Publications

Salgado and colleagues conducted a systematic literature review of the safety profiles of protein kinase inhibitors (PKis) used for the treatment of rheumatoid arthritis (RA). Additionally, the study aims included identification of any class and molecule-related target and off-target adverse events. Data from 11,858 patients across 41 publications (phase 2 and 3 studies and two pooled analyses) were analysed. As well as published trials of PKi in RA, studies on healthy individuals and patients with diseases with similar comorbidity burden were looked at. The analysis found that PKis have a unique safety profile due to off-target inhibition of kinases as well as specific target-related adverse events, some of which were of particular note, and some of which were dose related. Dizziness was more frequent in patients treated with pamapimod than the comparator group; dose-related hypercholesterolaemia was more common with tofacitinib than comparator, and neutropoenia and hypertransaminasemia were more common with fostamatinib than in controls.The c-Kit inhibitors imatinib and masitinib gave higher incidences of several adverse events (oedema, nausea, vomiting and diarrhoea) than in controls suggesting a family-related adverse event (AE) profile owing to altered gastrointestinal function. Serious malignancies and infections were not significantly more frequent in PKi-treated patients than in comparator groups, including those receiving biologic agents. This analysis may help inform the choice of PKi or other biologic for safer treatment of patients