Benefit-Risk of Immunomodulators in Multiple Sclerosis. Alemtuzumab and Next?

Abstract

End of December 2013, alemtuzumab, a monoclonal antibody for multiple sclerosis (MS) with an immunomodulator action targeting CD52 receptors and inducing decrease counts of lymphocytes B and T was rejected by the Food and Drug Administration, as the registration dossier had not shown convincing evidence that the benefit of the drug would overreach its safety risks. The question is in fact more global as immunomodulators constitute the majority of the newly registered drugs and drugs in clinical development for MS. The knowledge accumulated by the time these drugs are registered does not suffice to ascertain their safety profile. This is preoccupying as these treatments are intended to be administered to young patients who need to be treated for decades. Cumulative risks over years with such treatments are at the moment unknown but are certainly non negligible. Despite significant benefits of immunomodulation in the treatment of MS, the solution for treatment of disorders with auto-immune origin is likely to come from targeting more specific factors to avoid long-term depression of the immune system. Research and development in this direction need to be actively encouraged.