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

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.