The first part of this chapter covers some general aspects of immunotherapy. In the second part, the mechanisms and side effects of the most widely used immunosuppressive and immunomodulatory agents are reviewed. The final part provides a brief overview of the most promising future strategies and therapeutic developments.
Principles of immunotherapy
Practical issues and general rules
Commencing with the trials of corticosteroids for treatment of rheumatoid arthritis in the late 1940s, numerous agents have been employed in many diseases with suspected or established autoimmune pathogenesis to abrogate excessive immunoreactivity. Unfortunately, the lack of specificity of these agents and their concurrent toxicities have limited their effectiveness. However, many formerly fatal or intractable diseases characterized by aberrant immunity can now be considered responsive to manipulation of the underlying defects in immune regulation. When making the decision to employ one of these agents, one should know as much as possible about the nature of the immune abnormality to be corrected and of the ability of a given drug to influence this process. Furthermore, the adverse effects of the agent should be weighed against the possible benefits (Machkhas et al., 1997).
The goals of treatment seem simple enough: to improve clinical deficits and to stop or slow progression of the disease process while keeping side effects to a minimum. Before initiation of any form of immunotherapy, and during therapy, a number of important points need to be considered and checked (Table 93.1). The diagnosis should be unequivocally established. Baseline variables (such as muscle strength, vital capacity, walking distance, etc.) should be documented so they may be measured on follow-up examinations to help in quantifying improvement. Certain medical conditions (e.g. chronic or undiagnosed infections, diabetes) must also be considered. Another major consideration before initiation of therapy is patient compliance. Usually, the risks associated with non-compliance outweigh the benefits of treatment, and non-compliance is a contraindication of immunosuppression. Regarding the duration of therapy, it is important that adequate dosages are given over a sufficient period of time. Otherwise, the agent is terminated prematurely and labelled a ‘treatment failure’, and will probably never be used again, even though in retrospect it is felt that incorrect dosages or insufficient duration of treatment were used.