Therapeutic resistance in autoimmune diseases

We are living in new times in medicine: New therapeutic strategies point to early intervention in many autoimmune diseases and, over time, frequent changes in drugs in the absence of response to clearly defined clinical and biological targets. In addition, with the emergence of new drugs, better definitions are needed in trials in order to avoid misclassification as ‘‘therapeutic resistant’’ (TR). But what really is TR in autoimmune diseases? Is it the same as refractory disease? What are the causes of TR? Can we prevent or overcome it? TR means inefficacy of treatment. However, first it is important to clearly define the targets set with a specific treatment. Several other premises must also be confirmed before assuming it (Table 1). Patient drug intolerability does not necessarily lead to a TR definition. When the therapeutic target is not achieved, the diagnosis should be revised and occult disease should be pursued. For example, a patient with cerebral small vessel thrombosis (personal experience) was diagnosed with antiphospholipid syndrome (APS) and continued to have cerebral thrombotic events and worsened migraine on adequate anticoagulation. The brain magnetic resonance imaging (MRI) and genetic test later confirmed cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) disease, and the small vessel disease was not due to APS. Another patient with pulmonary arterial hypertension related to anticentromere scleroderma 1 worsened with calcium antagonists because of occult pulmonary venoocclusive disease. Another example is the over diagnosis of Evans Syndrome and its lack of response to classic treatment when the thrombocytopenia and autoimmune hemolytic anemia are from different