RESUMEN
Objective: To update the health economic evaluation of pirfenidone in the treatment of idiopathic pulmonary fibrosis (IPF) compared to all available alternatives strategies (Best supportive care - BSC and nintedanib), based on a cost-utility model previously validated by the CEESP's (French Committee for Economic Evaluation) in 2014. Methods: A standard Markov cohort model, adapted to French methodology guidelines, was used to simulate the therapeutic management and the course of IPF patients (including potential adverse events) using the collective perspective. Cost-effectiveness was evaluated regarding life years (LY); quality-adjusted life-years (QALY); average cumulative costs; the incremental cost-effectiveness ratio (ICER) expressed in cost per QALY gained. Data were retrieved from trials, meta-analysis, literature, health insurance and hospitalisation databases, and national tariffs. Results: Over 15 years, total costs accumulated in the pirfenidone strategy were estimated at 99,477 per patient, 104,610 in nintedanib, and 14,177 in Best Supportive Care (BSC). The total number of QALYs accumulated equalled 5.20 (6.91 LYs), 4.52 (5.98 LYs), and 3.79 (4.98 LYs), respectively. Pirfenidone was estimated to be dominant over nintedanib with incremental costs of -5,133 and 0.67 more QALYs accumulated. Incremental cost versus BSC was 85,300 and 1,404 QALY gained. The cost-effectiveness ratio was estimated at 60,738/QALY when compared to BSC. Conclusion: Pirfenidone is likely to be a cost-effective strategy compared to BSC and seems more efficient and less costly compared to nintedanib for the treatment of patients with IPF in France.
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The objective of the present study was to evaluate the virological efficacy of a 3-month short-course intensification with enfuvirtide (ENF) associated with an optimized background regimen (OBR) in treatment-experienced patients infected with HIV-1 with multiple therapeutic failures. This was a prospective, randomized, open-label multicenter trial including patients infected with HIV-1 and harboring a multi-resistant virus that was still susceptible to at least 2 active compounds. Patients were randomized (1:1) to receive OBR + ENF or OBR alone. ENF was discontinued at Week 12. The primary endpoint was the proportion of patients with plasma viral load <50 copies/ml at Week 24. Fifteen patients were randomized into the OBR group and 14 into the OBR + ENF group with a median viral load of 4.1 log(10) copies/ml and a median CD4+ cell count of 346 cells/mm(3) . The primary endpoint was achieved in 93% (14/15) and 79% (11/14) of patients, respectively. Eighty-seven percent (13/15) of patients had a viral load <50 copies/ml as soon as Week 12 in the OBR group and 79% (11/14) in the OBR + ENF group. At Week 12, the median CD4+ cell count was 327 in the OBR and 437 in the OBR + ENF groups and at Week 24 they were comparable. Intensification with ENF had no significant impact on PBMCs HIV-DNA levels. A 3-month short-course intensified treatment with ENF did not improve Week-24 virological response in treatment-experienced patients infected with HIV-1 harboring resistant viruses that were still susceptible to two antiretroviral drugs.
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Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Proteína gp41 de Envoltorio del VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Fragmentos de Péptidos/administración & dosificación , Terapia Recuperativa/métodos , Adulto , Anciano , Enfuvirtida , Femenino , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Carga ViralRESUMEN
BACKGROUND: The aim of this study was to document in real life the characteristics and management of hepatitis C patients treated with pegylated interferon-α2a and ribavirin, and the efficacy of treatment (sustained virological response [SVR]). METHODS: This observational study enrolled hepatitis C patients initiating pegylated interferon-α2a and ribavirin treatment. RESULTS: A total of 2,066 patients were included, of which 70% were treatment-naive, 53% had genotype (G) 1 and 38% G2 or G3 infection, and 35% had an F3-F4 Metavir score. In total, 18% of patients treated for 24 weeks and 39% of patients treated for 48 weeks prematurely stopped treatment, mainly because of side effects. The SVR rate (intent-to-treat population) was 39%: 43% in naive patients and 31% in treatment-failure patients. In the complete case analysis population, this was 49%: 54% in naive patients and 37% in treatment-failure patients. Among naive patients, the SVR rate was 42% in G1 carriers and 69% in G2 or G3 carriers. The SVR rate was 69% in naive G1 patients without fibrosis (F0; versus 44% in F1-F2 versus 31% in F3-F4; P<0.001). In naive patients, G2 or G3, low viral load (<800,000 IU/ml) and age ≤40 years were predictive factors for SVR. In treatment-failure patients, low viral load, no or low fibrosis stage (F0-F1) and no treatment modification were predictive factors of SVR. CONCLUSIONS: In patients treated in a real-life setting, adherence to therapy, SVR rates, predictive factors of SVR and safety results were close to those observed in randomized trials. A high SVR in G1 naive patients with no fibrosis warrants further study and might suggest earlier treatment.
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Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Factores de Edad , Antivirales/efectos adversos , Biomarcadores Farmacológicos/análisis , Estudios de Cohortes , Femenino , Francia , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Hepatitis C Crónica/patología , Hepatitis C Crónica/virología , Humanos , Interferón-alfa/efectos adversos , Masculino , Persona de Mediana Edad , Observación , Polietilenglicoles/efectos adversos , ARN Viral/biosíntesis , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Ribavirina/efectos adversos , Resultado del Tratamiento , Carga Viral/efectos de los fármacosRESUMEN
Ribavirin remains today a pivotal drug in the treatment of hepatitis C; in standard double therapy, as well as in triple combination with direct antiviral agents, ribavirin reduces relapse and can double the sustained virological response obtained with peginterferon alone or in association with direct antiviral agents. In the complex network of interacting factors determining sustained virological response independently of known predictive factors related to host and virus, two modern tools are emerging: polymorphisms in the IL28B gene and very early exposure to ribavirin. The use of a pharmacokinetic-pharmacodynamic model of early ribavirin exposure to adjust the dose individually would help promote a safer ribavirin use and improve sustained virological response. The variability of the influence of ribavirin exposure on anaemia is probably genetically determined; however, the low prevalence of the implicated protective alleles of the inosine triphosphate pyrophosphatase gene could explain their lack of influence on sustained virological response.
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Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Interleucinas/genética , Ribavirina/uso terapéutico , Anemia/inducido químicamente , Anemia/genética , Antivirales/efectos adversos , Antivirales/farmacocinética , Quimioterapia Combinada , Hepatitis C/genética , Humanos , Interferón alfa-2 , Interferón-alfa/uso terapéutico , Interferones , Polietilenglicoles/uso terapéutico , Pirofosfatasas/genética , Proteínas Recombinantes/uso terapéutico , Ribavirina/efectos adversos , Ribavirina/farmacocinética , Carga ViralRESUMEN
BACKGROUND: The efficacy of a maintenance therapy in non-responder patients with chronic hepatitis C has been essentially evaluated by histological semiquantitative scores. AIM: The aim was to evaluate the efficiency of 2 years of treatment with peginterferon alpha-2a vs alpha-tocopherol in these patients by histology, morphometry and blood markers of fibrosis. METHOD: Hundred and five HCV patients with a Metavir fibrosis score > or = 2 were randomized to receive peginterferon alpha-2a 180 microg/week (PEG) (n=55) or alpha-tocopherol (TOCO) 1000 mg/day (n=50) for 96 weeks. The primary endpoint was improvement or stabilization of the Metavir fibrosis score by biopsy performed at week 96. Secondary endpoints included a quantitative assessment of fibrosis by morphometry and changes in blood markers of fibrosis. RESULTS: There was no difference at baseline between PEG and TOCO according to the metavir (83.3 vs 86.8%, P=0.751) stage. The median fibrosis rate, measured with morphometry was 2.72 and 2.86% at day 0, and 3.66 and 2.82% at week 96, in the PEG and TOCO groups (P=0.90) respectively. However, the percentage of patients with metavir activity grade improvement was significantly higher in the PEG group vs the TOCO group (52.8 vs 23.7%, P=0.016). Non-invasive markers analysis did not show any significant change in both groups. CONCLUSION: Long-term therapy with peginterferon alpha-2a did not reduce liver fibrosis degree assessed by morphometry and blood tests as compared with alpha-tocopherol. Blood tests could be useful to assess liver fibrosis changes in clinical trials.