Patterns of Treatment With Biologics in Patients With Crohn Disease

A real-world, retrospective study assessed treatment patterns of typically prescribed biologic drugs for Crohn disease (CD) over the course of 3 years, using an all-payer claims database representing 80% of the US health care system. More patients received infliximab, adalimumab, and vedolizumab than ustekinumab, the most recent to be approved. However, the study found ustekinumab had the highest persistence rate and lowest dose escalation rate of the 4 biologics in patients with CD.

Conventional treatments for moderate-to-severe Crohn disease (CD), 1 type of inflammatory bowel disease (IBD), include corticosteroids and immunomodulators. However, the authors noted that 20% to 40% of patients do not respond to these treatments. Biologics are recommended for those who either do not respond, experience loss of response, or are intolerant of conventional treatments.

Biologics approved in the US for treating CD include the tumor necrosis factor (TNF) alpha inhibitors infliximab and adalimumab, the anti-integrin biologics certolizumab pegol and natalizumab, and ustekinumab, a monoclonal antibody targeting interleukin (IL)-12 and IL-23, which was approved in 2016. Risankizumab, a monoclonal antibody specific to IL-23, was approved in 2022. The FDA has approved biosimilars referencing infliximab, adalimumab, and ustekinumab, and certolizumab pegol and vedolizumab biosimilars are currently in the pipeline.

According to the authors, there is limited real-world evidence on long-term treatment patterns and dose titration following initiation of biologics in patients with CD. They said previous real-world studies either did not report rates of dose escalation or dose titration for individual biologics or had shorter follow-up durations. Their study described drug persistence, adherence, and dose titration in patients with CD over 3 years of follow-up using the STATinMED RWD Insights all-payer medical and pharmacy database.

The study included adult patients with confirmed CD and three years of follow-up data following the first claim for a biologic between September 2016 and October 2018. Of 2309 total patients, 847 (37%) were treated with the infliximab reference product, 72 (3%) with an infliximab biosimilar, 486 (21%) with vedolizumab, 394 (17%) with ustekinumab, and 85 (3.7%) with certolizumab pegol. Because of the small sample sizes, the authors excluded certolizumab pegol and infliximab biosimilars from their analyses.

Common comorbidities in patients with CD included anemia, anxiety, depression, and hypertension. More patients who were prescribed ustekinumab had comorbidities compared to those receiving vedolizumab, adalimumab, or infliximab, as reflected by a higher baseline Charlson Comorbidity Index score and baseline prevalence of individual comorbidities.

Among the biologics, drug persistence over 3 years was highest for ustekinumab (61%), followed by vedolizumab (58%), adalimumab (52%), and infliximab (48%). Overall switches were highest in patients originally prescribed infliximab (33%), followed by adalimumab (25%), and ustekinumab (19%). A total of 115 patients originally prescribed reference infliximab (14%) switched to an infliximab biosimilar over the 3-year follow-up.

Twenty-four percent of patients originally prescribed infliximab, 24% of those originally prescribed adalimumab, 23% of those prescribed ustekinumab, and 22% of those prescribed vedolizumab discontinued and then later restarted the same biologic.

The rate of discontinuation of (without a switch to another biologic or later restart) was highest for adalimumab, with 37% of patients discontinuing treatment. Thirty-one percent of patients taking ustekinumab, 28% of those taking infliximab, and 25% of those taking vedolizumab discontinued treatment.

The dose titration rate ranged from a high of 77% for patients prescribed infliximab to a low of 51% for those prescribed ustekinumab. Among patients prescribed vedolizumab, 68% underwent dose titration as well as 53% of those prescribed adalimumab. Among all patients undergoing dose titration, dose reduction occurred most often with ustekinumab (17%) and dose escalation occurred most often with infliximab (66%).

Patients with CD receiving ustekinumab had a higher persistence and lower dose escalation rate over 3 years compared to more established biologics adalimumab, infliximab, and vedolizumab. The authors commented this possibly suggests a better clinical response to ustekinumab compared to other biologics in CD. They added, “future studies with longer follow-up adjusting for confounders are needed to better understand treatment patterns among biologics users.”

Reference

Zhao R, Ding Z, Gupta P, et al. Evaluation of treatment patterns and maintenance dose titration among patients with Crohn's disease initiating biologics with 3 years of follow-up. J Health Econ Outcomes Res. 2023;10(2):111-120. doi:10.36469/001c.88947