Real-life experience with first generation HCV protease inhibitor therapy in Germany: The prospective, non-interventional PAN cohort

Abstract

Background and Aims: The efficacy and safety of peginterferon alfa-2a (PEG-IFN) plus ribavirin (RBV) and either boceprevir (BOC) or telaprevir (TVR), and physician adherence to treatment algorithms were evaluated in patients included in an ongoing non-interventional study (PAN) enrolling adults with chronic hepatitis C virus (HCV) infection managed in German office-based practices.

Methods: The analysis included HCV genotype 1-infected, treatment-naïve and treatment-experienced patients treated with BOC or TVR. Demographic, treatment history, virological response, safety, and patient management data were collected.

Results: Of a total 1087 patients, 58.1 % achieved sustained virological responses (SVR). Response rates were higher in treatment-naïve (BOC 55 %; TVR 63.4 %) and prior relapse patients (BOC 63.2 %; TVR 74.5 %) versus previous null-responders (BOC 14.3 %; TVR 25 %). The most commonly reported adverse event overall was fatigue (60.6 %); 45.8 % patients experienced hemoglobin < 10 g/dL. Patients with cirrhosis had lower rates of SVR versus those without (42.9 % vs. 60.7 %, respectively), and had a higher incidence of serious adverse events (SAEs) (16.7 % vs. 8.6 %, respectively) and treatment discontinuation (44.6 % vs. 25.2 %, respectively). According to recommended response-guided treatment algorithms, about 70 % of patients were managed appropriately, 11/10 % (BOC/TVR) received unnecessarily extended therapy, and 19/7 % (BOC/TVR) received inappropriately shortened therapy.

Conclusions: The efficacy and safety of BOC- and TVR-based triple therapy in this large, “real-world” cohort were largely comparable to that reported in pivotal clinical trials, although SVR rates were lower overall. Recommended futility or treatment extension rules were violated in a substantial proportion of patients with potential implications for response, adverse events and costs.

Zusammenfassung

Hintergrund und Zielsetzungen: In der nicht-interventionellen Studie PAN, an der Patienten mit chronischer Hepatitis-C-Virus (HCV)-Infektion teilnahmen, wurde die Wirksamkeit und Sicherheit von Peginterferon alfa-2a (PEG-IFN) in Kombination mit Ribavirin (RBV) und den Proteasehemmern Boceprevir (BOC) oder Telaprevir (TVR) sowie die Einhaltung von Therapiealgorithmen durch niedergelassene Ärzte in Deutschland untersucht.

Methoden: Die Analyse schloss Patienten mit HCV-Genotyp 1-Infektion ein, die therapienaiv oder vorbehandelt (BOC oder TVR) waren. Erhoben wurden Daten zur Demografie, Vorbehandlung, virologischem Ansprechen, Sicherheit und Management der Patienten.

Ergebnisse: Insgesamt erreichten 58,1 % der 1087 Patienten ein dauerhaftes virologisches Ansprechen (SVR). Die Ansprechraten waren bei therapienaiven Patienten (BOC 55 %; TVR 63,4 %) und Relapsern (BOC 63,2 %; TVR 74,5 %) höher als bei Patienten mit Null-Response auf eine vorangegangene Therapie (BOC 14,3 %; TVR 25 %). Das unerwünschte Ereignis, über das am häufigsten berichtet wurde, war Erschöpfung (60,6 %); 45,8 % der Patienten hatten Hämoglobinwerte < 10 g/dL. Die SVR-Raten waren bei Patienten mit Zirrhose niedriger als bei Patienten ohne Zirrhose (42,9 % vs. 60,7 %), die Raten schwerer unerwünschter Ereignisse (SUE) (16,7 % vs. 8,6 %) und Therapieabbruchraten höher (44,6 % vs. 25,2 %). Ungefähr 70 % der Patienten wurden gemäß den response-gesteuerten Therapiealgorithmen behandelt, bei 11 % bzw. 10 % der Patienten (BOC/TVR) wurde die Behandlung unnötig verlängert, bei 19 % bzw. 7 % (BOC/TVR) unangemessen verkürzt.

Schlussfolgerungen: Die Wirksamkeit und Sicherheit der BOC- und TVR-haltigen Triple-Therapie in dieser großen „Real-World“-Kohorte war weitgehend vergleichbar mit den Ergebnissen der Zulassungsstudien, obwohl die SVR-Raten insgesamt niedriger waren. Bei einem beträchtlichen Teil der Patienten wurden die empfohlenen Stoppregeln oder Kriterien für eine Therapieverlängerung nicht beachtet, was potenzielle Auswirkungen auf Therapieansprechen, unerwünschte Ereignisse und Behandlungskosten hat.

Schlüsselwörter

Virushepatitis - Hepatitis C - Leber - Telaprevir - Boceprevir - Peginterferon - Kohorte

Key words

viral hepatitis - hepatitis C - liver - telaprevir - boceprevir - peginterferon - cohort study

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