Background: Sunitinib and sorafenib can induce serious adverse drug reactions (ADR) such as hypothyroidism. However, the incidence has not been reliably determined in clinical trials.
Aims: To determine incidence rates (IR) and hazard ratios (HR) of thyroid hormone (TH) therapy as a surrogate for sunitinib- and sorafenib-induced clinical hypothyroidism.
Methods: A cohort study was performed using claims data for prescriptions covering >80% of German pharmacies. Patients with a first prescription of sunitinib or sorafenib in the period between June 2006 and December 2007 were followed until incident prescription of any TH (event of interest) or censoring (due to loss to follow-up, discontinuation or switch of therapy, prescription of antithyroid drugs or the end of the study).
Results: One-hundred and seventy eight of 1295 sunitinib patients (13.7%) versus 77 of 1214 sorafenib patients (6.3%) received a TH. IR were 24.2 and 12.1 per 100 person-years, respectively. Unadjusted HR for TH therapy was 2.0 (95%confidence interval (CI) 1.5-2.6) for sunitinib compared to sorafenib and remained significant after adjustment for covariates, i.e. type of prescriber, region, insurance status, type of insurance fund, and relevant co-medication.
Conclusions: Sunitinib- and sorafenib-induced hypothyroidism is a more frequent ADR than currently labelled. Furthermore, patients treated with sunitinib have a two-fold increased risk of requiring TH therapy compared to sorafenib. Patients being treated with sunitinib or sorafenib are, therefore, at risk of thyroid function disturbances and routine monitoring both at baseline and throughout treatment with sunitinib and sorafenib is justified.
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