Addition of PEG-interferon to long-term nucleos(t)ide analogue therapy enhances HBsAg decline and clearance in HBeAg-negative chronic hepatitis B : Multicentre Randomized Trial (PAS Study)
© 2024 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd..
We studied whether 48 weeks of PEG-IFN alfa-2a add-on increases HBsAg-decline and clearance in HBeAg-negative patients on long-term nucleo(s)tide analogue (NA) therapy. In this investigator-initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg-negative patients treated with NA > 12 months, with HBVDNA < 200 IU/mL, were enrolled. Patients were randomized 2:1 to 48 weeks of PEG-IFN alfa-2a add-on (180 μg per week) or continued NA-monotherapy with subsequent follow-up to Week 72. Endpoints were HBsAg decline (≥1 log10 IU/mL) and HBsAg clearance at Week 48. Of the 86 patients in the modified-intention-to-treat analysis, 58 patients received PEG-IFN add-on, and 28 continued NA monotherapy. At Week 48, 16(28%) patients achieved HBsAg decline ≥1 log10 in the add-on arm versus none on NA-monotherapy (p < .001), and HBsAg clearance was observed in 6 (10%) PEG-IFN add-on patients versus 0% NA-monotherapy (p = .01). HBVRNA was only detected in 2% after PEG-IFN treatment versus 19% in NA-monotherapy (p = .002) at Week 48. PEG-IFN add-on therapy was well tolerated in majority of patients. Low baseline HBsAg levels (<10 IU/mL) identified patients most likely to achieve HBsAg loss with PEG-IFN add-on, whereas an HBsAg level > 200 IU/mL at on-treatment Week 12 was highly predictive of non-response (NPV = 100%). Addition of PEG-IFN to long-term NA enhanced HBsAg decline and increased the chance of HBsAg clearance in HBeAg-negative patients on long-term NA. On-treatment HBsAg levels >200 IU/mL identify patients unlikely to benefit from PEG-IFN add-on and could be used as a potential stopping-rule for PEG-IFN therapy. Our findings support further exploration of immune modulation add-on to antiviral therapy, preferably using response-guided strategies, to increase functional cure rates in patients with CHB.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Journal of viral hepatitis - 31(2024), 4 vom: 08. Apr., Seite 197-207 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Farag, Mina S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 17.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/jvh.13918 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Addition of PEG-interferon to long-term nucleos(t)ide analogue therapy enhances HBsAg decline and clearance in HBeAg-negative chronic hepatitis B |b Multicentre Randomized Trial (PAS Study) |
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| 500 | |a Date Revised 17.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd. | ||
| 520 | |a We studied whether 48 weeks of PEG-IFN alfa-2a add-on increases HBsAg-decline and clearance in HBeAg-negative patients on long-term nucleo(s)tide analogue (NA) therapy. In this investigator-initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg-negative patients treated with NA > 12 months, with HBVDNA < 200 IU/mL, were enrolled. Patients were randomized 2:1 to 48 weeks of PEG-IFN alfa-2a add-on (180 μg per week) or continued NA-monotherapy with subsequent follow-up to Week 72. Endpoints were HBsAg decline (≥1 log10 IU/mL) and HBsAg clearance at Week 48. Of the 86 patients in the modified-intention-to-treat analysis, 58 patients received PEG-IFN add-on, and 28 continued NA monotherapy. At Week 48, 16(28%) patients achieved HBsAg decline ≥1 log10 in the add-on arm versus none on NA-monotherapy (p < .001), and HBsAg clearance was observed in 6 (10%) PEG-IFN add-on patients versus 0% NA-monotherapy (p = .01). HBVRNA was only detected in 2% after PEG-IFN treatment versus 19% in NA-monotherapy (p = .002) at Week 48. PEG-IFN add-on therapy was well tolerated in majority of patients. Low baseline HBsAg levels (<10 IU/mL) identified patients most likely to achieve HBsAg loss with PEG-IFN add-on, whereas an HBsAg level > 200 IU/mL at on-treatment Week 12 was highly predictive of non-response (NPV = 100%). Addition of PEG-IFN to long-term NA enhanced HBsAg decline and increased the chance of HBsAg clearance in HBeAg-negative patients on long-term NA. On-treatment HBsAg levels >200 IU/mL identify patients unlikely to benefit from PEG-IFN add-on and could be used as a potential stopping-rule for PEG-IFN therapy. Our findings support further exploration of immune modulation add-on to antiviral therapy, preferably using response-guided strategies, to increase functional cure rates in patients with CHB | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a HBVRNA | |
| 650 | 4 | |a HBsAg loss | |
| 650 | 4 | |a functional cure | |
| 650 | 4 | |a novel agents | |
| 650 | 4 | |a short-term PEG-IFN | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Hepatitis B Surface Antigens |2 NLM | |
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| 700 | 1 | |a van Campenhout, Margo J H |e verfasserin |4 aut | |
| 700 | 1 | |a Sonneveld, M J |e verfasserin |4 aut | |
| 700 | 1 | |a Fung, Scott |e verfasserin |4 aut | |
| 700 | 1 | |a van Erpecum, Karel J |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, David K |e verfasserin |4 aut | |
| 700 | 1 | |a Verhey, Elke |e verfasserin |4 aut | |
| 700 | 1 | |a de Man, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a De Knegt, Robert J |e verfasserin |4 aut | |
| 700 | 1 | |a Brouwer, Johannes T |e verfasserin |4 aut | |
| 700 | 1 | |a Baak, Hubertus C |e verfasserin |4 aut | |
| 700 | 1 | |a Feld, Jordan J |e verfasserin |4 aut | |
| 700 | 1 | |a Liem, Kin Seng |e verfasserin |4 aut | |
| 700 | 1 | |a Boonstra, André |e verfasserin |4 aut | |
| 700 | 1 | |a Hansen, Bettina E |e verfasserin |4 aut | |
| 700 | 1 | |a Janssen, Harry L A |e verfasserin |4 aut | |
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