Treatment Options

Efficacy

The ultimate goal of treatment today is to achieve a sustained virological response (SVR). New data shows that >99% of these patients who achieved an SVR with PEGASYS® plus COPEGUS® remain HCV RNA negative throughout long term follow-up (5 years after achieving an SVR). The main predictors of response are HCV genotype and early on treatment viral response (RVR and EVR).

Efficacy data for genotype 1

Since the introduction of pegylated interferons we have seen a continuous increase in cure rates in trials. For G1 patients cure rates have increased to SVR rates up to 60% for combination treatment with PEGASYS® and COPEGUS®. This might be due to better handling of side effects by more experienced doctors therefore keeping more patients on treatment. However, still 40 to 50 percent of G1 patients fail to achieve this critical goal of therapy.

Figure 3-4: SVR rates in genotype 1

SVR rates in genotype 1

The new approach of Response-Guided Therapy allows physicians to adapt treatment according to on treatment viral response. With this new approach it is possible to preserve efficacy (up to 93% SVR) and to halve treatment duration (24 weeks) in G1 patients with a low viral load who achieve an RVR.

The licence for peginterferon alfa-2a now allows for a shorter 24-week course of treatment in patients with HCV genotype 1 with a low pre-treatment viral load (<800 000 IU/mL) and an undetectable viral load at week 4 and 24. (PEGASYS® EU SPC, revised 21/06/07, based on Jensen D, et al. Hepatology 2006; 43: 945-960 and Ferenci P, et al. 57th AASLD 2006; Abstract 390). This is the only indication of it’s kind in the EU.

Figure 3-5: 24 weeks' treatement it highly effective in G1 patients with an RVR

24 weeks' treatement it highly effective in G1 patients with an RVR

Efficacy data for genotype 2/3

Genotype 2/3 patients have a very high chance of achieving an SVR with only 24 weeks of therapy (up to 90%). Recent studies suggest that G 2/3 patients who achieve an RVR and have a low viral load achieve high rates of SVR even with a reduced treatment duration of 16 weeks (87% SVR).(Shiffman M, et al. N Engl J Med 2007;357:124-34)

However, for G 2/3 patients who do not achieve an RVR the chances to achieve an SVR is only 49%, and intensifying treatment might be an option for achieving higher rates of SVR. (Shiffman M, et al. N Engl J Med 2007;357:124-34)

Figure 3-6: SVR rates in genotype 2/3

SVR rates in genotype 2/3

Efficacy data for genotype 4

Recent data show that patients infected with genotype 4 benefit most from the more aggressive treatment regimen as recommended for genotype 1 infection, but can achieve SVRs more similar to those seen in patients infected with genotypes 2 and 3 (Diago et al, 2004).

Comparing treatment options

Clinical trials comparing PEGASYS® and COPEGUS® combination therapy with conventional IFNα-2b / RBV (RebetronTM)1 have shown that the PEGASYS® combination provides patients with significantly higher SVRs and is associated with an overall improved tolerability profile with less depression and fewer flu-like symptoms (Fried et al, 2002). There have been no large, prospective, head-to-head clinical trials directly comparing PEGASYS® and COPEGUS® with peginterferon alfa-2b (12KD) / RBV. However, a pilot study comparing the two treatments has been completed (Bruno et al, 2003). Response rates in difficult-to-treat genotype 1 patients indicated a trend towards the superiority of PEGASYS® and COPEGUS® over peginterferon alfa-2b (12KD) / RBV (SVR 46% vs 33%, respectively). (Bruno R, et al. Journal of Hepatology, Volume 41, Supplement 2, Sept 2004 , pp. 474-481.)

There have been a number of separate studies comparing PEGASYS® and COPEGUS® or peginterferon alfa-2b (12KD) / RBV with conventional IFNα-2b / RBV. PEGASYS® and COPEGUS® combination therapy was statistically significantly more effective than conventional IFNα-2b / RBV regardless of genotypes and baseline viral loads. In contrast, when tested in a population comprising patients infected with genotypes 1, 2 and 3, peginterferon alfa-2b (12KD) / RBV was only shown to be more effective in patients infected with genotype 1 and low viral load (Manns et al, 2001; PegIntron™ US Product Infomation, 2001).

A recent study funded by the U.S. Department of Veterans Affairs showed that patients receiving PEGASYS were 41% more likely to achieve an SVR than did patients receiving PegIntron (odds ratio 1.41, 95% confidence interval [CI] 1.18-1.69, P< .001) (Backus, et al, 2007).

Role of Ribavirin

Although RBV alone has no anti-HCV activity, when used in combination with IFNα it results in significant improvements in SVR, primarily by reducing relapse, although the precise mechanism for this action of RBV is still unclear.

It was shown that especially patients with G1 benefit from higher doses of ribavirin. This effect of ribavirin on SVR rates was shown for PEGASYS®  and for Peginterferon alpha 2b.

Figure 3-7: PEGASYS plus COPEGUS: increasing SVR rates in genotype 1

PEGASYS plus COPEGUS: increasing SVR rates in genotype 1

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