In the last few years impressive research and development programs for drug treatments in multiple sclerosis (MS) have been developed. Based on the understanding that MS is a chronic inflammatory disorder of the central nervous system, traditionally considered to be an autoimmune, demyelinating disease, therapeutic strategies have been directed at immune modulation and inflammation control.
At present, there are several options to treat MS, both licensed first-line disease-modifying drugs (DMDs) and second-line treatments. Currently available first-line MS therapies have shown significant efficacy throughout many trials, but they may produce different side effects. Despite DMDs being well known and safe, they require regular and frequent parenteral administration and are associated with limited long-term treatment adherence. Moreover, DMDs are only partially effective in halting MS relapses and, in particular, disability progression if they are not administered in the early stage of the disease. In this issue Drs. Cruce and Freedman focus on the treatment effect size for DMDs, which seems to be larger when these therapies are given in patients with clinically isolated syndrome than when they are given in patients with relapsing remitting MS. The authors also stress the importance of long-term follow-up studies, which offer valuable insight regarding the dynamics of MS pathology and response to current and new treatment approaches.
Given the limitations of current DMD interventions, management of MS has been significantly improved by more recently developed second-line treatments, which include monoclonal antibodies and new oral agents that showed greater efficacy and probably better patient compliance compared with the injectables, but they may also carry novel safety and tolerability concerns. Neurologists are starting to use more-powerful but potentially dangerous drugs in the treatment of MS. Safety is likely to become the most important factor in the future development of MS drugs. Drs. Comabella and Montalban focus in their review on the increasing new options in the treatment of MS, emphasizing the necessity of a more personalized approach for the management of MS patients. The most challenging aspect for neurologists will be making their patients understand the need for balancing in each case, the pros and cons of new treatments, and how serious side effects may outweigh benefits in certain individuals. This is particularly important given the lack of long-term safety data with these new treatments versus currently approved DMD therapies.
A number of potential therapies for MS are also in late-stage development. New and novel therapeutic agents are being trialed in MS centers worldwide. These include not only oral agents for relapsing and progressive forms of the disease but also new monoclonal antibodies. New drugs for MS need to be placed within this evolving marketplace in which the ease of delivery together with efficacy and side effects need to be balanced against the known issues as well as the known long-term safety of standard injectables.
The final decision to use these new therapies will most likely be based on an overall assessment of efficacy, safety, tolerability and adherence, the potential need for monitoring, and cost effectiveness.