Health & Medical hepatitis

Clinical Impact of Treatment Timing for Chronic HCV

´╗┐Clinical Impact of Treatment Timing for Chronic HCV

Results


Immediate treatment with interferon-containing therapy, with the option of retreatment with interferon-free therapy for those do not initially attain SVR led to the greatest gains in quality-adjusted life expectancy (3.1 QALYs and 8.6 QALYs in noncirrhotic and cirrhotic patients, respectively, compared to no treatment). When retreatment was not an option, delayed treatment with interferon-free therapy was superior to immediate treatment with interferon-containing therapy by 0.2 QALY in noncirrhotic patients and 1.1 QALY in patients with cirrhosis (Table 2).

The superiority of delayed interferon-free therapy compared to one-time, immediate interferon-containing therapy was sensitive to the time that patients were forced to wait before receiving interferon-free treatment. In patients with and without cirrhosis, the health benefit of waiting for interferon-free therapy was lost when wait time for this regimen was greater than 3 years for patients with cirrhosis and 3.2 years for noncirrhotic patients (Fig. 3). Increasing delay in interferon-free therapy resulted in decreasing health benefits compared to no therapy, an effect that was greater in patients with cirrhosis compared to noncirrhotic patients.



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Figure 3.



Impact of increased wait time for delayed therapy. Immediate, interferon-containing therapy (solid lines) was compared to delayed, interferon-free therapy (dashed lines) for noncirrhotic (grey lines) and cirrhotic (black lines) patients as wait time for interferon-free therapy was increased. IFN, interferon; tx, treatment.





Base case results remained robust despite broad variation in age at start of the simulation (varied from 40 to 80 years old), mortality rate associated with HCV infection, quality of life with HCV infection and while on treatment and method for calculating joint health states. For example, interferon-free therapy at 1 year remained superior to one-time immediate interferon-containing therapy when the quality of life with cirrhosis and decompensated cirrhosis was equivalent to death (Table 2). When quality of life while receiving interferon was equivalent to death, waiting for interferon-free therapy remained superior to immediate one-time interferon-containing therapy. The superiority of waiting 1 year for interferon-free therapy persisted until the incidence of liver-related death reached 98 of 100 person-years (approximately 70 times the base case incidence) in noncirrhotic individuals and 12 of 100 person-years (approximately 9 times the base case incidence) in cirrhotic individuals (not shown). Two-way sensitivity analyses of the impact of age at start of simulation and wait time for interferon-free therapy are shown in Fig. 4.



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Figure 4.



Two-way sensitivity analysis of age and time to delayed therapy, noncirrhotic patients. Health benefits for (a) noncirrhotic patients and (b) patients with cirrhosis of immediate, interferon-containing therapy were compared to delayed, interferon-free therapy as patient age and wait time for interferon-free therapy were varied. Waiting for interferon-free therapy was favoured in the grey shaded area, whereas immediate, interferon-containing therapy was favoured in the un-shaded area. IFN, interferon.





In probabilistic sensitivity analysis, interferon-free therapy with 1-year delay was superior to one-time immediate interferon-containing therapy for patients without cirrhosis in 88.2% of one thousand cohorts of one thousand simulated patients. For patients with cirrhosis, the interferon-free therapy was superior in 95.4% of one thousand cohorts of one thousand simulated patients.

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