The annual cost of ulcerative colitis (UC) in the US is estimated to be as high as $14.9 billion, of which therapeutics account for up to 45%. The mean annual drug cost per patient with moderate to severe UC is $28,586. However, only 49% of patients achieve endoscopic healing on their first anti-tumor necrosis factor (anti-TNF) therapy and up to half of UC patients on biologics discontinue therapy within 12 months of initiation which leads to high rates of hospitalization and surgery. We performed a health care payer budget impact analysis to assess the influence of a precision medicine RNA-based classifier (PrismUC) that predicts, at baseline, anti-TNF non-response in patients with moderate to severe UC.