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To the Editor:

With great interest, we read the recent meta-analysis published in HEPATOLOGY, which compared peginterferon (PEG-IFN) alpha 2a and PEG-IFN alpha 2b for treatment of chronic HCV infection.1 The results of this meta-analysis and the entire topic are still controversially discussed and methodologic concerns have been raised about the recent study.2, 3 Awad et al. conclude in their study, in contrast to the results of the largest, well-controlled single trial published in 2009,4 that according to their analysis of pooled data from eight studies, PEG-IFN alpha 2a is associated with significantly higher SVR rates than PEG-IFN alpha 2b.

Here, we present the treatment results of a large, retrospective unsponsored, single center study of a northern German cohort of HIV-negative patients with chronic HCV infection. We analyzed a total of 486 treatment-naïve, monoinfected patients with chronic hepatitis C (genotype 1-3) who were treated at the University of Hamburg after January 2002 until June 2008 with standard combination treatment regimen with either PEG-IFN alpha 2a (Group A) or PEG-IFN alpha 2b (Group B) for 48 weeks (genotype 1) or 24 weeks (genotypes 2 and 3) with weight adapted ribavirin doses of 800-1400 mg, respectively. There were no significant differences of the demographics or severity of the liver disease in the two groups with the exception of slightly higher baseline viral loads in group B (Table 1).

Table 1. Baseline Clinical and Virological Characteristics of the Cohort and Virological Response at the End of Treatment and Follow-Up by Intention-to-Treat Analysis
CharacteristicGroup A (PEG-IFN Alpha 2a + Ribavirin)Group B (PEG-IFN Alpha 2b + Ribavirin)P Value
  1. ns, not significant.

Patients, n304182 
Mean age (minimum/maximum)43 (15/76)41 (19/68)ns
Sex, male/female (%)182/122 (60/40)110/72 (60/40)ns
Liver biopsy, n (%)180 (59)103 (57)ns
Fibrosis F3-F4, n (%)33 (18)15 (15)ns
HCV RNA, mean (minimum/maximum)649,197 (308/13,154,000)1,342,536 (269/20,000,000)0.02
Alanine aminotransferase mean (minimum/maximum)104 (11/422)93 (7/906)ns
Genotype, n (%)   
 1147 (48)88 (48)ns
 240 (13)18 (10)ns
 3117 (38)76 (42)ns
Overall   
Rapid virologic response141/304 (46%)80/182 (44%)ns
Complete early virologic response111/304 (37%)72/182 (40%)ns
End-of-treatment response268/304 (88%)156/182 (86%)ns
SVR185/304 (60,9%)109/182 (59.9%)ns
Relapse31/304 (10%)18/182 (10%)ns
Nonresponse23/304 (8%)16/182 (9%)ns
Breakthrough3/304 (1%)4/182 (2%)ns
Lost to follow-up62/304 (20%)35/182 (19%)ns
SVR by genotype   
 179/147 (53.7%)47/88 (53.4%)ns
 229/40 (72.5%)13/18 (72.2%)ns
 377/117(65.8%)49/76 (64.5%)ns
Patients with side effects294/304 (97%)179/182 (98%)ns

Both groups received comparable ribavirin doses during the treatment period. Primary endpoint of the study was defined as sustained viral response (SVR) by intention to treat analysis. Overall, SVR rates were comparable for both regimens (group A: 185/304 [60.9%]/group B: 109/182 [59.9%] P = ns) (Table 1). There were also no differences detected for any of the genotypes (GT) 1 through 3 (GT1: 79/147 [53.7%] versus 47/88 [53.4%], GT2 29/40 [72.5%] versus 13/18 (72.2%), GT3 77/117 [65.8%] versus 49/76 [64.5%]). Notably, we neither observed any significant differences of the early virologic response rates, the relapse rates nor differences of the rate of side effects in either group (Table 1). We conclude that the efficacy and safety of standard combination treatment regimens for chronic hepatitis C infection with PEG-IFN alpha 2a versus PEG-IFN alpha 2b are comparable in real-life treatment settings in a large northern German university-based study center.

One issue that has not been addressed thoroughly in recent discussions is the difficult handling of the PEG-IFN alpha 2b syringes which might have simply lead to a lower exposure to the interferon because of faulty handling of the syringes in a subset of patients. We specifically addressed and trained the handling of the PEG-interferon alpha 2b syringe with the patients. Thus it is intriguing to speculate that one of the reasons for the relative high SVR rate and much lower drop-out rate of patients treated with PEG-interferon alpha 2b in our cohort than found in the study published by Ascione et al. and Witthoeft et al.5, 6 might be due to this training. In our view, it is time to end this “pseudo-debate”: it can only be reiterated that equally high SVR rates can be achieved using either PEG-IFN and many other factors like optimal dosing of ribavirin, individualized tailoring of the length of the therapy, patient counseling about the proper handling of the syringes and the importance of adherence,7 or treatment of the side-effects have a much greater impact on “real life” treatment outcome than the actual choice of the interferon.8

Acknowledgements

We thank the patients who participated in this study. This work was supported by the German Research Agency (SFB841). JSzW, AWL, SL, PB have received speaker's fees from Roche and Essex Pharma in the past.

References

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  • 1
    Awad T, Thorlund K, Hauser G, Stimac D, Mabrouk M, Gluud C. Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: systematic review of randomized trials. HEPATOLOGY; 51: 1176-1184.
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    Cremieux P. Methodological issues in a meta-analysis. HEPATOLOGY; 52: 395-396; author reply 396-397.
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    Kershenobich D, Munoz L, Male R, Gaytan J, Sanchez F. Proceed with caution: peginterferon alpha-2a versus peginterferon alfa-2b in chronic hepatitis C. A systematic review of randomized trials. HEPATOLOGY; 52: 2240-2241; author reply 2241-2242.
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    McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 2009; 361: 580-593.
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    Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG, Picciotto FP, et al. Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection. Gastroenterology; 138: 116-122.
  • 6
    Witthoeft T, Hueppe D, John C, Goelz J, Heyne R, Moeller B, Teuber G, et al. Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: the PRACTICE study. J Viral Hepat; 17: 459-468.
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    Lo Re V,3rd, Amorosa VK, Localio AR, O'Flynn R, Teal V, Dorey-Stein Z, Kostman JR, et al. Adherence to hepatitis C virus therapy and early virologic outcomes. Clin Infect Dis 2009; 48: 186-193.
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    Schulze Zur Wiesch J, Lohse AW. Results of the IDEAL trial: “Mirror, mirror on the wall-which's the fairest peg-interferon of them all?” HEPATOLOGY 2009; 50: 2034-2037.
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    Marcellin P, Forns X, Goeser T, Ferenci P, Nevens F, Carosi G, Drenth JP, et al. Telaprevir is effective given every 8 or 12 hours with ribavirin and peginterferon alfa-2a or -2b to patients with chronic hepatitis C. Gastroenterology Oct 26, 2010. [Epub ahead of print].

Julian Schulze zur Wiesch*, Neele Pudelski*, Lena Hoepner*, Michael Supplieth*, Peter Buggisch*, Ansgar W. Lohse*, Stefan Lüth*, * University Medical Center Hamburg–Eppendorf, Hamburg, Germany.