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Twice Weekly Higher Dosing of PegIntron Had Better Viral Response Rates in Genotype 1 Patients
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Reported by Jules Levin
Digestive Disease Week
May 15-20, 2004
New Orleans, LA.
"SUPERIOR EFFICACY OF TWICE A WEEK ADMINISTRATION OF PEGINTERFERON ALFA-2B PLUS RIBAVIRIN IN OBTAINING SVR IN HCV GENOTYPE 1"
Francesca Lodato (University of Bologna, Italy) reported these study results at the Digestive Disease Week Conference May 15-20 in New Orleans at an oral session yesterday May 16. This was an observational study and they examined twice weekly injections with a higher weekly dose of PegIntron compared to once weekly injection using a lower weekly dose. They found that twice weekly injections with the higher dose of PegIntron produced better viral response rates in genotype 1 patiens than the once weekly injections. But genotype 2 patients there was no difference in viral response rates as these easier to treat patients had similar rates of viral response with both dosing regimens.
Some difficult to treat patients achieve lower rates of sustained viral response (SVR) to interferon/RBV therapy for HCV. Lodato said in the program abstract that once a week administration of Peginterferon alfa-2b (Pegintron) produces an exponential decrease of serum drug's level being almost undetectable at days 6 and 7 after administration. PegIntron is dosed by once weekly subcutaneous injections as is Pegasys. The aim of this study is to evaluate whether twice a week administration may improve sustained virological response (SVR) in hepatitis C patients with negative baseline predictive factors. The study compares standard doses of PegIntron once a week to higher doses of PegIntron twice a week.
65 adult patients were consecutively enrolled: HCV RNA+ by PCR, elevated ALT, compensated liver disease. Exclusion criteria: HIV+, Child B, HBsAg+.
Patients were assigned to receive
--PegIntron 1.5 ug/kg once a week (Group A QW)
--PegIntron twice a week mean dose 2.5 ug/kg/week (group B BIW)
--both groups also received RBV 10.6 mg/kg/day
In group B, PegIntron was administeredon Mondays (1.5 ug/kg) and Fridays (1.0 ug/kg).
Quantiative HCV RNA: Versant HCV RNA 3.0 bDNA Bayer (range of quantification 650-7,700,000 IU/mL). Qualitative HCV RNA: Versant HCV RNA TMA Bayer (sensitivity of 5.3 IU/mL).
BASELINE PATIENT CHARACTERISTICS:
Groups were comparable for rate of naive, non responders and relapsers, for prevalence of genotype 1, for male/female ratio and for age of patients. Genotype 1 patients were treated for 48 weeks, genotype 2 for 24 weeks. The follow-up period was 24 weeks. Statistical differences between groups were calculated with chi-square test. 22 in group A (12 men/10 females); 43 in group B (23 men; 20 females). Mean age was 48-49 yrs. 23-21% had cirrhosis. Genotype 1-4 (N/NR/R): 6/6/3 (Group A); 9/12/5 (Group B). Baseline viral load: 6.11-6.12 log IU/mL. ALT: 48-49.
RESULTS
These results are only for genotype 1 patients. Genotype 2 patients all did well and had high response rates. After 4 weeks group B (twice weekly) had non-significantly better viral response (50% vs 26%, p=ns). After 12 weeks viral response was significantly (p=0.026) for group B (69% vs 33%). The End of treatment viral responses trended towards significance (p=0.055) and favored twice weekly administration (58% vs 27%).
Twice weekly administration showed better viral response rates among treatment-naives, relapsers, and nonresponders, but differences were not significant. When combining naives plus relapsers viral response rate was 57% for twice weekly vs 10% for once weekly and was significant (p=0.039).
Discontinuation rates were high: 46% for group A; 31% for group B (p=ns). Reductions in neutrophil counts were similar between groups A & B.
SIDE EFFECT PROFILE. flulike symptoms 53% in both groups; fatigue: 40% in group A vs 23% in group B. depression 13% in group A vs 7% in group B. weight loss: 0% in group A vs 11% in group B. irritability: 6-7% in both groups. Nausea & vomiting: 6% in group a & 0% in group B. psoriasis: 0% in group A vs 7% in group B. headache: 13% in group A vs 0% in group B.
The authors concluded that the present data from our observational study suggest that in patients with negative predictors of sustained response high doses of PegIntron twice weekly may increase the rate of sustained virologic response. In a non selected population of patients with chronic hepatitis C, twice a week administration of Pegintron is more effective than once a week administration in genotype 1 naive patients. Tolerability and adherence to treatment was higher for the twice a week group (B), probably because the twice a week administration is able to induce tachyphilaxis, producing a continuous drug exposure.
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