Melanoma subsequent to natalizumab exposure: A report from the RADAR (Research on Adverse Drug events And Reports) program

S1P receptor modulators in Multiple Sclerosis: Detecting a potential skin cancer safety signal

“…In other pharmacovigilance databases, FAERS and Northwestern Medicine Enterprise Data Warehouse (NMEDW), a natalizumabassociated signal for melanoma was proposed. In the "EudraVigilance" database, however, it was not confirmed and in our analysis no signal was detected for Natalizumab for any type of skin cancer (Kelm et al, 2019). Finally in scandinavic nationwide cohort studies, MS patients had generally increased risk of malignant melanomas in a Danish study, while in a Norwegian study malignant melanoma was found in 0.5%, and non-melanoma skin cancers in 1.9% in a total of 637 MS patients (Benjaminsen et al, 2021;Nørgaard et al, 2019), which is higher than expected in the general population.…”

Multiple Sclerosis Disease Modifying Therapy and Cancer risks

“…MS patients that are not exposed to immunosuppressant therapy showed lower incidence of cancer, according with other studies [11]. This increased risk is particularly true for some drugs and some cancers that will be further discussed in separate sections [9,10,12].…”

Multiple Sclerosis Treatment and Melanoma Development

“…The debate on a possible relationship between cutaneous melanoma and MS therapy with natalizumab and/or fingolimod is still open. Since the first two reported cases in 2008 [9], patient reports [6,8,[11][12][13][14][15][16][17][18] and evaluation of clinical trial results [19,21,22] indicate that an association between melanoma development and treatment with these drugs may occur, but the number of cases examined is too low to exclude a mere casualty. In vitro analysis using cell lines and preclinical melanoma animal models did not help in clarifying this aspect since also in these conditions natalizumab or fingolimod act either as protumorigenic or as antitumorigenic molecules.…”

“…Therefore, melanoma occurrence in these patients could be merely a coincidence [20]. Nevertheless, recent studies indicated a statistically significant association of melanoma occurrence with the treatment with those disease modifying drugs [21,22]. Prospective follow-up of MS patients treated with natalizumab evaluated possible modifications of naevi under treatment and found out that either after 14 months [23] or after 4 years [24] the degree of clinical and dermoscopic changes during natalizumab therapy did not differ from the rate of spontaneous evolution of naevi in untreated individuals as reported in the literature.…”