The results of this randomized pilot study suggest that a subgroup of patients could achieve a sufficiently high rate of SVR after only a 4-wk course of peg-IFN-α2a monotherapy. One of the most IFN-sensitive subgroups appears to include patients with genotype 2 and low viral load who exhibit VR after 1 wk of treatment.
Patients with genotype 2 or 3 are more sensitive to peg-IFN-α plus ribavirin treatment than those with genotype 1, and the current recommendation advocates a 24-wk treatment course, because more than 80% of the former group will attain SVR[3-5,7,11,27
]. Recently, several studies suggested that the treatment duration could be shortened from 24 to between 12 and 16 wk without adversely affecting outcome in patients with genotype 2 or 3 who achieve VR after 4 wk of treatment[6-8,11
]. In contrast, large trials indicated that shortening the treatment duration to 16 or 14 wk lessened the SVR rates[9,10
]. It remains controversial whether the optimal treatment duration is 24 wk or less than 24 wk for patients with genotype 2 or 3. A shorter treatment may not to be suitable for every patient with genotype 2 or 3. There may be a need to investigate whether the 4 wk timepoint from the beginning of treatment is appropriate to predict the therapy outcome after 24-wk treatment course.
There is ample evidence that peg-IFN-α plus ribavirin treatment is more beneficial in patients with genotype 2 than those with genotype 3[4,7-10
]. This suggests that treatment regimens should be tailored or individualized for each genotype, with a special emphasis on the duration of treatment. As for patients with genotype 2 alone, even high-dose conventional IFN-α monotherapy for 24 wk produced an SVR rate of 78%[14
]. Furthermore, the inclusion of baseline viral load and initial virologic response, as strong predictors of SVR independent of genotype[4,6,7,10,11,15,16,19-24,27
], may identify patients suitable for shorter treatment in a more accurate way. In a small size study, an SVR rate of 100% was reported in patients with genotype 2a and low viral load (< 100 KIU/mL) treated with IFN-α for 6 wk[28
]. In another study, 89.5% and 100% of patients, without genotype 1 and high viral load (> 100 KIU/mL), who showed VR after 2 wk of treatment, achieved SVR with 8-wk and 24-wk peg-IFN-α2a monotherapy, respectively[29
]. Although the sample size was very small, this pilot randomized trial suggested that the duration of peg-IFN-α2a monotherapy may be further shortened while maintaining a high SVR rate by dividing patients according to the presence or absence of strong predictors of response.
Common or characteristic adverse events are more severe and frequent in the combination treatment with ribavirin than in IFN-α or peg-IFN-α monotherapy, especially with prolonged treatment duration, leading to frequent withdrawals from treatment, because ribavirin accumulates in various tissues as well as in erythrocytes[2,15,24
]. Therefore, only a minority of patients in need of therapy actually receives peg-IFN-α plus ribavirin treatment. Before participation in this trial, IFN-based treatment has been withheld from some patients for a variety of reasons such as advanced age, or the relatively low hemoglobin level and/or platelet count. Symptoms recorded in this study were mild or few, supporting the view that a short treatment course is safer and associated with few adverse events and less frequent withdrawal from treatment[1,2,7,8,11,30
]. Our trial demonstrated that a 4-wk peg-IFN-α2a monotherapy was safe for such patients, and suggested that the indication for treatment could be extended to include patients considered otherwise unsuitable for the peg-IFN-α plus ribavirin combination therapy.
The combination treatment is costly, and the longer the treatment duration, the higher the cost of treatment. Currently, the cost of treatment of a person weighing 65 kg who receives peg-IFN-α2a at 180 μg weekly and ribavirin at 800 mg daily for 24 wk is approximately 11 253 USD in Japan. Thus, a 4-wk peg-IFN-α2a monotherapy would achieve a > 90% reduction in cost and drug exposure. When one adds the costs of medical consultation and laboratory tests, the 4-wk peg-IFN-α2a monotherapy provides a substantial saving in costs and inconvenience compared to the extended treatment.
In conclusion, the present study showed high SVR rates in genotype 2 patients with low viral load who had undetectable serum HCV RNA after 1 wk of treatment, treated with a 4-wk course of peg-IFN-α2a monotherapy. Tailoring or individualizing treatment to individual patients would considerably reduce both patients’ and society burdens, without adversely affecting the clinical outcome.