Prodromal signs and symptoms of serious infections with tocilizumab treatment for rheumatoid arthritis: Text mining of the Japanese postmarketing adverse event-reporting database

<p><b>Objective:</b> To search for signs and symptoms before serious infection (SI) occurs in tocilizumab (TCZ)-treated rheumatoid arthritis (RA) patients.</p> <p><b>Methods:</b> Individual case safety reports, including structured (age, sex, adverse event [AE]) and unstructured (clinical narratives) data, were analyzed by automated text mining from a Japanese post-marketing AE-reporting database (16 April 2008–10 April 2015) assuming the following: treated in Japan; TCZ RA treatment; ≥1 SI; unable to exclude causality between TCZ and SIs.</p> <p><b>Results:</b> The database included 7653 RA patients; 1221 reports met four criteria, encompassing 1591 SIs. Frequent SIs were pneumonia (15.9%), cellulitis (9.9%), and sepsis (5.0%). Reports for 782 patients included SI onset date; 60.7% of patients had signs/symptoms ≤28 days before SI diagnosis, 32.7% had signs/symptoms with date unidentified, 1.7% were asymptomatic, and 4.9% had unknown signs/symptoms. The most frequent signs/symptoms were for skin (swelling and pain) and respiratory (cough and pyrexia) infections. Among 68 patients who had normal laboratory results for C-reactive protein, body temperature, and white blood cell count, 94.1% had signs or symptoms of infection.</p> <p><b>Conclusion:</b> This study identified prodromal signs and symptoms of SIs in RA patients receiving TCZ. Data mining clinical narratives from post-marketing AE databases may be beneficial in characterizing SIs.</p