Biologic dose escalation in inflammatory bowel disease in the United States.

backgroundTreatment for inflammatory bowel disease (IBD), composed of Crohn disease (CD) and ulcerative colitis (UC), frequently employs biologics to help control inflammation, reduce symptom burden, and limit disease progression. Because of both the lifelong, progressive nature of disease and potential for loss of therapy response over time, therapy changes are common. Biologic dose escalation is one method to adjust therapy regimens following loss of response.

objectiveTo assess the occurrence of dose escalation in CD and UC and its influence on health care costs.

methodsAdults with a diagnosis of CD or UC newly initiating therapy with a biologic (adalimumab, infliximab, ustekinumab, vedolizumab, or tofacitinib [UC only]) from January 1, 2017, to June 30, 2022, were selected in the Merative MarketScan Commercial and Medicare Databases. The first claim for the biologic served as the index date and patients were followed over a 12-month pre-period and a 12-month-or-longer post-period. Dose escalation during the maintenance phase of therapy, discontinuation, and postdiscontinuation switching were assessed in biologic-based subgroups in each of the CD and UC cohorts; per-patient-per-month (PPPM) IBD-related health care costs over the duration of index biologic treatment were also calculated.

resultsAnalyses included 6,056 patients with CD (33.5% adalimumab, 30.6% ustekinumab, 18.8% infliximab, 17.1% vedolizumab) and 4,533 patients with UC (35.1% vedolizumab, 30.6% adalimumab, 16.8% infliximab, 10.0% ustekinumab, 7.5% tofacitinib). Dose escalation occurred in 30.4% of patients with CD (adalimumab 20.8%, infliximab 48.8%, ustekinumab 26.9%, vedolizumab 36.2%) and 30.1% of patients with UC (adalimumab 23.0%, infliximab 44.8%, ustekinumab 25.5%, vedolizumab 31.8%, tofacitinib 24.9%). Patients with evidence of dose escalation had lower rates of discontinuation compared with nonescalators over follow-up but were more likely to switch biologics after discontinuation. PPPM IBD-related health care costs over the course of treatment were substantial and largely driven by index biologic costs. Mean PPPM costs for the CD cohort ranged from $4,543 in the infliximab group to $14,031 in the ustekinumab group; costs were similar in the UC cohort, ranging from $5,213 in the infliximab group to $14,246 in the ustekinumab group. Within both cohorts, dose escalation was a significant predictor of increased IBD-related health care costs.

conclusionsNearly one-third of patients with IBD in this study escalated their biologic dose, which significantly increased their disease-related health care costs. These results demonstrate current challenges in long-term biologic therapy in IBD and highlight the ongoing need for further research into biologic management strategies to optimize IBD patient care and long-term outcomes, while containing costs.