Cancer Risk in Patients with Multiple Sclerosis: Potential Impact of Disease-Modifying Drugs.

In the 1990s, the first disease-modifying therapies (DMTs) for multiple sclerosis (MS) were injectable immunomodulatory (IM) drugs, including four different interferon-ß preparations and glatiramer acetate. Since 2000, more than 15 immunosuppressant (IS) drugs have been used, with a more or less specific action on inflammation. These include monoclonal antibodies targeting CTL4, the integrin receptor, the interleukin (IL)-2 receptor, CD19, CD20, CD52, and the sphingosine 1 phosphate family. The association between MS and cancer has long been investigated but has led to conflicting results. No studies have reported an increased risk of cancer after long-term exposure to IM. Several reports suggest an increase in cancer risk among MS patients treated with IS such as mitoxantrone, azathioprine and cyclophosphamide. Because of their action on the immune system, and due to a lack of available long-term data, a special warning of the potential risk of cancer accompanies the use of recent IS such as cladribine, fingolimod, natalizumab or alemtuzumab. In most studies, factors such as diet, smoking, solar radiation, and hormone therapy, all of which influence cancer risk, have not been considered. For fingolimod, natalizumab, alemtuzumab, dimethyl fumarate, teriflunomide, daclizumab and ocrelizumab, risk management plans outlined by regulatory agencies are mandatory. They allow prospective detection of some red flags, in particular those for the increased risk of cancer. We review the current evidence behind the increased risk of malignancy in MS patients receiving DMTs, and provide an overview of the DMTs that are currently in use and those in clinical trials. The known risks and benefits of these therapies will be considered.