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Journal of Viral Hepatitis, 2010, 17, 459–468 Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plusribavirin in the daily routine treatment of patients with chronichepatitis C in Germany: The PRACTICE Study T. Witthoeft,1 D. Hueppe,2 C. John,3 J. Goelz,4 R. Heyne,5 B. Moeller,5 G. Teuber,6 S.
Wollschlaeger,7 A. Baumgarten,8 K.-G. Simon,9 G. Moog,10 N. Dikopoulos11 and S. Mauss121Private Gastroenterological Practice, Stade; 2Centre of Gastroenterology, Herne; 3Centre of Gastroenterology, Berlin; 4Practice Centre Kaiserdamm, Berlin; 5Centre of Gastroenterology and Hepatology, Berlin; 6Johann Wolfgang Goethe University, Frankfurt/Mai; 7Hospital Dresden Friedrichstadt, Dresden; 8General Practice, Berlin; 9Centre of Gastroenterology, Leverkusen; 10Centre of Gastroenterology, Kassel; 11Department for Internal Medicine I, University of Ulm, Ulm; and 12Centre for HIV and Hepatogastroenterology, Dusseldorf, Germany Received October 2009; accepted for publication November 2009 SUMMARY. In randomized clinical trials, treatment with 59.9% of patients in Group A and 55.9% in Group B peginterferon plus ribavirin (RBV) results in a sustained achieved an SVR (P £ 0.051). In genotype 1-infected pa- virological response (SVR) in around half of hepatitis C virus tients matched by baseline parameters and cumulative RBV genotype 1-infected and 80% of genotype 2/3-infected dose, SVR rates were 49.6% and 43.7% for Group A and individuals. This study aimed to evaluate efficacy and tol- Group B, respectively (P £ 0.047); when matched by base- erability of peginterferon alfa-2a plus RBV compared with line parameters and RBV starting dose, SVR rates were peginterferon alfa-2b plus RBV for the treatment of chronic 49.9% and 44.6%, respectively (P = 0.068). Overall, 21.8% hepatitis C in routine clinical practice. The intent-to-treat of group A and 29.6% of group B patients discontinued cohort consisted of 3414 patients treated with either treatment (P £ 0.0001). The efficacy and tolerability of peginterferon alfa-2a plus RBV (Group A) or peginterferon peginterferon plus RBV in this large cohort of patients alfa-2b plus RBV (Group B) in 23 centres participating in the treated in routine daily practice was similar to that in large, multicentre, observational PRACTICE study. Collected randomized clinical trials. In matched pairs analyses, data included baseline characteristics, treatment regimen, more patients achieved an SVR with peginterferon alfa-2a RBV dose and outcome. Rates of early virological response, compared with peginterferon alfa-2b.
end of treatment response and SVR were 76.6%, 75.7% and52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group Keywords: chronic hepatitis, HCV, PCR, pegylated interferon, B, respectively. In patients matched by baseline parameters, ribavirin, sustained virological response, viral load.
Hepatitis C virus (HCV) infection is a major public health numbers of intravenous drug users and immigration from problem, with around 170 million individuals infected endemic areas have led to an increase in the incidence of worldwide [1]. Up to 85% of infected individuals go on to HCV infection in Europe over recent years [2,3]. Peginter- develop chronic HCV (CHC) infection, with an associated risk feron plus ribavirin (RBV) represents the gold standard of progression to cirrhosis, end-stage liver disease and treatment for CHC. The primary measure of treatment suc- hepatocellular carcinoma. Despite improvements in blood cess is sustained virological response (SVR), i.e. negative transfusion safety and healthcare conditions, the increase in HCV RNA 6 months after the cessation of therapy, which isassociated with a >99% chance of being virus-free 5 yearslater [4]. In large randomized controlled trials (RCTs), SVR Abbreviations: BMI, body mass index; CHC, chronic HCV; EOT, end was achieved by almost half of genotype 1-infected and of treatment; EVR, early virological response; HVL, high viral load; IDEAL, Individualized Dosing Efficacy vs. flat dosing to Assess around 80% of genotype 2/3-infected individuals [5–7].
optimaL pegylated interferon therapy; ITT, intent to treat; LVL, low Results from such trials form the basis of national and viral load; RBV, ribavirin; SVR, sustained virological response.
international guidelines that provide recommendations ondosing, treatment duration and patient management [8–12].
Correspondence: Priv.-Doz. Dr. Thomas Wittho¨ft, Private Gastroen- terological Practice Stade, Wallstrasse 38, 21682 Stade, Germany.
However patients included in RCTs are necessarily subject to strict inclusion and exclusion criteria that may not reflect the more complex clinical picture seen in patients in the clinical setting compared to that seen in clinical trials. We Ôreal-lifeÕ setting. In addition, the clinical trial situation pro- also aimed to assess response and tolerability in patients vides a high level of medical and support care that tends to matched in terms of baseline characteristics and RBV dose to maximize patient compliance. This, together with controlled directly compare the effects of the two peginterferons.
management of side effects and dose reductions, potentiallycontributes to improved compliance that is known to influ- ence the success of treatment [13,14]. Given these factors, itis possible that results may vary between RCT results and PRACTICE is a retrospective study of patients with CHC managed at 23 German gastroenterological centres with high Two forms of peginterferon, peginterferon alfa-2a (40KD) treatment rates (‡20 patients/year) between 2000 and 2007.
and peginterferon alfa-2b (12KD), are commercially avail- This study investigated patients from the total PRACTICE data able, which differ in terms of their pharmacokinetic, viral set who had undergone treatment with either peginterferon kinetic and tolerability profiles [15,16]. Evaluation of any alfa-2a (40KD) (PEGASYSÒ; Roche, Welwyn Garden City, UK) differences in efficacy between the two compounds is difficult plus RBV (CopegusÒ; Roche, Grenzach-Wyhlen, Germany) or because of the lack of direct comparability between clinical peginterferon alfa-2b (12KD) (PegIntronÒ; Schering-Plough, trials and issues around trial design in direct comparison Bruxelles, Belgium) plus RBV (RebetolÒ; Schering-Plough). As studies. A range of factors are known to affect response to this study was retrospective, dosing and treatment duration peginterferon plus RBV, including baseline characteristics were not controlled but reflected the clinical practice of the such as HCV genotype, viral load, age and degree of fibrosis physician and/or treatment centre at the time the patient was [17]. In addition, RBV dose has also been shown to affect treated. Patient selection for submission to the database was entirely at the clinicianÕs discretion; no restrictive parameters [6,14,18–20]. RBV dose can be a confounding factor in were set other than diagnosis of CHC. Data collection was comparative trials. In the Individualized Dosing Efficacy vs.
performed via an online e-CRF. Baseline parameters included flat dosing to Assess optimaL pegylated interferon therapy sex, age, weight/body mass index (BMI), duration of infection, (IDEAL) trial [21], for example, differences in RBV starting histology at baseline, concomitant diseases, drug abuse and dose and dose reduction regimens introduce bias that pre- concomitant medication; virological parameters included vents direct comparison between the two peginterferons.
HCV genotype, viral load, early virological response (EVR [‡2- Recommended combination treatment regimens for each log10 drop in HCV RNA and/or HCV RNA £50 IU/mL and/or peginterferon use different RBV dosing [22,23], and there- HCV RNA qualitatively undetectable at week 12]), end of fore studies that use recommended regimens cannot provide treatment response (EOT) and SVR (HCV RNA £50 IU/mL a direct, head-to-head comparison, although they do offer and/or HCV RNA undetectable after 24 weeks of follow-up).
comparisons between the specific combination regimens. Toovercome the bias introduced by RBV dosing regimen, a recent Italian study gave all patients treated with eitherpeginterferon the same RBV dose based on body weight, with The statistical analysis was descriptive to reflect the clinical RBV dose reduction being managed identically in both routine as intended by the clinicians. Summary statistics groups of patients [24]. However, if the two peginterferons (mean, median, standard deviation, 25th percentile, 75th are to be directly compared, baseline and treatment-related percentile, minimum, maximum, number of values) or fre- factors must be taken into account [25].
quencies and proportions were assessed for all collected The Pegylated Interferons and RBV: Analysis of CHC parameters. A matched pairs population was created to Treatment In Centres of Excellence (PRACTICE) study is a control the variability of baseline characteristics that influ- German nationwide retrospective, observational study anal- ence response. A second matched pairs population was ysing the response to hepatitis C treatment in routine clinical created to control for baseline characteristics and RBV dose.
practice. PRACTICE includes patients treated between 2000 Analyses were calculated with SPSS for Windows Release and 2007 in 23 gastroenterological centres with excellent 12.0.2 (Chicago, IL, USA), Testimate Version 6.4.27 treatment expertise (at least 20 CHC patients treated per year).
(Institute for Data Analysis and Study Planning, Gauting/ This retrospective study provides an important source of Munich, Germany) and Matched Version 1.1 (Institute for information regarding a cross section of HCV patients treated Medical Statistics and Documentation, Erlangen, Germany).
under real-life conditions. Such patients are likely to beexposed to factors that may potentially influence outcome which are not experienced by patients participating in highlycontrolled clinical trials. Using data from the PRACTICE Patients were matched in pairs, one from each treatment cohort, we aimed to evaluate the efficacy and tolerability of group: Group A included those patients treated with peginterferon alfa-2a plus RBV and peginterferon alfa-2b peginterferon alfa-2a and Group B those treated with plus RBV for the treatment of CHC patients in a Ôreal-worldÕ Peginterferon plus RBV in routine practice 56 patients subsequently diagnosed with acute hepatitis C To account for variations in response to peginterferon that and not chronic hepatitis C were excluded from the analysis.
may result from baseline characteristics, patients were The intent-to-treat population therefore consisted of 3414 matched according to the following criteria: age difference patients: 1755 in Group A and 1659 in Group B. Patients £3 years; HCV genotype (based on predominant infecting were then assigned to matched pairs based on the criteria genotype); category of viral load (low viral load or high viral given earlier. Those patients who could not be allocated to a load; cut-off: £400.000 IU/mL); BMI (difference £2 kg/m2); pair were excluded from the analysis. The resulting Matched Pairs I dataset consisted of 2378 patients (1189 from Group RBV-combination therapy, peginterferon-RBV-combination A and 1189 from Group B); of these 1672 (836 from each Group) were included in the Matched Pairs II analysis.
treatment); presence of drug substitution treatment and Groups A and B were well matched in terms baseline and demographic data (Table 1) and in terms of concomitantmedication (Table 2). The majority of patients were treatment naive [89.0%, intent to treat (ITT)]; 5.8% had relapsed, 4.9% To account for the effects of variations as a result of RBV were nonresponders and 0.3% had been both relapsers and dose, a further analysis was performed. In addition to the nonresponders (‡2 previous treatments). The most common criteria of Matched Pairs I, patients were matched according known sources of HCV infection were intravenous drug use (35.7%, ITT analysis) and transfusion (18.0%, ITT analysis).
>100%), where 100% dose was based on that given by the The source of infection was unknown in 33.0% of the patients.
specific RBV prescribing recommendation [22,23].
The mean duration of therapy is shown in Table 3. The percentage of patients who received £80% cumulative doseof peginterferon and of RBV (based recommended dosing B = 1686) included in the PRACTICE cohort who had Virological responses to treatment in the various groups are undergone treatment with peginterferon plus RBV were shown in Table 5. In the ITT analysis, the rate of EVR, EOT identified. Patient disposition is shown in Fig. 1. Among all, response and SVR was higher in patients in Group A com-pared with group B, although this did not reach statisticalsignificance for any measure. In the Matched Pairs I anal-ysis, the overall SVR was lower in Group B patients (55.9%)than in Group A patients (59.9%), and this differenceshowed (P = 0.051; Fig. 2). There was no significant difference inSVR between Group A and Group B when analysed bygenotype (Table 5; Fig. 1). In the Matched Pairs II analysis,the overall SVR was again higher in Group A patientscompared with Group B patients (59.1% vs 54.4%, respec-tively; P = 0.054). For genotype 1-infected patients, thepercentage of patients with an SVR in Group A was signifi-cantly higher than for Group B (49.6% vs 43.7%, respec-tively; P = 0.047) (Fig. 3). There was no significantdifference for genotype 2/3-infected patients.
Rates of EVR, EOT and SVR response were lower in patients co-infected with HIV (n = 148) compared withthose with HCV infection only. In the ITT population,29.4%, 47.4% and 34.7% of genotype 1 co-infected patientswith HIV achieved EVR, EOT response and SVR, respectively.
For genotype 2/3 co-infected patients, EVR, EOT responseand SVR rates were 85.7%, 79.2% and 58.5%, respectively.
SVR rates were higher in patients in Group A compared withGroup B (36.7% vs 31.6%, respectively, for genotype-1co-infected patients, and 63.0% vs 53.9%, respectively, for ITT, intent to treat; MP, matched pairs; BMI, body mass index; HVL, high viral load (>400 000 IU/mL); LVL, low viral load(£400 000 IU/mL). *Present in >5% of overall population.
prescribing information, significantly more genotype 1-in- Treatment discontinuations (ITT analysis) fected patients in Group A achieved an SVR compared with Overall, significantly fewer patients discontinued therapy Group B. However, as the prescribed RBV starting dose and before the EOT in Group A compared with Group B (21.8% dose reduction regimens are different for the two different RBV vs 29.6%; P £ 0.0001). The main reasons for withdrawal preparations [22,23], this method may not have resulted in were (multiple reasons were possible for each patient) viro- matching in terms of absolute RBV dose. We therefore per- logical nonresponse (Group A 12.7%; Group B 19.3%); poor formed an additional analysis of genotype 1-infected patients tolerability (Group A 4.0%; Group B 4.3%); patient request matched by the criteria of Matched Pairs I plus initial RBV (Group A 2.2%; Group B 3.1%) and noncompliance (Group dose, which included the evaluation of any dose reductions and dose reduction strategy (i.e. amount of reduction). Thepotential effect of body weight on RBV starting dose wascontrolled as patients were matched for BMI deviation Ribavirin dose and dose adjustment – Matched Pairs III <2 kg/m2 as per Matched Pair I criteria. In all, 579 matched In the Matched Pair II analysis, where patients were pairs were included in this analysis (Matched Pairs III).
matched according to cumulative RBV dose as defined by Starting dose of RBV was 600 mg in 0.2%, 800 mg in Peginterferon plus RBV in routine practice ITT, intent to treat; MP, matched pairs. *In >1% of cohort.
26.4%, 1000 mg in 54.7% and 1200 mg in 18.6% of resulted in a cure (SVR) in over half of all patients, a figure patients in each Group. The majority of patients (90.2% in similar to that reported in pivotal clinical trials [5–7]. Good Group A and 87.2% in Group B) did not require RBV dose SVR rates were achieved despite the fact the study included reduction; 20 (3.5%) and 19 (3.3%) patients in Group A and patients such as HIV infected patients and intravenous drug Group B, respectively, received RBV dose reductions of abusers who are generally considered to be less easy to treat ‡400 mg, and 31 (5.4%) and 52 (9.0%), respectively, and would have been excluded from clinical trials. The received RBV dose reductions of 200 mg (P = 0.1148 for overall rates of EVR, EOT and SVR were higher in those difference in dose reduction between groups). Average time patients treated with peginterferon alfa-2a plus RBV com- to first dose reduction was similar between both groups pared with peginterferon alfa-2b plus RBV. In patients (92.1 days in Group A and 94.5 days in Group B). In the matched by baseline characteristics, treatment with peg- Matched Pairs III analysis, a higher proportion of genotype interferon alfa-2a plus RBV was associated with a higher 1-infected patients achieved SVR in Group A compared with rate of SVR than peginterferon alfa-2b plus RBV. In addition, Group B when matched by RBV starting dose, although this when patients were matched in terms of RBV dose, both did not reach statistical significance (49.9% vs 44.6%, by starting dose and as a proportion of cumulative dose based on prescribing information, more genotype 1-infectedpatients achieved SVR with peginterferon alfa-2a plus RBVcompared with peginterferon alfa-2b plus RBV.
Data from randomized clinical trials form the basis of In this large open-label cohort study of patients with chronic treatment guidelines and inform clinicians and healthcare hepatitis C treated in clinical community settings over a workers on individual patient management. However, clini- period of 7 years, treatment with peginterferon plus RBV cal trial populations by necessity are defined and restricted,and the trial process itself involves the use of clear protocols,for example, concerning dose reductions or treatment. The support and monitoring a patient receives during a clinicaltrial is also more likely to improve compliance with treat- ment, which is an important contributor to a successful outcome. As such, the clinical trial situation may not fully reflect real-life clinical practice with its more diverse, complex patient population, variability in access and support mech- anisms, and possibly less well-defined protocols in routine practice. Cohort studies such as the current study aretherefore important to assess how well clinical trial data transfer to routine practice. In the current study, 57.9% Table 4 Patients (%) who received £80% cumulative dose of peginterferon or ribavirin (RBV) dose of patients overall achieved an SVR: 46.5% of genotype The current study also suggests that treatment with 1-infected patients and 77.3% of genotype 2/3-infected. This peginterferon alfa-2a may result in a higher rate of SVR in compares favourably with pivotal clinical trials that reported patients treated under routine clinical conditions. For a valid rates of 42–46% in genotype 1-infected patients and 76–82% comparison of peginterferon regimes to be made, it is in genotype 2/3-infected patients [5–7,26,27]. The findings important to match patient groups not only according to of this study are also in line with those from other retro- baseline factors but also according to RBV dose. Genotype spective analyses of HCV-infected patients treated in routine and viral load are the most significant factors associated with clinical practice where overall SVR rates of 49–66% have SVR, but other baseline factors such as CHC treatment been reported, with rates of 37–61% in genotype 1-infected history, co-infection with HIV, BMI and age have also been and around 70% of genotype 2-infected patients [28–32].
shown to influence response [17,31,35,36]. RBV dose is also The SVR rates achieved by HIV/HCV co-infected patients in important both to early viral decline and EVR, and to the the current study not only were lower than those in HCV prevention of relapse and so SVR [35]. There is evidence that monoinfected patients as would be expected, but also RBV dose at the start of and early in the course of treatment compared favourably to those achieved in clinical trials is predictive of SVR [19,20] and that maintenance of RBV dose during therapy is also an important factor in attaining Treatment with peginterferon plus RBV was well tolerated SVR, particularly in genotype 1-infected patients [14,37].
in the current study. Rates of discontinuation of therapy Interestingly, RBV has also been shown to be important to were similar to that reported in pivotal clinical trials SVR in recent studies of triple antiviral regimens [38] – the (14–21%) [5–7] and were within the range reported by so-called specifically targeted antiviral therapy for hepatitis C other cohort studies of peginterferon plus RBV in clinical or STAT-C – further underlining its importance in inter- practice (11–33%) [28,31,32]. This current study therefore feron-based treatment regimens. We found that EVR, EOT adds to the growing volume of data demonstrating that the and SVR rates were all higher for peginterferon alfa-2a efficacy and tolerability of peginterferon plus RBV can be compared with peginterferon alfa-2b, although this did not similar in everyday clinical practice as that reported in reach significance in the ITT analysis. Where patients were matched by potentially confounding baseline characteristics, EVR, early virological response; EOT, end of treatment; SVR, sustained virologicalresponse; ITT, Intent to treat; MP, Matched pairs; P values for A vs. B.
Underlined P values reflect 5% level of significance: *P = 0.051;  P = 0.054;àP = 0.047.
Peginterferon plus RBV in routine practice side-effect profiles may affect adherence and so SVR. Therewas a significantly higher discontinuation rate with pegin-terferon alfa-2b compared with peginterferon alfa-2a in thecurrent study, predominantly as a result of higher virologicalnonresponse, although the rate of Ôpoor tolerabilityÕ wassimilar between groups. Consensus Guidelines for the treat-ment of CHC with peginterferon plus RBV have been avail-able since 2002 [8,9,11,12], with German guidelines beingpublished in 2004 [10]. The findings from this study suggestthat, overall, clinicians who took part in PRACTICE werelargely following guidelines in terms of treatment duration,with a mean duration of therapy of around 24 weeks for Fig. 2 Sustained virological response in Matched Pair Ianalysis (matched by baseline factors).
genotype 2/3 patients and 40 weeks for genotype 1 patients,although the mean duration of therapy in genotype 1patients was shorter in the peginterferon alfa-2b group. Inaddition, the number of genotype 1 patients who received£80% cumulative interferon dose was higher at over 50% inthe peginterferon alfa-2b group, which may also havecontributed to poorer outcome.
Several recent trials have also reported higher SVR rates with peginterferon alfa-2a plus RBV compared with pegin-terferon alfa-2b plus RBV. A prospective, randomized,independent Italian study, in which a standard initial doseof RBV and consistent strategies for dose reduction wereused for both peginterferons, found that more patientstreated with peginterferon alfa-2a plus RBV significantlyachieved SVR compared with those treated with peginter- Fig. 3 Sustained virological response in Matched Pair II feron alfa-2b plus RBV (68.7% vs 54.4%, respectively; analysis (matched by baseline factors and cumulative P = 0.008) [24]. The randomized open-label Milan Safety Tolerability study also reported significantly higher SVRrates with peginterferon alfa-2a plus RBV compared with more patients achieved an SVR with peginterferon alfa-2a peginterferon alfa-2b plus RBV (66% vs 54%, respectively; plus RBV compared to peginterferon alfa-2b plus RBV in a P = 0.02) [39]. However, in the IDEAL study, SVR rates in real-life setting, and this difference approached significance.
genotype 1-infected patients were reported to be similar When matched by cumulative RBV dose, significantly more between the two different peginterferons plus RBV [40]. The genotype 1-infected patients treated with peginterferon alfa- study reported higher EOT response with peginterferon alfa- 2a achieved an SVR. Similar results were also seen when 2a plus RBV, as was also seen in the current study, but this patients were matched in terms of baseline characteristics was offset by a greater relapse rate in IDEAL that resulted in and RBV starting dose, although this did not reach signifi- the similar rate of SVR. In a subanalysis of African Ameri- cance, possibly as a result of the lower patient numbers in can patients, a particularly difficult to treat population, the Matched Pairs III analysis. As the majority of patients did included in the IDEAL trial, although SVR rates were simi- not require on-treatment dose reductions, and as reduction lar, treatment with peginterferon alfa-2a plus RBV resulted strategies appeared to be similar in those that did, it is in higher rates of rapid virological response, EVR and EOT unlikely that differences in RBV dose affected our findings.
response [41]. Given the importance of RBV to both early Interestingly, in line with results from the APRICOT and and SVR, particularly in genotype 1 patients, this effect may RIBAVIC studies [33,34], we found a higher rate of response be explained by the different RBV dosing and side-effect rate in HCV/HIV co-infected patients treated with peginter- management strategies that were used in the different feron alfa-2a compared with those treated with peginterfer- treatment arms of IDEAL, where RBV dose reductions of on alfa-2b in the ITT population of this Ôreal-lifeÕ study.
200–400 mg/day were used for those patients treated with Unfortunately, because of the small number of patients in peginterferon alfa-2b, whereas those patients treated with the Matched Pairs groups, it is not possible to interpret this peginterferon alfa-2a received an RBV dose reduction of finding further. The reasons behind the different responses 600 mg/day (as recommended in the prescribing guide- obtained using the different peginterferons is unclear. Dif- lines). Such differences make direct comparisons between ferences in pharmacokinetics and viral kinetics may impact the individual peginterferons alone impossible to make with on virological response [15,16], while differences in confidence from this study. In our study, initial RBV dose and dose reduction management were at the discretion of regimens used in daily practice in patients matched for the treating clinician and presumably reflected current possibly confounding baseline parameters.
treatment guidelines. However, it is interesting to note that, In this large, multicentre study of patients treated with in genotype 1-infected patients matched for initial RBV dose peginterferon plus RBV over 7 years in Ôreal-worldÕ clinical and for BMI, RBV dose reductions on-treatment were very conditions, efficacy and tolerability were similar to that similar between patient groups treated with peginterferon described in industry-sponsored registration trials, despite alfa-2a or peginterferon alfa-2b. The majority of patients the high selection and support provided to patients enrolled received dose reductions of 200 mg, independent of the in such trials. When patients in this study were matched in prescribing information that recommends reduction of terms of baseline characteristics and according to RBV dose, 600 mg. These findings therefore suggest that differences in both of which are known to affect the outcome of pegin- RBV dose reduction did not contribute to the differences terferon therapy, data suggest that more patients treated seen in SVR and also that a more conservative RBV dose with peginterferon alfa-2a in routine daily practice achieve reduction strategy is employed in routine practice than is SVR compared with peginterferon alfa-2b.
recommended in prescribing recommendations. Overall,therefore, data from our study support those of studies which suggest that patients treated with peginterferon alfa-2a may be more likely to achieve an SVR compared with We express our gratitude to all investigators who partici- those who receive peginterferon alfa-2b. Further evaluation is required to investigate possible reasons for the apparentdifferences in treatment success in the current study.
Although retrospective studies are subject to a range of limitations compared with prospective studies, they do Dietrich Hueppe has served as a speaker, a consultant and provide an important source of descriptive information an advisory board member for Roche, Essex, Gilead, Bristol- pertaining to treatment under Ôreal-lifeÕ conditions and over Myers Squibb and Novartis. Christine John has received an longer time periods. In particular, they provide the oppor- honorarium and expenses from Roche for the current study tunity to assess whether success rates (in this case SVR) and has received travel grants from Roche, Gilead and obtained in clinical trials can also be obtained under real-life Bristol-Myers Squibb. Joerg Goelz has served as a speaker for conditions where patients are exposed to factors not Essex, Roche, Tibotec, Gilead, Bristol-Myers Squibb, GSK, encountered in clinical trials. The major strengths of this Pfizer and Boehringer Ingelheim and has participated in study include its large size and the long time period over advisory boards for Gilead, BMS and Pfizer. Gerlinde Teuber which data had been collected. Unlike the controlled clinical has received speakerÕs fees from Bristol-Myers Squibb, Gilead trial population, this study examined an unselected cross and Essex. Sven Wollschlaeger has received speakerÕs fees section of CHC patients treated under routine Ôreal-lifeÕ from Roche, MSD, Schering-Plough, Bristol-Myers Squibb conditions and therefore is more reflective of clinical prac- and Novartis. Axel Baumgarten has served as a speaker, a tice. The use of matched pairs of patients allows for more consultant and an advisory board member for Roche, Tibo- comparability between treatment groups by accounting for tec, Bristol-Myers Squibb, GSK, Pfizer, Essex, Gilead and MSD variation in baseline factors and RBV dose that may impact and has research funding from Roche, Tibotec, GSK, Pfizer, on outcome. Limitations of the study include the fact that is Essex and Abbott for clinical study projects. Karl-Georg not possible to completely rule out potential selection bias in Simon has received speakerÕs fees from Roche, Astra, Essex, different centres when assessing suitability for treatment and Ferring and Bristol-Myers Squibb. Nektarios Dikopoulos has in selecting treatment regimens, although the use of mat- served as a speaker for Roche AG and has received speakerÕs ched pairs of patients should help overcome the latter.
fees from Roche AG. Stefan Mauss has served as a speaker Clinicians were free to decide which patients they selected for and an advisory board member for Roche, Schering-Plough, inclusion in the study, and data regarding any patients not Gilead, Bristol-Myers Squibb, Novartis, GSK and Tibotec selected for inclusion and the reasons for any such nonin- and has received grants from Roche and Abbott. All other clusion are not available. As with all retrospective studies, authors have no conflicts of interest to declare.
another potential bias may be caused by missing data, as This study was funded by Roche AG. The authors had only data that were documented by the clinicians in the complete access to the data that support this article. Funding patient records were available for inclusion in the study.
for editorial support was also provided by Roche AG.
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