| アブストラクト | A 43-year-old female with multiple sclerosis developed urethral melanoma. The only potential risk factor was treatment with natalizumab, a humanized monoclonal antibody against alpha4 integrins. To investigate the risk-exposure relationship, we reviewed this case, all other published cases, and cases of natalizumab-associated melanoma reported to regulatory agencies. Data sources included the Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) (2004-2014), a FDA Advisory Committee Meeting Report, and peer-reviewed publications. In the United States, the manufacturer maintains an FDA-mandated Tysabri Safety Surveillance Program (part of the Tysabri Outcomes Unified Commitment to Health (TOUCH)) of natalizumab-treated patients. We statistically compared reporting completeness for natalizumab-associated melanoma cases in FAERs for which information was obtained entirely from the TOUCH program versus cases where FAERS information was supplemented by TOUCH program information. FAERS included 137 natalizumab-associated melanoma reports in patients with multiple sclerosis. Median age at melanoma diagnosis was 45 years (range: 21-74 years). Changes in preexisting nevi occurred in 16%, history of cutaneous nevi occurred in 22%, diagnosis within 2 years of beginning natalizumab occurred in 34%, and 74% had primary surgical treatment. Among seven natalizumab-treated MS patients who developed biopsy-confirmed melanoma on treatment and reported in the literature, median age at diagnosis was 41 years (range: 38-48 years); and the melanoma diagnosis occurred following a median of 12 natalizumab doses (range: 1-77 doses). A history of mole or nevi was noted in four patients and a history of prior melanoma was noted in one patient. Completeness scores for reports were significantly lower for FAERS cases reported from the TOUCH program versus FAERS cases supplemented by TOUCH information (median score of 2 vs. 4 items out of 8-possible items, P < 0.0007). Clinicians should monitor existing nevi and maintain suspicion for melanoma developing in natalizumab-treated patients. The TOUCH Safety Surveillance Program, currently focused on progressive multifocal leukoencephalopathy, should be expanded to include information on other serious complications including malignancies, particularly if they are immunologic in nature. |
|---|
| ジャーナル名 | Cancer medicine |
|---|
| Pubmed追加日 | 2017/6/22 |
|---|
| 投稿者 | Sabol, Rachel A; Noxon, Virginia; Sartor, Oliver; Berger, Joseph R; Qureshi, Zaina; Raisch, Dennis W; Norris, LeAnn B; Yarnold, Paul R; Georgantopoulos, Peter; Hrushesky, William J; Bobolts, Laura; Ray, Paul; Lebby, Akida; Kane, Robert C; Bennett, Charles L |
|---|
| 組織名 | Tulane University School of Medicine, New Orleans, Louisiana.;The Southern Network on Adverse Reactions (SONAR) program, University of South;Carolina College of Pharmacy, Columbia, South Carolina.;Department of Neurology, Perelman School of Medicine, Philadelphia, Pennsylvania.;The Arnold School of Public Health, University of South Carolina, Columbia, South;Carolina.;University of New Mexico, College of Pharmacy, Albuquerque, New Mexico.;Oncology Analytics, Plantation, Florida.;The Medical University of South Carolina Hollings Cancer Center, Charleston,;South Carolina.;William Jennings Bryan Dorn Veterans Administration Medical Center, Columbia, |
|---|
| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/28635055/ |
|---|
