Response-guided peg-interferon plus ribavirin treatment duration in chronic hepatitis C: Meta-analyses of randomized, controlled trials and implications for the future

Abstract

Response-guided pegylated interferon (peg-IFN) plus ribavirin (P/R) therapy trials on genotype (G)1 and G2/G3 hepatitis C virus-infected patients provide contradictory results. We conducted meta-analyses of randomized, controlled trials to address (1) the benefit of a 72-week extended-duration therapy in G1-slow responders and (2) adequate shortened duration therapy in G1 and G2/G3-rapid responders. Seventeen trials were selected, including 624 G1 rapid responders, 570 G1 slow responders, and 2,062 G2/G3 rapid responders. Virologic outcomes and treatment discontinuation data were collected from published articles and by asking investigators. Pooled estimates of sustained virologic response (SVR), relapse, and dropouts were calculated using the random effects model, considering the variability of shortened duration, ribavirin dose, genotype, and baseline viral load. In G1 slow responders, a 72-week extended duration increased SVR (110.7%; 95% CI [confidence interval]: 14.4% to 1 17.1%), decreased relapse (212.3%; 95% CI: 225.4% to 0%), and did not significantly increase drop-out rates (14.5%; 95% CI: 20.6% to 1 9.6%). The benefit of extended duration was lower when using a weight-based ribavirin regimen (18.7%; 95% CI: 11.7% to 1 15.8%). In G1 rapid responders, a 24-week shortened duration decreased SVR (212.5%; 95% CI: 219.2% to 25.8%) and increased relapse rates (18.8%; 95% CI: 12.9% to 1 14.8%). Such differences were not significant in patients with baseline viral load <400,000 UL/mL (24.4%; 95% CI: 29.8% to 1 1%). In G2/G3 rapid responders, SVR was more common for standard 24-week duration than for shortened durations (14.1%; 95% CI: 10.1% to 1 8.5), but this benefit was not significant when ribavirin was weight-adjusted and the short duration was 16 weeks (21.7%; 95% CI: 26.1% to 1 2.7%) and for G2 patients (11.6%; 95% CI: 20.2% to 1 5.5%). Conclusion: Long durations of P/R therapy improve SVR, regardless of genotype. This effect is nonetheless negligible in rapid responders, with the most favorable conditions for SVR (G2, G1 with low viral load, and G3 with weight-adjusted ribavirin regimen). (HEPATOLOGY 2011;54:789-800) T he standard of care for chronic hepatitis C is the combination of peg-interferon plus ribavirin that leads to hepatitis C virus (HCV) eradication in 60% of cases, with variations depending on the characteristics of host and virus and, in particular, viral genotype. 1,2 Patients infected with genotype 1Abbreviations: 95% CI, 95% confidence interval; cEVR, complete early virologic response; G1, genotype 1; G2/G3, genotype 2 and 3; HCV, hepatitis C virus; IFN, Interferon; IL-28B, interleukin-28B; ITT, intention-to-treat method LVL, low viral load; PCR, polymerase chain reaction; peg-IFN, pegylated interferon; P/ R, peg-interferon plus ribavirin; RCTs, randomized, controlled clinical trials; RVR, rapid virologic response; SRs, slow responders; SVR, sustained virologic response.From the

Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa

“…53,54 In HCV-2/3 patients who achieved RVR after PEG-IFN α plus RBV therapy, a meta-analysis study indicated that treatment for 24 weeks achieved greater SVR rates than treatment for 12-16 weeks. 9 However, the overall SVR rates were similar in these patients if they received PEG-IFN α plus weight-based RBV therapy. Compared with HCV-3 patients, the beneficial effects of 24 weeks over 12-16 weeks of treatment were limited in HCV-2 patients.…”

“…9,77 In East Asian HCV-1 patients who achieved RVR, two independent studies indicated that the SVR rate for 24 weeks of PEG-IFN α-2a plus RBV therapy is similar to 48 weeks of combination therapy in HCV-1 patients with baseline viral load ,400,000 IU/mL (94%-96% vs 100%, respectively). 53,54 In contrast, patients who failed to achieve RVR or patients who achieved RVR but had high viral load (.400,000-800,000 IU/mL) should receive 48 weeks of therapy to secure the SVR rates.…”

“…[5][6][7] In addition, the introduction of response-guided therapy (RGT), where the optimized treatment duration is on the basis of early viral kinetics during the first 12 weeks of treatment, has further increased the SVR rate to 70%-75%. 8,9 Interestingly, the SVR rates of Asian patients with HCV genotype 1 (HCV-1) infection receiving PEG-IFN α plus RBV combination therapy are higher than those of Western HCV-1 patients. In contrast, the response rates between Asian and Western non-HCV-1 patients are comparable.…”

Custo-efetividade da inclusão dos respondedores virológicos lentos no tratamento da hepatite C na presença da coinfecção com o HIV

“…Esse fato foi atenuado pela evidência de que apesar de existir diferença na efetividade entre o tratamento padrão (48 semanas) e o tratamento estendido (72 semanas), o perfil de segurança é semelhante nos dois cursos de tratamento 28 .…”

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

“…Monitoring of viral loads during therapy has proven to be useful in individualized HCV therapy. Futility rules and responseguided therapy (RGT) based on in-treatment virologic responses at treatment weeks 4, 8, 12, and 24 could provide information for optimal treatment durations to avoid unnecessary therapy, maximize cost-effectiveness, and minimize adverse events with interferon-based therapy [162][163][164][165].…”