QT-prolonging effects of monoclonal antibody drugs in humans: a systematic review of two literature and a public adverse event database.

Unlabelled: Drug-induced prolongation of the electrocardiogram QT interval, a risk factor for ventricular arrhythmia and death, has been observed for some small drugs with masses < 1 kDa. Over the last two decades, patient exposure to large molecule monoclonal antibody drugs with masses > 40 kDa has increased dramatically; hence, the aim of this study was to systematically review the scientific literature for evidence of QT prolongation induced by these drugs.

Methods: The PubMed and Embase databases were searched for cases indicative of drug-induced QT prolongation for 28 pre-identified monoclonal antibody drugs authorized in Europe. Cases were identified by applying a standardized search string and a subsequent text search and manual review. In parallel, the public European Medicines Agency (EMA) database was searched for reported frequencies of adverse events indicative of QT prolongation.

Results: A valid case of drug-induced QT prolongation, caused indirectly by hypocalcaemia, could be identified for only 1 out of 28 monoclonal antibody drugs (denosumab) from the PubMed and Embase search. The EMA database showed no hits for denosumab. Considering that hypocalcaemia-mediated QT prolongation is an already-identified and labelled risk for denosumab, the current study did not identify any additional evidence of QT prolongation caused by monoclonal antibody drugs.