- An adverse prognosis, documented by persistent signs and symptoms of CD that have failed to respond satisfactorily to medical and surgical therapies in the past, including but not limited to systemic immune suppressive drugs and biopharmaceuticals; to be considered as refractory to medical and surgical therapy, there must be clinical, endoscopic, and histologic evidence of active inflammatory Crohn's Disease that has either persisted or recurred despite exhaustive treatment with available pharmaceutical and surgical therapies; exhaustive treatment is defined as prior exposure to the following, without durable improvement: