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Immunomodulator (IM) treatments in ulcerative colitis (UC) are not curative and carry increased risk of complications, sometimes leading to therapy changes, reduced treatment benefits, and eventual relapse. We assessed patterns of IM utilization and therapy changes, complications, and disease relapse in a real-world population of patients with moderate-to-severe UC.Claims data from a large commercially insured U.S. population were retrospectively analyzed. Inclusion criteria were (1) ≥2 UC diagnosis claims (ICD-9-CM 556.xx) between January 2005 and July 2010, (2) ≥1 IM claim, where first IM claim defined the index date, (3) ≥12 months preindex health plan enrollment (baseline), and (4) ≥24 months postindex plan enrollment (follow-up). Characteristics of and changes to the index IM therapy during follow-up were descriptively assessed, as were complications and disease relapses.A total of 2136 patients were identified for inclusion (age, mean [SD], 46  years, 54% female). Azathioprine was the most common index IM (46% of patients), followed by 6-mercaptopurine (28%). Switching from the index IM to another therapy class was common (21% of patients), with 5-ASAs (48% of switchers), oral corticosteroids (21%), and biologics (17%) being the most frequent next agents used. Augmentation was also common (25% of patients), with 5-ASA being, by far, the most frequent agent added to the index IM (72% of augmenters). Thirty percent of patients experienced a complication, and 73% of patients relapsed, with the majority of relapses occurring during index IM exposure.This assessment of IM treatments for UC demonstrated frequent changes to therapy and high downstream complication and relapse rates.