Immune reconstitution therapy (IRT) in multiple sclerosis: the rationale

Area of Science:

• Neuroimmunology
• Immunotherapy
• Autoimmune Diseases

Background:

• Multiple sclerosis (MS) and other neuroimmune diseases are rapidly evolving fields for immunotherapy.
• Immunomodulating drugs have seen accelerating inclusion over the past 25 years.
• Current immunotherapies can be categorized by molecular construction and mechanism of action.

Purpose of the Study:

• To compare the efficacy and safety of intermittent (IRT) versus continuous immunotherapy for MS.
• To explore the potential of IRTs to re-induce self-tolerance and achieve long-term remission or a "cure" for MS.
• To analyze the impact of IRTs on the lymphocyte repertoire and compare adverse event profiles with chronic treatments.

Main Methods:

• Classification of immunotherapeutic agents into seven categories.
• Distinction between continuous treatments and intermittent therapies (IRTs) for MS.
• Analysis of long-term outcomes and lymphocyte repertoire changes in patients treated with IRTs like alemtuzumab and HSCT.

Main Results:

• IRTs, such as alemtuzumab and HSCT, have demonstrated long-term remission and no evidence of disease activity (NEDA) in MS patients for over 10 years.
• IRTs induce radical changes in the lymphocyte repertoire post-reconstitution, potentially explaining long-term benefits and self-tolerance re-induction.
• Compared to chronic treatments, IRTs have lower, front-loaded risks of adverse events and higher patient adherence.

Conclusions:

• Intermittent immunotherapy represents a novel concept for MS therapy with substantial advantages over chronic immunosuppression.
• IRT therapies show significantly higher efficacy in MS and may achieve re-induction of disrupted self-tolerance.
• Benefits of IRT include higher treatment adherence and reduced cumulative side effects compared to chronic immunosuppression.