthe use of granulocyte-colony stimulating factor(G-CSF) at a dose of up to 300 ug subcutaneouslyper week. Currently, there are no clinical trials to demonstrate the effectiveness of G-CSF although clinical experience does support its efficacy in certain situations. Guidelines state: “Routine use of growth factors, such as epoetin and granulocyte colony-stimulating factor (G-CSF) was considered but not recommended”. At this time there is an absence of data supporting the preemptive use of growth factors in this patient population.

In most cases, the use is not routine but in order to enable therapy for hepatitis C.Many patients with chronic hepatitis C (HCV) infection undergoing treatment with pegylated interferon-alpha (PEG-IFN-alpha) and ribavirin develop neutropenia requiring dose reduction or granulocyte colony-stimulating factor (G-CSF) supplement. The VA wrote guidelines supporting its use under some conditions, but leukopenia has to be demonstrated first on interferon/ribavirin and dose reduction is to be pursued before Meupogen is used. In a recent database of patients who completed treatment for chronic HCV infection between 2003 and 2006, patients with absolute neutrophil counts below 1000 cells/microL were initiated on G-CSF (G-CSF group) while a matching group of patients who received anti-HCV treatment without developing neutropenia were used as a control group (non-G-CSF group). Patients on the G-CSF arm were divided into two subgroups based on the timing of G-CSF administration relative to PEG-IFN-alpha administration. Of the 163 patients with HCV infection, 30 patients received G-CSF, most of who were maintained on 300 microg of G-CSF once a week. Administration of G-CSF 2 days before or after each dose of PEG-IFN-alpha did not make a significant difference in the neutrophil counts. In the G-CSF arm, 23 of 30 patients (77%) had undetectable end-of-treatment viral response which was comparable with 27 of 30 in the control group (90%; P = 0.17). There was no statistically significant difference in the sustained viral response between the two groups (61%vs 76%, P = 0.18). In most patients PEG-IFN-alpha induced neutropenia improved with a once-a-week dose of G-CSF with a comparable virological outcome. Timing of G-CSF administration did not make any significant impact on the patient’s neutrophil counts but was better tolerated when given 2 days apart from PEG-IFN-alpha. Similar findings were reported by Lodato et a;.

A 2007 study from Georgia (Shavradze et al) concluded:” In patients with PEG-IFN/RBV therapy Neupogen effectively manages neutropenia and gives opportunity to maintain interferon dose (without reduction). Neupogen has the potential to improve adherence rates, which may in turn improve SVR.” The Authors reiterated this position in a 2009 editorial in a Georgian Medical News publication.In the USA, A 2005 TEC Assessment said this: “Well-designed RCTs show that patients treated with pegylated interferon, both as dual therapy and as monotherapy, experience higher sustained viral response rates than those treated with non-pegylated interferon. Patients with genotypes 2 and 3 experience the highest response, with rates in excess of 80%. Patients with the harder to treat genotype 1 nevertheless benefit, with up to 46% of patients experiencing an SVR in one of the trials. Pegylated interferon also appears to be relatively cost-effective in both monotherapy and dual therapy, with cost per QALY estimates remaining generally under 30,000 pounds sterling. The most favourable estimates were for patients with genotypes 2 and 3. Pegylated interferon is a relatively new intervention in the treatment of hepatitis C and therefore there are areas where further research is needed. These include: efficacies of therapy with PEG-alpha-2a vs PEG-alpha-2b; retreatment of previous non-responders using pegylated interferon; efficacy of treatments and long-term outcomes in patients who have other co-morbidities; prospective tests of rules governing stopping treatment; treating patients with acute hepatitis C; problems that may occur in a minority of patients with hepatitis C, such as cryoglobulinaemia and vasculitis; additional psychological effects on quality of life due to hepatitis C and also on the treatment of children and adolescents with hepatitis C.” On the balance, I read it as recommending Neupogen.

1. FILGRASTIM
DRUGDEX® Evaluations
Last Modified: February 08, 2012

2.Lodato F, Azzaroli F, Tame MR, Di Girolamo M, Buonfiglioli F, Mazzella N, Cecinato P, Roda E, Mazzella G.G-CSF in Peg-IFN induced neutropenia in liver transplanted patients with HCV recurrence.
World J Gastroenterol 2009 November;15(43):5449-5454

3.NY State Gudielines for Hep. C. - http://www.health.state.ny.us/diseases/communicable/hepatitis/guidelines/appena.htm

4.http://www.pbm.va.gov/criteria/GSCFCriteriaForUseforHepatitisC.pdf

5.Koirala J, Gandotra SD, Rao S, Sangwan G, Mushtaq A, Htwe TH, Adamski A, Blessman D, Khardori NM. Granulocyte colony-stimulating factor dosing in pegylated interferon alpha-induced neutropenia and its impact on outcome of anti-HCV therapy.J Viral Hepat. 2007 Nov;14(11):782-7.

Duration of treatment for Hepatitis C – pro

M Levin, MD — Fri, 22 Jun 2012 21:36:08 +0000

Lay Summary: Duration of treatment of Hepatitis C with interferon or interferon/ribavirin is usually 24 weeks and generally not tought to be beneficial beyond 48 weeks. Please consult the references for more specific recommendations.

Stephanos J. Hadziyannis, Hoel Sette, Jr., Timothy R. Morgan, Vijayan Balan, Moises Diago, Patrick Marcellin, Giuliano Ramadori, Henry Bodenheimer, Jr., David Bernstein, Mario Rizzetto, Stefan Zeuzem, Paul J. Pockros, Amy Lin, Andrew M. Ackrill, AND for the PEGASYS International Study Group Peginterferon-2a and Ribavirin Combination Therapy in Chronic Hepatitis C
A Randomized Study of Treatment Duration and Ribavirin Dose Annals 2004 140: 346-355

B. R. Schackman, P. A. Teixeira, G. Weitzman, A. I. Mushlin, and I. M. Jacobson
Quality-of-Life Tradeoffs for Hepatitis C Treatment: Do Patients and Providers Agree?
Med Decis Making, April 1, 2008; 28(2): 233 – 242.

J S Cross, C G Antoniades, and P M Harrison
Current and future management of chronic hepatitis C infection
Postgrad. Med. J., April 1, 2008; 84(990): 172 – 176.

Gerlach T, Buggisch P, Goeser T, Rasenack J, Pape GR, Schmidt WE, Kallinowski B, Klinker H, Spengler U, Martus P, Alshuth U, Zeuzem S. et al, Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin.Gastroenterology. 2006 Apr;130(4):1086-97.