Background: Natalizumab is an effective immunosuppressive therapy for multiple sclerosis (MS) that received its initial FDA approval in 2004. Its most notable toxicity is progressive multifocal leukoencephalopathy (PML), an opportunistic infection that is the focus of an FDA-mandated registry, TOUCH. The Southern Network on Adverse Reactions identified a fatal case of natalizumab-associated urethral melanoma and undertook an extensive evaluation of all cases of natalizumab-associated melanoma included in the FDA’s Adverse Event Reporting System (FAERS) (between 2005 and 2014).
Methods: Patient characteristics were determined from the FAERS reports and put into a comprehensive dataset. The quality of these reports was assessed based on a 15-point scale of various clinical, demographic, and pharmacy components. Cases were identified as being reported through the TOUCH system, using TOUCH information but reporting outside the system, not using TOUCH at all in the U.S. or not U.S. Quality scores and their components within the 4 Touch groups were statistically compared across all attributes using the mathematical programming-based statistical methodology univariate optimal discriminant analysis.
Results: The mean patient age at the time of diagnosis of melanoma was 46 years (SD 11). Seventeen patients were diagnosed with cutaneous melanoma developing in nonsun-exposed areas. We found that cases reported through the TOUCH registry were of lower quality (mean score 7.7) compared with others that reported outside of the U.S. (mean score 8.5, P < .008). Those cases reported through the TOUCH system were less likely to report the site of melanoma (P < .019) and have overall lower clinical scores (P < .04) compared with reports using TOUCH information but reporting outside of the system.
Conclusions: Our findings suggest that in the U.S., the TOUCH Registry should be expanded to require clinicians to report details of natalizumab-associated melanoma, an opportunistic illness that frequently develops in immunocompromised persons. Also, the FDA-approved product label for natalizumab should be revised to include information on occurrences of melanoma among natalizumab-treated MS patients, particularly those who have cutaneous nevi prior to natalizumab initiation. Natalizumab-treated MS patients and their physicians should be vigilant for changes in nevi appearances and development of new cutaneous lesions (particularly in nonsun-exposed cutaneous areas).
