The ideal of every patient and physician is to identify a diagnosis whose natural history is self-limited, or if not, a diagnosis for which an effective treatment can be administered. Autoimmunity is believed to be the contributing, if not causal, mechanism of a significant number of neuromuscular disorders.1 Accordingly, patients with proven or suspected autoimmune neuromuscular disorders become candidates for treatments that modulate or suppress immune-mediated nerve, neuromuscular junction, or muscle dysfunction or injury. Familiarity with drugs or other interventions that suppress or modulate the patient's immune system is therefore a prerequisite for anyone practicing neuromuscular medicine.
In this book, we will define immunomodulation as any therapy that affects in any way the native activities of a patient's immune system in an attempt to mitigate disease. We will define immunosuppression as a subcategory of immunomodulation in which a patient's immunologic response is impaired by one of the three recognized mechanisms.2,3 One mechanism, as occurs with drugs such as azathioprine, cyclophosphamide, mycophenolate, and methotrexate, curtails B-cell and T-cell proliferation by cell cycle interruption. Another mechanism, as exemplified by drugs such as the calcineurin inhibitors (e.g., cyclosporine and tacrolimus) and corticosteroids, is impairment of T-cell activation. A final mechanism of immunosuppression is accomplished by monoclonal antibodies–directed cell surface antigens, rituximab being the most notable example. Conversely, we will consider interventions such as intravenous immunoglobulin (IVIg) or plasma exchange (PLEX) to be immunomodulating, not immunosuppressive.
The authors strongly endorse the concept of evidence-based medicine. At the same time, we recognize that evidence-based medicine applies to populations and that strict adherence to evidence guidance is not always in the best interests of the individual patients we are responsible for. In neuromuscular medicine, there are numerous examples of treatments that are universally considered to be efficacious yet remain of unproven benefit by "evidence-based" standards.4 Corticosteroids in myasthenia gravis (MG) is one notable example, discovered by innovative effort by individual clinicians. Because of the accepted efficacy of this and other historically identified empiric treatments, it is unlikely that a number of currently accepted treatments will ever be validated by large prospective studies.
Our position is also supported by personal witness of unequivocal benefit to individual patients, who respond to treatments demonstrated to be ineffective to larger populations with the same disease. Rituximab in MuSK-positive MG is such an example.5 Accordingly, this chapter will describe, and in some cases endorse, the off-label uses of immunomodulating treatments for various neuromuscular diseases even in the absence of evidence-based support. We do so cautiously as we recognize that these idiosyncratic responses may be harmful as well as helpful. Ultimately, each physician needs, along with their patient, to determine whether the potential benefits of immunomodulating treatment, of proven or unproven benefit, exceed the probability and magnitude of potential risk.
This chapter will approach immunomodulating treatment of presumed immune-mediated disorders by focusing on the treatments, ...