2种用药方案治疗慢性丙型肝炎的药物经济学评价

目的:评价2种用药方案治疗慢性丙型肝炎(CHC)的经济学效果。方法:185例CHC患者按照治疗方案的不同分为长效组(聚乙二醇干扰素α-2a联合利巴韦林)与普通组(普通干扰素α-2a联合利巴韦林),针对不同基因型分别采用最小成本分析法和成本-效果分析法进行研究,效果指标采用持续病毒学应答率(SVR),成本指标采用直接医疗服务成本。结果:对于基因2型、3型的CHC患者,长效组与普通组的SVR分别为76.5%、63.5%(P>0.05),治疗成本分别为30235.20、36950.40元(P<0.05);对于基因1型、未分型的CHC患者,长效组与普通组的SVR分别为52.9%、25.8%(P<0.05),成本-效果比分别为114310.77、143218.60,长效组相对于普通组的增量成本-效果比为86789.67。结论:从药物经济学角度看,聚乙二醇干扰素α-2a联合利巴韦林治疗CHC优于普通干扰素α-2a联合利巴韦林方案。     

聚乙二醇干扰素α-2a＋利巴韦林

聚乙二醇干扰素α-2a＋利巴韦林对于HCV单独感染以及慢性HCV／HBV双重感染的患者同样有效。利巴韦林和聚乙二醇干扰素联合治疗是HCV单独感染的标准治疗方案。本研究评价了这种联合方案对HBV和HCV（1型、2型或3型）双重感染患者的疗效。     

2011年上半年美国FDA批准新药（续）

（续上期） 5.2波塞瑞韦胶囊 由Merck公司开发,2011年5月13日获得FDA批准,用于联合聚乙二醇化α-干扰素（peginterferon alfa）和利巴韦林（ribavirin）方案治疗≥18岁成人无既往治疗史或已经既往α-干扰素（interferon alfa）和利巴韦林方案治疗失败的呈代偿性肝病、包括已伴肝硬化的基因型为1的慢性丙型肝炎（CHC）患者。     

聚乙二醇干扰素α-2α与利巴韦林联合胸腺肽α1治疗慢性丙型肝炎疗效观察

自从聚乙二醇干扰素（PEG—IFN）α联合利巴韦林（RBV）应用于慢性丙型肝炎的治疗,并且基因2型或3型感染者可获得50％的持续病毒学应答（SVR）以来,PEG—IFNα联合RBV已经成为慢性丙型肝炎的标准治疗方案。但是,仍然有部分患者在标准治疗方案下,未能获得SVR。本研究应用PEG—IFNα-2α与RBV联合胸腺肽α1治疗慢性丙型肝炎,观察其疗效。     

不同干扰素与利巴韦林联用治疗慢性丙型肝炎的疗效评价

目的：评价不同种类干扰素与利巴韦林联用治疗慢性丙型肝炎（CHC）的疗效,为CHC患者抗病毒治疗方案的选择提供依据。方法：将96例CHC初治患者随机分成治疗组（50例）和对照组（46例）;治疗组患者予聚乙二醇干扰素α-2b,对照组患者（46例）予国产重组人干扰素α-2b,两组患者均予利巴韦林联用治疗;疗程结束后随访24周,评价两组患者病毒学应答情况。结果：经治疗和测试,治疗组基因Ⅰ型患者为32例,其快速病毒学应答率（RVR）、早期病毒学应答率（EVR）、治疗终点病毒学应答率（ETVR）和持续病毒学应答率（SVR）显著高于对照组（29例）,两组资料经比较其差异有统计学意义（P〈0.05）;治疗组非基因Ⅰ型患者为18例,其RVR、EVR、ETVR和SVR略高于对照组（17例）,经比较其差异无统计学意义（P〉0.05）。结论：对于基因Ⅰ型CHC患者,治疗组患者经治疗后,其SVR显著优于对照组,而对于非基因Ⅰ型CHC患者予国产重组人干扰素α-2b与利巴韦林联用治疗,更符合我国国情。     

聚乙二醇干扰素α-2a 联合利巴韦林治疗慢性丙型病毒性肝炎的疗效

目的：探讨聚乙二醇干扰素α-2a 联合利巴韦林治疗慢性丙型病毒性肝炎的疗效。方法选取2012年6月—2014年2月中牟县卫生防疫站收治的慢性丙型病毒性肝炎患者66例,随机分为研究组与对照组,各33例。研究组患者予以聚乙二醇干扰素α-2a 联合利巴韦林治疗,对照组患者予以重组人干扰素α-2b 联合利巴韦林治疗。观察两组患者血清学指标、丙氨酸氨基转移酶（ALT）复常与血清 HCV-RNA 阴转情况及不良反应发生情况。结果研究组患者早期病毒学应答（ EVR）、结束时病毒学应答（ ETVR）、持续病毒学应答（ SVR）率高于对照组（ P ＜0.05）;研究组患者 ALT 复常与 HCV-RNA 阴转率高于对照组（P ＜0.05）;两组患者均未发生严重不良反应。结论聚乙二醇干扰素α-2a 联合利巴韦林治疗慢性丙型病毒性肝炎的疗效显著,不良反应少,安全性高。     

美国FDA批准丙肝治疗新药波普瑞韦

美国FDA于2011年5月批准美国默克公司的慢性丙型肝炎治疗新药波普瑞韦（Boceprevir,商品名Victrelis）上市。波普瑞韦获准与长效干扰素聚乙二醇干扰素a和利巴韦林联用治疗CHC基因I型慢性丙肝感染,适用于患有代偿性肝脏疾病（包括肝硬化）的18岁及以上的成年患者,这些患者以前未经治疗或之前用干扰素和利巴韦林治疗失败。     

聚乙二醇α2b干扰素联合利巴韦林治疗基因1型HCV感染

美国Ordway研究所Drusano等采用建立评价模型的方法，对基因1型丙型肝炎病毒（HCV）感染者经聚乙二醇α2b干扰素（PEG-IFN α2b）和利巴韦林联合治疗48周的疗程长短以及疗程与停止治疗后持续病毒应答（SVR）的关系进行了研究。     

2013年版欧洲肝脏研究学会(EASL)丙型肝炎病毒感染管理临床实践指南解读

目的:两种蛋白酶抑制剂治疗基因1型丙型肝炎病毒(HCV)感染患者的Ⅲ期临床试验已经完成,并且在欧美等地区批准上市。欧洲肝脏研究学会(EASL)于2013年对HCV感染管理指南进行了修订更新。本文旨在对2013年版EASL丙型肝炎病毒感染管理临床实践指南进行部分解读。方法:从HCV治疗目标及终点、治疗适应证、不同基因分型HCV患者的治疗策略角度进行解读。结果与结论:聚乙二醇干扰素/利巴韦林(PegIFN/RBV)联合特拉泼维(TVR)或波赛泼维(BOC)是所批准的对基因1型HCV患者的标准治疗,PegIFN/RBV二联疗法仍然是非基因1型HCV患者的标准治疗。     

长效干扰素联合利巴韦林治疗慢性丙肝临床观察

目的 观察长效干扰素聚乙二醇干扰素(PEG-IFN)α-2a与普通干扰素(IFN)α-1b治疗慢性丙型肝炎(CHC)的临床疗效及安全性.方法 60例CHC患者分别采用PEG-IFNα-2a和IFNα-1b联合应用利巴韦林治疗,疗程48周,24周后随访.观察两组在病毒学应答和生化学应答以及药物不良反应方面的差异.结果 长...     

聚乙二醇干扰素α-2a联合利巴韦林对丙型肝炎肝硬化患者抗病毒治疗的疗效观察

目的观察聚乙二醇干扰素(Peg-IFN)α-2a联合利巴韦林对丙型肝炎肝硬化合并脾功能亢进患者在脾切除或部分脾栓塞术后抗病毒治疗的疗效。方法将31例丙型肝炎肝硬化(基因Ⅰ型HCV感染)合并脾功能亢进而未作抗病毒治疗的患者,在行脾切除术或部分脾栓塞术,脾功能亢进改善2个月后,给予Peg-IFNα-2a 135μg或180μg皮下注射,每周1次,联合利巴韦林800~1200mg/d治疗,疗程48周。治疗期间,第1、2、4、6、8、12周随访,之后每4周随访1次,停药后继续观察24周。治疗及随访期间观察肝功能、血常规、肾功能、HCV RNA及用药期间的不良反应。结果丙型肝炎肝硬化合并脾功能亢进患者采用脾切除或部分脾栓塞术治疗脾功能缓解后,给予Peg-IFNα-2a联合利巴韦林抗病毒治疗其持续病毒学应答率为64.51%。结论丙型肝炎肝硬化合并脾功能亢进的患者,在脾切除或部分脾栓塞术后给予Peg-IFNα-2a联合利巴韦林治疗有较好的SVR,延缓了丙型肝炎肝硬化的进展,减少了肝衰竭及肝癌的发生。     

Structural and biological characterization of pegylated recombinant interferon alpha-2b and its therapeutic implications

The type I interferon alpha family consists of small proteins that have clinically important anti-infective and anti-tumor activity. Interferon alpha-2b (Intron A) combination therapy with ribavirin is the current standard of care for the treatment of chronic hepatitis C virus infection. A drawback to the therapy however, is the short serum half-life and rapid clearance of the interferon alpha protein. Schering-Plough has developed a semi-synthetic form of Intron A by attaching a 12-kDa mono-methoxy polyethylene glycol to the protein (PEG Intron) which fulfills the requirements of a long-acting interferon alpha protein while providing significant clinical benefits. A detailed physicochemical and biological characterization of PEG Intron revealed its composition of pegylated positional isomers and the specific anti-viral activity associated with each of them. Though pegylation appeared to decrease the specific activity of the interferon alpha-2b protein, the potency of PEG Intron, independent of protein concentration, was comparable to the Intron A standard at both the molecular and cellular level. Importantly, PEG Intron has demonstrated an enhanced pharmacokinetic profile in both animal and human studies. Recently, PEG Intron in combination with ribavirin has been shown to be very effective in reducing hepatitis C viral load and maintaining effective sustained viral suppression in patients. Because of the improved clinical benefits, it is anticipated that the PEG Intron plus ribavirin combination therapy will become the new standard of care for the treatment of chronic hepatitis C.     

Investigational drugs for hepatitis C

Importance of the field: Hepatitis C virus (HCV) infection affects 180 million people worldwide. Standard anti-HCV therapy combines effect of pegylated IFN-alpha on immune response and antiviral activity of ribavirin. Sustained virological response rate achieved with this standard of care medication is around 50% for HCV genotype 1, the most prevalent worldwide genotype. So there is an obvious need to enhance efficacy of treatment.

Areas covered in this review: We describe novel treatment options studied within the recent few years, which are focused on inhibitors of HCV-specific enzymes such as NS3/4 protease and NS5B polymerase or influence host-virus interactions.

What the reader will gain: According to the most recent data, triple therapies consisted of pegylated interferons, ribavirin and protease inhibitors demonstrate significant improvement of treatment efficacy in comparison to current standard of care medication. Moreover, new forms of interferons and ribavirin, more effective, less toxic, and more convenient, become probably a fundamental component of anti-HCV therapy in the near future.

Take home message: In coming years, we can expect that triple therapy becomes a standard medication, and treatment without interferon and/or ribavirin becomes a new studied therapeutic scenario.     

Safety of direct-acting antivirals in the treatment of chronic hepatitis C

Introduction: Combination therapy with pegylated interferon, ribavirin and the two first-generation NS3/4A protease inhibitors (PIs), telaprevir (TVR) and boceprevir (BOC), is the new standard-of-care therapy for patients who are chronically infected with genotype 1 hepatitis C virus. These combinations significantly increase sustained virological response (SVR) rates, but they also increase the rates of adverse events (AEs). Appearance of significant AEs may necessitate dose reduction or discontinuation of treatment, and may impact on virological response.

Areas covered: In registration trials, IFN-related AEs were a dominant feature in both types of therapy. Some events were more frequent with PI-containing regimens, like anemia and dysgeusia with BOC and anemia, pruritus, rash and anorectal symptoms with TVR. This review addresses the early identification and management of AEs to improve tolerance, and to avoid reduction in SVR rates.

Expert opinion: Every patient will experience adverse effects to differing degrees; a systematic approach to their management can be very helpful. Early recognition and intervention can help clinicians ensure that patients are able to complete therapy where possible and achieve the goal of viral eradication. Treatment with the next generation of antivirals will improve safety and efficacy.     

A randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in the re-treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin

BACKGROUND: There is yet no established treatment for chronic hepatitis C patients non-responder to standard interferon and ribavirin. AIM: To evaluate efficacy and safety of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in such patients. METHODS: 161 non-responders to standard interferon and ribavirin were randomized into two groups: 81 patients (Group 1) were given weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily for 12 months, 80 patients (Group 2) received weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily and amantadine 200 mg/daily for 12 months. RESULTS: At the end of follow-up, HCV-RNA was negative in 29.6% of Group 1 and in 21.2% of Group 2 patients (P = 0.22). Patients with genotypes 1 and 4 responded better to bi-therapy (21.7%) than to triple therapy (17.3%, P = 0.5) while among patients with genotypes 2 and 3 there was a trend towards a higher sustained virological response rate when retreated with triple treatment (80% vs. 75%, P = 0.82). On multivariate analysis, genotype 1 or 4, high body mass index and >20% reduction of Peg-interferon were associated with the treatment failure. CONCLUSIONS: The addition of amantadine does not improve the overall SVR rate in non-responder patients retreated with Peg-IFN and ribavirin; however, about 30% of non-responders may achieve a sustained response, in particular patients with genotypes 2 and 3 show a high SVR (75%).     

Cost effectiveness of peginterferon alpha-2a plus ribavirin versus interferon alpha-2b plus ribavirin as initial therapy for treatment-naive chronic hepatitis C

INTRODUCTION: In adults with previously untreated chronic hepatitis C (CHC), the combination of peginterferon alpha-2a plus ribavirin produces a higher rate of sustained virological response (SVR) than interferon alpha-2b plus ribavirin, but it is still unproven whether this increase is cost effective. The objective of this study was to determine if the gain in SVR with peginterferon alpha-2a plus ribavirin is worth the incremental cost. METHODS: We constructed a Markov model of disease progression in which cohorts of patients received peginterferon alpha-2a plus ribavirin or interferon alpha-2b plus ribavirin for 48 weeks (hepatitis C virus [HCV] genotype 1 and non-1 patients with fibrosis) or 24 weeks (genotype non-1 patients without fibrosis), and were followed for their expected lifetimes. The reference patient was a 45-year-old male with CHC without cirrhosis. The SVRs with peginterferon alpha-2a plus ribavirin and interferon alpha-2b plus ribavirin used to populate the model were 46% and 36% for patients infected with HCV genotype 1 and 76% and 61% for patients infected with HCV non-1 genotypes, respectively. QOL and costs for each health state were based on literature estimates and on Italian treatment patterns. Costs were in 2002 euros and benefits were discounted at 3%. Sensitivity analyses on key clinical and economic parameters were performed. The analysis was reported from the perspective of the Italian National Health Service. RESULTS: In patients infected with HCV genotype 1, peginterferon alpha-2a plus ribavirin increased life-years (LYs) by 0.78 years and QALYs by 0.67 years, compared with interferon alpha-2b and ribavirin. The incremental cost per LY and QALY gained was euro9433 and euro10 894, respectively. In patients infected with HCV non-1 genotypes, peginterferon alpha-2a plus ribavirin increased LYs by 1.17 and QALY by 1.01 years, compared with interferon alpha-2b plus ribavirin. The incremental cost per LY and QALY gained was euro3261 and euro3766, respectively. Using genotype distribution estimates, the weighted average ICER for all genotypes was euro6811 per LY gained and euro7865 per QALY gained. CONCLUSION: Our model suggests that peginterferon alpha-2a plus ribavirin is cost effective compared with conventional interferon alpha-2b plus ribavirin for treatment of naive adults with CHC, regardless of HCV genotype, under a wide range of assumptions regarding treatment effectiveness and costs.     

Antiviral treatment of chronic hepatitis C

The therapy of the chronically hepatitis C virus infection is still a major challenge for the attending physician. Standard therapy regimen implements the combination of pegylated interferon alpha and ribavirin. Duration of therapy is individualized according to the infecting HCV genotype and on the viral response. However, only in 50-80% (dependent on the HCV genotype) treatment will be successful. The development of so called "direct-acting antivirals"(DAA) will provide new options and this was achieved by the approval of two inhibitors of the HCV protease. Boceprevir and telaprevir give hope especially for patients infected with the worse to treat HCV genotype 1. In order to reduce the risk of antiviral resistance these drugs are given in combination with pegylated interferon and ribavirin only.     

Cost-efficacy analysis of peginterferon alfa-2b plus ribavirin compared with peginterferon alfa-2a plus ribavirin for the treatment of chronic hepatitis C

OBJECTIVE: Combination therapy with pegylated interferon (Peg) and ribavirin (RBV) is the standard of care for the treatment of chronic hepatitis C virus (HCV) infection. This analysis compares the cost efficacy of treatment with pegylated interferon alfa-2b plus ribavirin (Peg-2b plus RBV) with pegylated interferon alfa-2a plus ribavirin (Peg-2a plus RBV) in hypothetical cohorts of 100 chronic HCV patients comprised 75% of genotype 1. METHODS: A decision analysis model was constructed from the viewpoint of a managed care organization to compare Peg-2b plus RBV (1.5 mcg per kilogram per week plus RBV 800 mg per day) and Peg-2a plus RBV (180 mcg per week plus RBV 1,000-1,200 mg per day) pursuant to the label dosing approved by the U.S. Food and Drug Administration. The model also included the so-called weight-based dosing regimen with Peg-2b plus RBV (1.5 mcg per kilogram per week plus RBV 10.6 mg/kg per day). Patient weight was assumed to be 80 kg. For purposes of this analysis, early virologic response (EVR), defined as viral negative or 2-log drop in viral load, was assessed at 12 weeks for only genotype 1 patients, and nonresponders were assumed to discontinue therapy. The positive predictive value (PPV) was calculated for each treatment group for genotype 1 patients, which is determined from the values for EVR and sustained viral response (SVR). Genotype 2 and genotype 3 patients were assumed to be treated for 24 weeks. Treatment duration and efficacy data were obtained from the published literature. Product pricing was based on average wholesale price, October 2004, and sensitivity analysis was performed using prices from the Federal Supply Schedule. Economic outcomes were determined from hypothetical 100-patient cohorts assumed to be comprised 75% of genotype 1 HCV. RESULTS: Taking into account both EVR and SVR, the PPV for genotype 1 patients was 0.63 and 0.57 for Peg-2b plus RBV and Peg-2a plus RBV, respectively. The proportion of treated patients achieving SVR would be nearly identical, (53.6%) and (53.8%) for Peg-2a plus RBV and Peg-2b plus flat RBV, respectively. For Peg- 2b plus weight-based RBV, the proportion of patients achieving SVR was higher (61.4%). Consequently, this leads to fewer overall treatment weeks for the Peg- 2b plus RBV cohorts. Therefore, the cost per successful treatment (defined as SVR) was 19.4% less (37,638 US dollars) for Peg-2b plus flat dosing of RBV as compared with Peg-2a plus RBV (46,717 US dollars). When Peg-2b plus RBV was dosed 1.5 mcg per kilogram per week plus RBV 10.6 mg/kg/day, then the cost per SVR was 39,045 US dollars. The cost for the 100-patient cohort was 2,024,846 US dollars for Peg-2b plus RBV, 2,397,529 US dollars for Peg-2b plus weight-based RBV, and 2,505,317 US dollars for Peg-2a plus RBV. This difference is due to a lower PPV in the Peg-2a plus RBV groups and hence more patients treated in spite of a low probability of achieving SVR. CONCLUSION: The results of this cost-efficacy analysis suggest that treating HCV genotype 1 patients with Peg-2b plus RBV may result in savings to a health care system because fewer of these patients are treated beyond 12 weeks when achieving sustained viral clearance is unlikely.     

Effectiveness of pegylated interferon/ribavirin combination in 'real world' patients with chronic hepatitis C virus infection

Background  Clinical trials have shown that the combination of pegylated interferon/ribavirin induces a sustained virological response in 54–63% of patients with chronic hepatitis C virus infection, but its effectiveness in day-to-day clinical practice is less clear.
Aim  To verify if the efficacy of pegylated interferon/ribavirin combination in 'real world' patients is comparable to that observed in trials.
Methods  The medical records of 397 consecutive naïve patients with chronic hepatitis C virus infection treated with pegylated interferon/ribavirin combination in nontertiary hospital settings were reviewed in order to assess the response to anti-viral treatment.
Results  The sustained virological response rate achieved in this population was similar to that recorded in registration trials (total population: 64%; genotype 1: 46%; genotypes 2–3: 84%). Also, the premature discontinuation rate (15%) was similar to that observed in registration trials, but there were fewer dose reductions in one or both medications (26%). We confirmed the association between adherence and sustained virological response among the patients infected with hepatitis C virus genotype 1 who were treated for ≥80% of the planned duration of treatment.
Conclusion  The effectiveness of pegylated interferon/ribavirin therapy and factors predicting an sustained virological response in everyday clinical practice mirror those reported in randomized-controlled studies.