Rationale and risks of novel immunomodulatory therapies in rheumatoid arthritis

The need for new therapies for the treatment of rheumatoid arthritis (RA) has arisen during an era where clinicians have realized that RA is a far more ominous condition than was thought previously. The last decade has revealed numerous studies depicting the limited long-term efficacy and tolerability of conventional disease-modifying antirheumatic drug (DMARD) therapies. Moreover, DMARDs have not been shown to be truly capable of modifying articular, functional and radiographic outcomes in patients with RA. These issues have been raised amidst significant advances in our understanding of the immunopathogenesis of RA and advances in biotechnology. Such advances have led to a revised approach to using conventional DMARDs, while new pharmacologic and biospecific interventions are being developed. This chapter will discuss the clinical and biologic rationale for novel therapies for patients with RA and the hazards imposed by the therapeutic manipulation of various immune effector mechanisms n patients with RA.