Letters to the Editor

Peginterferon alfa-2b vs. peginterferon alfa-2a in the treatmentof hepatitis C, is there any difference?

To the Editor:

In their recent article, Silva et al. [1] intended to‘‘determine if in vitro differences between peginterferonalfa-2b and peginterferon alfa-2a would translate to ob-servable differences in their in vivo biological activity,assessing the effect of treatment on early virologic re-sponse as well as expression of interferon response genesas markers of their mechanism of action’’. To do that;their purpose was to (relying on the sample size calcula-tion that they performed) ‘‘detect a difference in meansof log viral change of 1.65 (the difference between agroup who received peginterferon alfa-2b mean of�3.65 and a group who received peginterferon alfa-2amean of �2.00) at week 8’’. However, the questionremains as to what viral load patients have at week 8.The mean reduction in HCV-RNA in a group thatreceived peginterferon alfa-2b was 3.13 log10 (less thanthey expected!) and 2.44 log10 in patients treated withpeginterferon alfa 2a (more than they expected!) andof course the difference was hardly 0.69, far less thanthey expected (really only 40% of what they anticipated).Sadly, the authors did not state the standard deviationof the data and therefore it is not possible to tease outif the difference was statistically significant or not. Nev-ertheless, in order to show a competitive advantage infavor of peginterferon alfa 2b the authors focused onthe rate of decline in HCV-RNA during the 8 weeksof treatment. They found that there was a statistical dif-ference in favor of the group who received peginterferonalfa 2b with a P < 0.002, but is this difference clinicallyimportant? If it is, why didn’t they make a sample sizecalculation about this outcome variable? Digging into

the data, we can see that this statistically ‘‘significant’’difference lacks clinical importance with a simplearithmetic calculation. If we deduct from the inferiorlimit of the confidence interval of the group whoreceived peginterferon alfa-2b (0.29), the superior limitof the confidence interval of the group who receivedpeginterferon alfa-2a (0.28) we have 0.01! Would a dif-ference of 0.01 in the rate of decline in HCV-RNAduring 8 weeks of treatment in favor of peginterferonalfa-2b be clinically important? In my opinion, probablynot.

My last concern is about the Ethical Committees ofthe institutions where the study was carried out, whydid they allow (relying on the present evidence) peopleinfected with HCV genotype 1 to receive onlymonotherapy in their first 4 weeks of treatment?

Reference

[1] Silva M, Poo J, Wagner F, et al. A randomised trial to compare thepharmacokinetic, pharmacodynamic, and antiviral effects of pegin-terferon alfa-2b and peginterferon alfa-2a in patients with chronichepatitis C (COMPARE). J Hepatol 2006;45:204–213.

Fernando SierraDivision of Gastroenterology and Hepatology,

Fundacion Santa Fe and Los Andes University,

Bogota, Colombia

E-mail address: Fersi17@yahoo.com

doi: 10.1016/j.jhep.2006.11.004

Reply to Dr. Sierra’s letter on COMPARE study

To the Editor:I read with interest the comments by Dr Sierra

regarding the design and results of our recent

COMPARE study [1]. Dr Sierra accurately points outthat the predicted decline in hepatitis C virus (HCV)RNA for each treatment group was different from the

doi:10.1016/j.jhep.2006.11.004

www.elsevier.com/locate/jhep

Journal of Hepatology 46 (2007) 349–351