Presenting Author:

Erika Hagstrom

Principal Investigator:

Beatrice Nardone

Department:

Dermatology

Keywords:

melanoma, natalizumab, multiple sclerosis, pharmacovigilance

Location:

Ryan Family Atrium, Robert H. Lurie Medical Research Center

C13 - Clinical

Association of melanoma with natalizumab

Introduction Natalizumab (N) is an α4-integrin inhibitor, approved for the treatment of multiple sclerosis (MS) and Crohn’s disease. Of concern are several reports of malignant melanoma (MM) subsequent to N exposure. Moreover, the current Full Prescribing Information (FPI) for N does not currently list MM as a possible adverse reaction. The aim of this study was to determine if a safety signal was detectable in any of 3 large databases: FAERS (FDA Adverse Event Reporting System), EudraVigilance (EMA) database and the Northwestern Medicine Electronic Data Warehouse (NMEDW) with data from > 8 million individual patients. Methods We searched the FAERS database (January 2004 through June 2014) for terms related to MM combined with N and calculated the Proportional Reporting Ratio (PRR) for detection of a safety signal, defined as number of events >3, chi-square result (>4) and the PRR (>2). We also searched a large, urban, electronic medical record (EMR) data repository (>4 million individuals, January 2004 to December, 2015) for all MS patients who were exposed to N and were subsequently diagnosed with MM (ICD9 codes 172.0-172.9; ICD-10: C43.0-C43.9) > 3 months after N exposure. Finally the EudraVigilance database up to July 2016 was also searched for terms related to MM combined with N. Results A safety signal was detected (PRR: 2.42; 95%CI: 2.10-2.8) based on 205 reports of MM subsequent to N exposure in FAERS. In the NMEDW cohort, of 5,097 MS patients, 192 were exposed to N of which 3 (1.6%) developed MM, representing a significant association (Fisher’s exact test p<0.0001). Finally, 78 reports for MM subsequent to N were detected in the EudraVigilance database; however safety signal was not calculated for this database. Conclusions The findings detected an association between N exposure and subsequent MM in both the NMEDW repository and FAERS, and 78 reports were detected in EudraVigilance from the EMA. Given that the manufacturer’s FPI does not include MM as a possible adverse reaction, further exploration of this serious and important possible association is warranted.