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Large International, Observational Study of Patients with Chronic Hepatitis B Infection Treated with Peginterferon Alfa-2a [40KD] (PEGASYS): the S-Collate Cohort
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Reported by Jules Levin
Presented at the 20th Conference of the Asian Pacific Association for the Study of the Liver (APASL), 25-28 March 2010, Beijing, China
Marcellin P,1 Xie Y,2 Chen XP,3 Lou GQ,4 Chen YP,5 Rothe V,6 Martins EB,7 Jia J,8 Wei L9
1Service d'Hepatologie and Centre de Recherches Biologiques Beaujon (Inserm CRB3), University of Paris, Clichy, France;
2Beijing DiTan Hospital, Beijing, China; 3Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, China;
4The Sixth People's Hospital of Hangzhou, Hangzhou, China; 5The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China;
6IST GmbH, Mannheim, Germany; 7Genentech, A Member of the Roche Group, San Francisco, California, USA;
8Beijing Friendship Hospital, Capital Medical University, Beijing, China; 9Peking University People's Hospital, Department of Hepatology, Beijing, China
CONCLUSIONS
It is anticipated that the valuable data on predictors of response that will be generated from this large, multinational, non-interventional cohort study may help identify CHB patients most likely to respond to peginterferon alfa-2a and
thereby help to develop a personalized approach to therapy. The observation that HBsAg quantification is being carried out in a high proportion of samples reflects the recognition of the dual mode of action of peginterferon alfa-2a
and acknowledgment of the potential value of HBsAg level to monitor response to therapy
Summary
This international, non-interventional, observational cohort will provide 'real-life' data about the efficacy of peginterferon alfa-2a
Analysis of the database may help validate and improve predictors of sustained response in a real-life setting
Recruitment is progressing well with over 24% of the anticipated total number of patients already enrolled by the beginning of 2010
The preliminary data shown here demonstrate the variety of baseline characteristics exhibited by patients being treated with peginterferon alfa-2a and highlight the complexity of CHB. Clinical study data are beginning to show the need to provide individualized therapy for patients with CHB and it is anticipated that future results from S-Collate may provide valuable information on how this can be achieved
The data collected so far confirm that genotyping is not routinely performed in clinical practice. Encouragingly, a large proportion of patients have had serologic markers of infection quantified at baseline. The focus of many recent clinical
studies has been how to use these markers to identify the patients most likely to respond to peginterferon alfa-2a therapy.
It is envisaged that regular monitoring of these parameters during this cohort study will provide further information about the relevance of these markers in predicting post-treatment response
Background
Two large-scale international phase 3 studies demonstrated that peginterferon alfa-2a [40KD] (PEGASYS) ± lamivudine for 48 weeks results in a sustained post-treatment response in patients with chronic hepatitis B (CHB)1,2
Follow-up studies have demonstrated the durability of sustained immune control (hepatitis B e antigen [HBeAg] seroconversion in HBeAg-positive patients or hepatitis B virus [HBV] DNA ≤10,000 copies/mL in HBeAg-negative patients) achieved with pegylated interferon up to 5 years post-treatment3-5
Furthermore, sustained immune control is associated with increasing rates of hepatitis B surface antigen (HBsAg) clearance, considered to be the ultimate goal of therapy in CHB6
The ability to predict those patients most likely to respond to therapy would be of considerable benefit to treating clinicians and their patients
Recent analyses of large-scale clinical trials have shown that patients with HBeAg-positive or HBeAg-negative CHB who achieve sustained immune control following a finite course of peginterferon alfa-2a have significantly greater decreases in HBsAg during treatment compared with patients who do not, suggesting that on-treatment HBsAg quantification may be important for monitoring post-treatment response4,7,8
Given the highly controlled nature of clinical trials, it is important that such data are confirmed and reinforced in the more complex and varied setting of routine clinical practice
Objective
The international, non-interventional, S-Collate cohort study aims to assess predictors of response in patients with HBeAg-positive or HBeAg-negative CHB treated in routine clinical practice with peginterferon alfa-2a [40KD] (PEGASYS)
according to local prescribing information
Methods
This is a non-interventional/observational cohort study of patients with CHB
The S-Collate cohort will be recruited from 28 countries (Austria, Bahrain, Bangladesh, Bosnia and Herzegovina, Brazil, Bulgaria, China, Egypt, France, Germany, Hong Kong, India, Indonesia, Ireland, Jordan, Korea, Lebanon, Macedonia, Morocco, New Zealand, Pakistan, Poland, Portugal, Romania, Saudi Arabia, Thailand, United Arab Emirates, United Kingdom)
The study aims to collect data from approximately 2000 patients. It started in April 2009 and is expected to be completed in 2014
Patients treated with peginterferon alfa-2a according to local label recommendations are eligible for data collection and will be followed for up to 3 years post-treatment to assess parameters of response (Figure 1)
Figure 1. Study design
In the 24 weeks before initiation of therapy, available data will be collected for all patients for the following parameters:
· HBV DNA (quantitative)
· serum alanine aminotransferase (ALT)
· HBsAg (quantitative or qualitative)
· anti-HBs
In addition, data will be collected for HBeAg-positive patients on:
· HBeAg (quantitative and qualitative)
· anti-HBe
The same parameters are observed during the treatment and follow-up periods
Results
As of the 1st January 2010, 675 eligible patients provided informed consent and had baseline demographics recorded for at least one of the following categories: gender, ethnicity, date of birth, height or weight
The data reported here are preliminary
Of the patients included so far, 65% were from the Asia-Pacific region, 32% were from Europe and 3% were from Africa
Disease characteristics
The characteristics of CHB in patients included in the S-Collate cohort were varied (Table 2)
· The majority of patients (59.7%) were HBeAg-positive
· Only 24.4% of patients included had HBV genotype data available at baseline
· 97.3% of patients had not been vaccinated against hepatitis B
· The mode of infection was unknown in the majority of patients (61.9%).
Perinatal infection was the most frequent known route of infection
9.3% of patients had received previous treatment for CHB
Data on liver disease was available from half of the patients (309/617; 50.1%)
· Liver fibrosis was assessed either by biopsy (213/617; 34.5%) or using non-invasive techniques (96/617; 15.6%).
Non-invasive techniques specified included liver elastography or calculation of indices from blood tests
· In those with analyzed liver fibrosis assessments (N=300), 253 (84.3%) did not have cirrhosis, 34 (11.3%) had transition to cirrhosis and 13 (4.3%) had cirrhosis
Virologic assessments
Various assays were used to quantify laboratory parameters
· HBV DNA was measured mainly using the COBAS TaqMan assay (24%), COBAS AmpliPrep assay (9.7%) or other unspecified assays (65%)
· HBsAg was measured mainly using the Abbott Architect assay (56%), Roche MODULAR assay (19%), Roche Elecsys HBsAg II assay (8%) or other unspecified assays (12%)
· HBeAg was measured mainly using the Abbott Architect assay (51%), Roche MODULAR assay (20%) or other unspecified assays (12%).
Baseline levels of HBV DNA, HBsAg, HBeAg and ALT are shown in Table 3
Table 3. Baseline laboratory data for patients included in the S-Collate study by 1st January 2010
*Only data from analyses that could be converted into standard units are included
Figure 2. Baseline HBsAg levels have been quantified at baseline in the majority of patients
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