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
2016
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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
0
Citations
NaN
KQI