Table 2.
Selected landmark treatment studies regarding first-generation protease inhibitor therapy
| Study | Study design | Treatment | Key results | Major contribution |
|---|---|---|---|---|
| HCV RESPOND-2 Bacon et al. 2011 (ref.116) |
Randomized, multicentre, double-blind, placebo-controlled trial n = 403 treatment-experienced patients with chronic HCV GT1 infection — relapsers and partial responders — no null responders were included |
Three treatment arms: A: Peg-IFN–RBV for 48 weeks + placebo (weeks 4–48) |
A SVR rate: 21% |
Established triple therapy with Peg-IFN–RBV–boceprevir as the standard of care for treatment-experienced patients with GT1 infection Demonstrated that 36 weeks of treatment are sufficient in patients with undetectable HCV RNA at week 8 |
| B: Peg-IFN–RBV for 36–48 weeks (depending on HCV RNA result at week 8 detectable or undetectable) + boceprevir (weeks 4–36) | B SVR rate: 59%; in those with undetectable HCV RNA at week 8: 86% | |||
| C: Peg-IFN–RBV for 48 weeks + boceprevir (weeks 4–48) | C SVR rate: 66%; in those with undetectable HCV RNA at week 8: 88% | |||
| Substantially higher rates of anaemia in patients treated with boceprevir (41–46% versus 21%) | ||||
| SPRINT-2 Poordad et al. 2011 (ref.117) |
Randomized, multicentre, double-blind, placebo-controlled trial n = 1,097 treatment-naive patients with chronic HCV GT1 infection |
Three treatment arms: A: Peg-IFN–RBV for 48 weeks + placebo (weeks 4–48) |
A SVR rate: 38% |
Established triple therapy with Peg-IFN–RBV–boceprevir as the standard of care for treatment-naive patients with GT1 infection Demonstrated that treatment can be shortened to 28 weeks in almost half of the patients using response-guided therapy |
| B: Peg-IFN + RBV for 28–48 weeks (28 weeks in those with undetectable HCV RNA between weeks 8 and 24; extended RVR) + boceprevir (weeks 4–28) | B SVR rate: 63%; 44% qualified for shorter treatment duration | |||
| C: Peg-IFN–RBV for 48 weeks + boceprevir (weeks 4–48) | C SVR rate: 66% | |||
| ILLUMINATE Sherman et al. 2011 (ref.118) |
Randomized, multicentre, double-blind, placebo-controlled trial n = 540 treatment-naive patients with chronic HCV GT1 infection |
Peg-IFN–RBV–telaprevir for 12 weeks, followed by Peg-IFN–RBV for 12 weeks Patients with undetectable HCV RNA between weeks 4 and 12 (extended RVR) were randomized A: stop treatment after 24 weeks |
65% had an extended RVR | Demonstrated that triple therapy including telaprevir can be shortened to 24 weeks in more than half of treatment-naive patients using response-guided therapy |
| A SVR rate: 92% | ||||
| B: Peg-IFN–RBV for another 24 weeks | B SVR rate: 88% | |||
| ADVANCE Jacobson et al. 2011 (ref.119) |
Randomized, multicentre, double-blind, placebo-controlled trial n = 1,088 treatment-naive patients with chronic HCV GT1 infection |
Three treatment arms: A: Peg-IFN–RBV–telaprevir for 12 weeks, followed by Peg-IFN + RBV for 12 weeks (extended RVR) or 36 weeks (no extended RVR) |
A SVR rate: 75%; extended RVR: 58% |
Established triple therapy with Peg-IFN–RBV–telaprevir as the standard of care for treatment-naive patients with GT1 infection Demonstrated that treatment can be shortened to 24 weeks in more than half of treatment-naive patients Identified anaemia and rash as relevant adverse events attributable to telaprevir treatment |
| B: Peg-IFN–RBV for 12 weeks + telaprevir for weeks 0–8 and placebo for weeks 8–12, Peg-IFN–RBV for 12 weeks (extended RVR) or 36 weeks (no extended RVR) | B SVR rate: 69%; extended RVR: 57% | |||
| C: Peg-IFN–RBV + placebo for 12 weeks followed by Peg-IFN–RBV for 36 weeks | C SVR rate: 44% | |||
| Important adverse effects associated with telaprevir treatment were skin rash and anaemia | ||||
| REALIZE Zeuzem et al. 2011 (ref.120) |
Randomized, multicentre, double-blind, placebo-controlled trial n = 663 treatment-experienced patients with chronic HCV GT1 infection — relapsers, partial responders and null responders included |
Three treatment arms: A: Peg-IFN–RBV–telaprevir for 12 weeks followed by Peg-IFN–RBV + placebo for 4 weeks followed by Peg-IFN–RBV for 32 weeks |
SVR rates A: overall: 59% Relapsers: 83% Partial responders: 59% Null responders: 29% |
Established triple therapy with Peg-IFN–RBV–telaprevir as the standard of care for treatment-experienced patients with GT1 infection Demonstrated that treatment efficacy remains limited in previous null responders to IFNα Identified anaemia and rash as relevant adverse events attributable to telaprevir treatment |
| B: Peg-IFN–RBV + placebo for 4 weeks, followed by Peg-IFN–RBV–telaprevir for 12 weeks + telaprevir followed by Peg-IFN–RBV for 32 weeks |
SVR rates B: overall: 54% Relapsers: 88% Partial responders: 54% Null responders: 33% |
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| C: Peg-IFN–RBV + placebo for 16 weeks followed by Peg-IFN–RBV for 32 weeks |
SVR rates C: overall: 15% Relapsers: 24% Partial responders: 15% Null responders: 5% |
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| ANRS CO20-CUPIC study Hézode et al. 2013 (ref.131) |
Real-world, multicentre, prospective, observational study n = 497 patients with chronic HCV GT1 infection All patients had cirrhosis Safety and efficacy analysis at week 16 of treatment |
Triple therapy according to the prescribing information at the discretion of each investigator Telaprevir (n = 292) Boceprevir (n = 205) |
Incidence of serious adverse events: 40% Mortality: 1.2% Severe infections: 4.8% Severe anaemia: 4.6% High risk of death or severe complications in patients with albumin <36 g/l and platelet count <100,000/µl |
Raised some important concerns regarding the safety of triple therapy with first-generation PIs in patients with advanced liver disease |
HCV, hepatitis C virus; IFN, interferon-α; GT, genotype; Peg-IFN, pegylated interferon-α; PI, protease inhibitor; RBV, ribavirin; RVR, rapid virological response; SVR, sustained virological response.