Bocepreviralapú hármas kezelés hatékonyságának és biztonságosságának retrospektív elemzése előrehaladott fibrosisstádiumú, hepatitis C-vírus 1-es genotípussal fertőzött, korábban sikertelenül kezelt magyar betegeknél | Efficacy and safety of boceprevir based triple therapy in Hungarian patients with hepatitis C genotype 1 infection, advanced stage fibrosis and prior treatment failure

Absztrakt Bevezetes: Magyarorszagon 2011 es 2013 kozott korai hozzaferesi program kereteben a forgalmazo jovoltabol 155, dontően előrehaladott fibrosis stadiumu, hepatitis C-virus 1-es genotipussal fertőzott beteg kezdhetett el az akkor szamara egyeduli gyogyulasi eselyt jelentő boceprevir + pegilalt interferon + ribavirin harmas kezelest. Celkitűzes es modszer: A szerzők a terapia eredmenyessegenek es biztonsagossaganak retrospektiv ertekeleset vegeztek el egyreszt a kezeles alatti es utani virologiai valasz, masreszt a sulyos nemkivanatos, illetve terapialeallitast eredmenyező mellekhatasok alapjan. Eredmenyek: Intent-to-treat analizis szerint a 155 betegből 61 beteg valt tartosan virusmentesse (39,4%). A korabbi kettős kezelesre relabalo, parcialisan reagalo, illetve nullreagalo betegek eseteben sorrendben 59,5%, 41,4%, illetve 22,9% (p<0,05 a masik ket kategoriahoz kepest), mig cirrhosis nelkul 52,5%, cirrhosis eseten 31,3% (p<0,05 a nem cirrhosisosokhoz kepest) volt a tartos virologiai valasz. A legnehezebben kezelhető cirrhosisos es korabban nullreagalo 33 betegből 6 valt tartosan virusmentesse (18,2%). A kezeles idő előtti leallitasara elegtelen virologiai valasz miatt a betegek 31,1%-anal, mellekhatas miatt 10,3%-anal kerult sor. A sulyos nemkivanatos esemenyek gyakorisaga 9,8% volt. Ezek okai: anaemia, hasmenes, depresszio, agranulocytosis, jelentős aminotranszferaz-emelkedes, generalizalt dermatitis es sulyos gingivitis fogvesztessel, QT-szakasz-megnyulas az EKG-n, generalizalt oedemak es fulladas, uroinfekcio, Crohn-betegseg fellangolasa, Campylobacter pylori-fertőzes es a beteg altal nem toleralhato gyengeseg/faradekonysag. Nyolc betegnel volt szukseges transzfuzio, 4 beteg eritropoetin-, 1 pedig granulocytakolonia-stimulalo faktor kezelesben reszesult. A programban halalesetet nem jelentettek. Kovetkeztetesek: A 2011–2013-ban hazankban elerhető, legkorszerűbbek koze tartozo bocepreviralapu harmas kezelessel a betegek jelentős resze ert el veglegesnek tekinthető virusmentesseget. A kezelesek a torzskonyvezesi vizsgalatokbol megismert eredmenyesseggel es – esetenkent sulyos – mellekhatasokkal jartak, amely utobbiak jelentősen korlatoztak a terapia sikeresseget. Orv. Hetil., 2016, 157(34), 1366–1374. | Abstract Introduction: During 2011 and 2013, 155 Hungarian hepatitis C genotype 1 infected patients, mostly with advanced liver fibrosis, who did not respond to prior peginterferon + ribavirin dual therapy, started boceprevir based triple therapy in an early access program. Aim and method: Efficacy and safety of the therapy was retrospectively assessed based on sustained virologic responses, as well as on frequency and type of serious adverse events and of those leading to therapy discontinuation. Results: In an intent-to-treat analysis 39.4% patients (61/155) reached sustained virologic response. Amongst pervious relapsers, partial responders and null-responders 59.5%, 41.4 % and 22.9% (p<0.05 compared to the other two categories) reached sustained virologic response, respectively, while amongst non-cirrhotics and cirrhotics 52.5% and 31.3% (p<0.05 compared to the non-cirrhotics) achieved sutained virologic response, respectively. Six out of the 33 most difficult to cure patients (previous null responder and cirrhotic) have reached sustained virologic response (18.2%). Frequency of early discontinuations due to insufficient virologic response was 31.1%, while due to adverse event 10.3%. Reported frequency of serious adverse event was 9.8%. These events represented anemia, diarrhoea, depression, agranulocytosis, elevated aminotransferases, generalized dermatitis and severe gingivitis with loss of teeth, prolonged QT interval on ECG, generalized oedema and severe dyspnoea, uroinfection, exacerbation of Crohn’s disease, Campylobacter pylori infection and unacceptable weakness and fatigue. Eight patients received transfusion, 4 patients erythropoietin and 1 granulocyte colony stimulating factor during therapy. No death has been reported. Conclusions: With boceprevir based triple therapy, one of the bests available in 2011–2013 in Hungary, a relevant proportion of hepatitis C infected patients with advanced liver fibrosis achieved sustained viral response. In this cohort, side-effects resembled those reported in registration studies, and resulted in therapy discontinuation with consequent treatment failure in a relevant number of patients. Efficacy and tolerability of boceprevir-based triple therapy are suboptimal, particularly in the most difficult to cure patient population. Orv. Hetil., 2016, 157(34), 1366–1374.