Center for HIV and Hepatogastroenterology, Duesseldorf, Germany. firstname.lastname@example.org.
In clinical trials with telaprevir (TLV) and boceprevir (BOC) renal impairment was not reported as a relevant adverse event. The PAN study is a non-interventional study enrolling patients treated with peginterferon alfa-2a/ribavirin (PEG/RBV) with or without TVL or BOC. Here we restrict the analysis to hepatitis C virus genotype 1 patients having completed 12 (n=895) or 24 weeks (n=591) of treatment. For estimation of glomerular filtration rate (eGFR) the CKD-EPI formula was chosen. Patients on TLV 38/575 (6.6%) and BOC 10/211 (4.7%) experienced more frequently a decrease in eGFR to <60 mL/min compared to patients on PEG/RBV 1/109 (0.9%) (p<0.05). Risk factors associated with eGFR <60 ml/min in multiple logistic regression analysis were age (p<0.001), arterial hypertension (p<0.05), higher serum creatinine at baseline (p<0.001) and being on triple therapy with TLV or BOC (p<0.01). Patients with an eGFR of <60 ml/min had a lower absolute mean haemoglobin at week 12 compared to patients with an eGFR >60 ml/min (9.7 g/dL ± 1.4 g/dL versus 11.0 g/dL ± 1.7 g/dL) (p<0.001). Most patients on TLV with a decrease of eGFR <60 ml/min showed a marked improvement in renal function after discontinuation of TLV. Conclusion:Renal impairment has not been reported as safety signal in clinical trials with TVL or BOC. However in this large cohort including patients with risk factors for renal impairment a marked decline in renal function was observed in about 5% of patients on triple therapy. In addition to being a safety concern as such, substantial ribavirin dose reductions have to be considered in these patients as anaemia was more pronounced in patients with impaired renal function. Dual treatment of chronic hepatitis C with pegylated interferon alfa and ribavirin is characterised by numerous adverse events. However renal impairment has not been identified as part of the adverse event profile. Until recently, experience with telaprevir (TLV) and boceprevir (BOC) was based exclusively on clinical trials in selected patients. In these trials renal impairment was not reported as a safety issue (1,2,3,4). However, in the French early access program cases of renal failure were observed (5). In the present study we analyzed the development of estimated glomerular filtration rate in patients treated with interferon based therapies with or without the addition of boceprevir or telaprevir in a large cohort of patients enrolled in a non-interventional study.