The current landscape and unmet needs in multiple sclerosis.
When introduced in the early and middle 1990s, current first-line pharmacologic therapies for multiple sclerosis (MS)--interferon beta-1a, interferon beta-1b, and glatiramer acetate--constituted a major advancement in MS treatment. Nevertheless, disease progression, although typically delayed with these agents, remains inevitable in most patients and constitutes a significant limitation of the currently available treatments. Moreover, the first-line therapies all require frequent subcutaneous or intramuscular injections, delivery modalities that are associated with subpar treatment adherence. The demand for more effective agents has produced a new generation of MS therapies with impressive efficacy profiles--although their long-term safety and tolerability remain largely unknown. Some of the new agents have been formulated for oral administration, which will likely have a positive impact on treatment adherence. These new agents are appearing during a time of major change in MS research. As the old expectation of inevitable disease progression is being reconsidered, the notion of sustained disease inactivity has become a credible, still somewhat elusive, goal. Neuroprotection may also be possible with new and existing treatments. At the same time, new imaging techniques, such as measuring disease progression via T1-hypointense lesions ("black holes"), and a better understanding of pathophysiologic factors in MS--such as the role of neurotrophic growth factors and oxidative stress--are changing the ways that efficacy is measured and how new agents are developed.
Markowitz
Clyde E
CE
Multiple Sclerosis Center, University of Pennsylvania, 3400 Spruce St, 3 W Gates Bldg, Philadelphia, PA 19104, USA. cmarkowi@mail.med.upenn.edu
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004333:Drug Administration Routes; D000068717:Glatiramer Acetate; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy*; D000069442:Natalizumab; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010455:Peptides / Q000627:therapeutic use; D012074:Remission Induction
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D018696:Neuroprotective Agents; D010455:Peptides; D000068576:Interferon beta-1b; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D000068556:Interferon beta-1a