Comparative Efficacy of Oral Nucleoside or Nucleotide Analog Monotherapy Used in Chronic Hepatitis <scp>B</scp>: A Mixed‐Treatment Comparison Meta‐analysis

Wiens, Astrid; Lenzi, Luana; Venson, Rafael; Correr, Cassyano Januário; Rotta, Inajara; Pedroso, Fiona L.; Pontarolo, Roberto

doi:10.1002/phar.1188

Cited by 22 publications

(16 citation statements)

References 22 publications

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“…This result is consistent with those from previous studies [47, 48]. The study by Wilens et al showed that tenofovir was the most effective in inducing HBeAg seroconversion; however, patients receiving combination treatment and who were resistant to drugs were included in that study possibly influencing the accuracy of the results [10]. Given the lack of head-to-head research, the clinical baseline characteristics (e.g., HBV DNA, ALT level, and age) for NA treatment in CHB patients may affect the relative efficacy of drugs.…”

Section: Discussionsupporting

confidence: 91%

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HBeAg Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Nucleos(t)ide Analog Treatment: A Systematic Review and Network Meta-Analysis

Xing

Cao

et al. 2017

PLoS ONE

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BackgroundHBeAg seroconversion is an important intermediate outcome in HBeAg-positive chronic hepatitis B (CHB) patients. This study aimed to compare the effect of nucleos(t)ide analogs (NAs) on HBeAg seroconversion in treating CHB with lamivudine, adefovir, telbivudine, entecavir, and tenofovir.MethodsNetwork meta-analysis of NA treatment-induced HBeAg seroconversion after 1–2 years of treatment was performed. In addition, NA treatment-induced HBeAg seroconversion after 3–5 years of treatment was systematically evaluated.ResultsA total of 31 articles were included in this study. Nine and five studies respectively reporting on 1- and 2-year treatment were included in our network meta-analysis. In addition, 6, 5, and 5 studies, respectively reporting on 3-, 4-, and 5-year treatment were included in our systematic evaluation. Telbivudine showed a significantly higher HBeAg seroconversion rate after a 1 year treatment period compared to the other NAs (odds ratio (OR) = 3.99, 95% CI 0.68–23.6). This was followed by tenofovir (OR = 3.36, 95% CI 0.70–16.75). Telbivudine also showed a higher seroconversion rate compared to the other NAs after a 2 year treatment period, (OR = 1.38, 95% CI 0.92–2.22). This was followed by entecavir (OR = 1.14, 95% CI 0.72–1.72). No significant difference was observed between spontaneous induction and long-term telbivudine treatment-induced HBeAg seroconversion. However, entecavir and tenofovir treatment-induced HBeAg seroconversions were significantly lower than spontaneous seroconversion.ConclusionLong-term treatment with potent anti-HBV drugs, especially tenofovir and entecavir, may reduce HBeAg seroconversion compared with spontaneous HBeAg seroconversion rate. Telbivudine treatment, whether short term or long term, is associated with higher HBeAg seroconversion compared with the other NAs. However, the high rates of drug resistance likely limit the application of telbivudine.

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Section: Discussionsupporting

confidence: 91%

“…The meta-analysis by Wiens et al . showed that tenofovir exerts the strongest inducing effect on HBeAg seroconversion after 1 year of treatment [10]. Moreover, no study has systematically evaluated the effect of long-term treatment on HBeAg seroconversion thus far.…”

Section: Introductionmentioning

confidence: 99%

HBeAg Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Nucleos(t)ide Analog Treatment: A Systematic Review and Network Meta-Analysis

Xing

Cao

et al. 2017

PLoS ONE

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“…Similar values were generated by two other research groups [51,52]. One other NMA has been recently published [53]. This analysis, however, contains a number of methodological flaws, the most notable being the pooling of data from HBeAg-positive and -negative individuals.…”

Section: Discussionsupporting

confidence: 52%

The importance of baseline viral load when assessing relative efficacy in treatment-naïve HBeAg-positive chronic hepatitis B: a systematic review and network meta-analysis

Mealing

Ghement²,

Hawkins

et al. 2014

Syst Rev

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BackgroundTo date no network meta-analysis (NMA) has accounted for baseline variations in viral load when assessing the relative efficacy of interventions for chronic hepatitis B (CHB). We undertook baseline-adjusted and unadjusted analyses using the same data to explore the impact of baseline viral load (BVL) on CHB treatment response.MethodsWe searched Embase, Medline, Medline in Process and the Cochrane CENTRAL databases for randomised clinical trials (RCTs) of monotherapy interventions at licensed doses for use in CHB. Search strategies comprised CHB disease and drug terms (a combination of controlled vocabulary and free text terms) and also a bespoke RCT filter.The NMA was undertaken in WinBUGs using fixed and random effects methods, using data obtained from a systematic review. Individual patient data (IPD) from an entecavir clinical trial were used to quantify the impact of different baseline characteristics (in particular undetectable viral load (UVL) at 1 year) on relative treatment effect. Study level mean baseline values from all identified studies were used. Results were generated for UVL and presented as relative risks (RRs) and 95% credible intervals (CrIs) using entecavir as reference treatment.ResultsOverall, for all eight relevant interventions we identified 3,000 abstracts. Following full text review a total of 35 (including the contents of six clinical study reports) met the inclusion critera; 19 were in hepatitis B e antigen (HBeAg)-positive patients and 14 of the 19 contained outcome information of relevance to the NMA.Entecavir and tenofovir studies had heterogeneous patient populations in terms of BVL (mean values 9.29 and 8.65 log10 copies/ml respectively). After adjusting UVL for BVL using an informative prior based on the IPD analysis, the difference between entecavir and tenofovir was not statistically significant (RR 1.27, 95% CrI 0.96 to 1.47 - fixed effects). A similar conclusion was found in all sensitivity analyses. Adjusted tenofovir results were more consistent with observed clinical trial response rates.ConclusionsThis study demonstrates the importance of adjusting for BVL when assessing the relative efficacy of CHB interventions in achieving UVL. This has implications for both clinical and economic decision making.

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“…De igual modo, la dispersión de los puntos incrementales de C-E en el plano cartesiano reafirma la mayor C-E del TDF. Otros estudios costo-efectividad del tratamiento de la HBV que comparan TDF y ETV coinciden con nuestro estudio en reportar al TDF como más costo-efectivo (20,21) .…”

Section: Discussionunclassified

Costo-efectividad de dos terapias antivirales para hepatitis B crónica en el Perú: entecavir y tenofovir

Bolaños-Díaz¹,

Tejada

Sanabria

et al. 2017

Rev Peru Med Exp Salud Publica

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Objetivos. Comparar en términos de costo-efectividad a entecavir (ETV) y tenofovir (TDF) en el tratamiento del virus de la hepatitis B (HBV) en hospitales públicos del Perú. Materiales y métodos. Estructuramos un modelo de Markov, definimos la efectividad en años de vida ajustados a calidad (AVAC). Incluimos los costos directos del tratamiento en soles desde la perspectiva del Ministerio de Salud del Perú. Calculamos la relación entre costo y efectividad incrementales (ICER). Realizamos análisis de sensibilidad determinístico y probabilístico, considerando un rango de disponibilidad de pago (WTP) desde uno hasta tres veces el producto bruto interno (PBI) per-cápita, y el beneficio monetario neto (BMN) o ICER en el caso del análisis de tornado. Resultados. El tratamiento con TDF es más efectivo y menos costoso que ETV. El ETV tuvo un costo por AVAC de S/ 4482, y de S/ 1526 para TDF. El TDF mantiene un BMN progresivamente mayor conforme aumenta la WTP. La tasa de descuento fue la única variable con efecto significativo en la incertidumbre del modelo. Conclusiones. El tratamiento con TDF es más costo-efectivo que ETV en hospitales públicos del Perú. Palabras clave: Hepatitis B, antiretrovirales, Economía médica. (fuente: DeCS BIREME). COST-EFFECTIVENESS OF TWO ANTIVIRAL THERAPIES FOR CHRONIC HEPATITIS B IN PERU: ENTECAVIR AND TENOFOVIR ABSTRACTObjetives. To compare in terms of cost-effectiveness to entecavir (ETV) and tenofovir (TDF) in the treatment of hepatitis B virus (HBV) in public hospitals in Peru. Materials and methods. We structured a Markov model. We define effectiveness adjusted life years for quality (QALY). We include the direct costs of treatment in soles from the perspective of the Ministry of Health of Peru. We estimate the relationship between cost and effectiveness ratios (ICER). We performed sensitivity analyzes considering a range of willingness to pay (WTP) from one to three times the Gross Domestic Product (GDP) per capita, and a tornado analysis regarding Monetary Net Profit (BMN) or ICER. Results. Treatment with TDF is more effective and less expensive than ETV. The ETV had a cost per QALY of PEN 4482, and PEN 1526 TDF. The PTO maintains a progressively larger with increasing WTP BMN. The discount rate was the only variable with a significant effect on model uncertainty. Conclusion: Treatment with TDF is more cost-effective than ETV in public hospitals in Peru. INTRODUCCIÓNEl virus de la hepatitis B (HBV) pertenece a la familia Hepadnaviridae (ortohepadnavirus), y puede ocasionar tanto enfermedad aguda como crónica. Existen diez genotipos (A-J) que difieren en un 8%, y múltiples subgenotipos que difieren en un 4%(1,2) . La transmisión es por vía sanguínea, mediante relaciones sexuales, por procedimientos médicos con material o productos contaminados y, en menor medida, por vía transplacentaria (3) .El diagnóstico se realiza mediante la detección del antígeno superficial (HbsAg), en los casos de infección aguda se detectará además inmunoglobulina M (Ig M) contra el antígeno del núcleo (HbcA...

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Comparative Efficacy of Oral Nucleoside or Nucleotide Analog Monotherapy Used in Chronic Hepatitis B: A Mixed‐Treatment Comparison Meta‐analysis

Abstract: Tenofovir has the highest probability of reducing HBV DNA, normalizing alanine aminotransferase levels and inducing HBeAg seroconversion after 1 year of treatment. An efficacy comparison of therapies is an important tool to guide clinicians in selecting the optimal treatment option.

Cited by 22 publications

References 22 publications

HBeAg Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Nucleos(t)ide Analog Treatment: A Systematic Review and Network Meta-Analysis

HBeAg Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Nucleos(t)ide Analog Treatment: A Systematic Review and Network Meta-Analysis

The importance of baseline viral load when assessing relative efficacy in treatment-naïve HBeAg-positive chronic hepatitis B: a systematic review and network meta-analysis

Costo-efectividad de dos terapias antivirales para hepatitis B crónica en el Perú: entecavir y tenofovir

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