Systematic Literature Review of Real-World Evidence on Dose Escalation and Treatment Switching in Ulcerative Colitis

Abstract

Background Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response, leading to dose escalation or treatment switching. Objective We sought to identify real-world evidence on dose escalation and treatment switching and associated clinical and economic outcomes among adults with ulcerative colitis treated with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib. Methods We conducted a systematic search of Embase, MEDLINE (up to 26 August 2020), and conference proceedings (2017−2020) for studies in adults with ulcerative colitis to assess clinical response and remission, colectomy, adverse events, and economic outcomes related to dose escalation and treatment switching. Results In 56 studies, dose escalation and treatment switching involving infliximab and/or adalimumab were most frequently investigated. Rates of clinical response after dose escalation were 20–95% (1.8–36 months), clinical remission rates were 10–94% (1.8–36 months), colectomy rates were 0–33% (12–38 months), and adverse event rates were 0–18%. Treatment switching rates in 21 studies were 4–70% over 3–62 months, with switch due to loss of response rates of 4–35% over 12–62 months (7 studies). Up to 35% of patients underwent colectomy 12−120 weeks after switching, and 13–38% experienced adverse events. Data relating to economic outcomes were limited to tumor necrosis factor inhibitors, but demonstrated increased direct costs associated with both dose escalation and treatment switching. Conclusion Dose escalation and treatment switching are common with existing therapies. However, clinical response and remission rates vary, and a proportion of patients fail to achieve optimal clinical and economic outcomes. This highlights the need for more efficacious and durable treatments for patients with moderate-to-severe ulcerative colitis.