Multiple faces of multiple sclerosis in the era of highly efficient treatment modalities: Lymphopenia and switching treatment options challenges daily practice.

The expanded treatment landscape in relapsing-remitting multiple sclerosis (MS) has resulted in highly effective treatment options and complexity in managing disease- or drug-related events during disease progression. Proper decision-making requires thorough knowledge of the immunobiology of MS itself and an understanding of the main principles behind the mechanisms that lead to secondary autoimmunity affecting organs other than the central nervous system as well as opportunistic infections. The immune system is highly adapted to both environmental and disease-modifying agents. Immune reconstitution following cell depletion or cell entrapment therapies eliminates pathogenic aspects of the disease but can also lead to distorted immune responses with harmful effects. Atypical relapses occur with second-line treatments or after their discontinuation and require appropriate clinical decisions. Lymphopenia is a result of the mechanism of action of many drugs used to treat MS. However, persistent lymphopenia and cell-specific lymphopenia could result in disease exacerbation, secondary autoimmunity, or the emergence of opportunistic infections. Clinicians treating patients with MS should be aware of the multiple faces of MS under novel, efficient treatment modalities and understand the intricate brain-immune cell interactions in the context of an altered immune system. MS relapses and disease progression still occur despite the current treatment modalities and are mediated either by failure to control effector mechanisms inherent to MS pathophysiology or by new drug-related mechanisms. The multiple faces of MS due to the highly adapted immune system of patients impose the need for appropriate switching therapies that safeguard disease remission and further clinical improvement.