Abstract
Following inadequate response, loss of response, or intolerance to a first-line biologic, patients with Crohn’s disease (CD) may switch treatment to a second-line biologic therapy. Data on the clinical outcomes of patients receiving two or more lines of biologic therapy are limited. We assessed the adverse clinical outcomes of patients with CD receiving different biologic treatment sequences.
ROTARY (Real-wOrld ouTcomes Across tReatment sequences in inflammatorY bowel disease patients) part B used data from the Optum Clinical Database and included adult patients diagnosed with CD who received at least two biologics successively between January 1, 2013 and February 29, 2020. This retrospective cohort study measured adverse clinical outcomes, including the incidences of inflammatory bowel disease (IBD)-related hospitalization, IBD-related surgery, dysplasia, colorectal cancer (CRC), and infection during each line of therapy individually and for both lines of treatment overall. The start of the first line of therapy (LOT1) was defined as the date of first prescription or infusion of a biologic therapy. The start of the second line of therapy (LOT2) was defined as the first date of prescription or infusion of a second-line biologic therapy. LOT1 biologics included in the analysis were adalimumab (ADA), infliximab (IFX), ustekinumab (UST) and vedolizumab (VDZ). LOT2 biologics included were IFX and ADA.
Among all treatment sequences UST to IFX had the highest overall incidences of hospitalization, surgery, CRC, and infection. The overall incidences of hospitalization, surgery, and CRC were lowest for the VDZ to ADA treatment sequence. The overall incidences of infection and dysplasia were lowest for UST to ADA and UST to IFX, respectively; the second-lowest overall incidences for these outcomes were for VDZ to ADA (Figure 1). When comparing adverse clinical outcomes during LOT2, there were similar incidences of hospitalization, surgery, dysplasia, and infection with ADA following either VDZ or UST. In comparison, UST to IFX had higher incidences of hospitalization, surgery, and infection compared with VDZ to IFX (Table 1).
We identified that the VDZ to ADA biologic treatment sequence had the lowest real-world incidences of adverse clinical outcomes in patients with CD. In patients who were unsuccessfully treated with either VDZ or UST during LOT1, ADA was associated with a lower incidence of adverse clinical outcomes during LOT2 than IFX. The adverse clinical outcomes for sequences including two anti-tumor necrosis factor therapies (ADA to IFX, IFX to ADA) were similar during LOT1, LOT2, and overall. These results, although they may be influenced by selection bias, provide potential guidance to clinicians choosing sequences of biologic treatments in patients with CD.
Table 1. Incidence of Adverse Clinical Outcomes During LOT1 and LOT2 in Patients With CD
Figure 1. Overall Incidence of Adverse Clinical Outcomes During Both LOT1 and LOT2 in Patients With CD
