Refractory disease in autoimmune diseases

Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It can be related to inadequate or inefficacious treatment or to pathogenesis. RD definition has multiple implications to clinical guidelines and to the use of off-label drugs. It should not be regarded as lost cases and prospective studies, registries and clinical trials should be planned.