Almost one-third of people followed in an inflammatory bowel disease registry stopped biologic therapy within 1.5 years, most often due to loss of response.

The findings highlight the real-world impact of biologic discontinuation on IBD care and the importance of optimizing therapy to avoid loss of response, according to Edward L. Barnes, MD, MPH, an assistant professor of gastroenterology and hepatology at the University of North Carolina at Chapel Hill.

“Secondary loss of response, particularly due to antibody formation, remains a critical issue in the long-term effectiveness and durability of biologic therapy for the treatment of Crohn’s disease and ulcerative colitis,” Dr. Barnes said.

To better understand the factors associated with discontinuation of biologic agents in a real-world cohort, Dr. Barnes and his colleagues analyzed data on 856 IBD patients (39% with ulcerative colitis, 61% with Crohn’s disease) who received care at 34 community and academic practices across the United States. These patients were enrolled in the TARGET-IBD observational registry between July 2017 and August 2020, and began treatment with a biologic therapy during the study period.

Overall, more than 30% of patients stopped treatment within 18 months (median time to discontinuation, 10 months). Discontinuation of treatment was somewhat more common with anti–tumor necrosis factor agents than anti-integrin and interleukin (IL)-12/IL-23 inhibitor therapies, the researchers found.

Loss of response to treatment was the most common reason for discontinuation (31%), followed by side effects (23%) and initial lack of response during induction therapy (primary nonresponse; 21%).

Dr. Barnes noted that development of drug antibodies led to treatment discontinuation in 10% of patients. “Given that secondary loss of response is often due to factors such as antibody formation, there should be a continued focus on optimizing therapy,” he said.

Strategies for optimizing biologic therapy, he said, can include:

• combination therapy when appropriate;
• assessment of drug and antibody levels when loss of response is suspected, followed by dose optimization or combination therapy; and
• personalized approaches to treatment choices or regimens.

“Additionally, I think addressing expectations of therapy with patients will always be critical, including time to expected effectiveness or clinical response, potential adverse effects, and factors that would necessitate discontinuation of therapy,” Dr. Barnes said.

Given that almost one-third of patients in this cohort stopped therapy, Dr. Barnes said he believes this study may prompt a reexamination of the factors associated with a lack of durability or earlier discontinuation.

“Although our options for the treatment of Crohn’s disease and ulcerative colitis continue to increase, these are not infinite, and thus there is a need for strategies to improve the durability of biologic therapies in patients with IBD,” he said. “These may emerge in the form of more targeted or personalized approaches to biologic therapies in future years, but currently, a continued assessment of an individual’s risk for early discontinuation may be the best approach, including risk factors such as number of prior biologics and potential need for combination therapy.”

David T. Rubin, MD, the Joseph B. Kirsner Professor of Medicine and chief of the Section of Gastroenterology, Hepatology and Nutrition at the University of Chicago, agreed it is crucial to better understand the reasons patients discontinue biologic therapy so that gastroenterologists can continue to improve the durability of these treatments.

“Understanding the multiple factors associated with primary nonresponse as well as loss of response is critical to our care of patients with IBD,” Dr. Rubin said. “This real-world study provides insights that can translate to our conversations with patients regarding the durability of therapies and inform additional work that we as physician-scientists must do to optimize therapies.”

—Adam Leitenberger

Dr. Barnes served as a consultant to AbbVie, Gilead, Pfizer and Takeda. Dr. Rubin disclosed financial relationships with AbbVie, Arena, Biomica, Bristol Myers Squibb, Ferring, Genentech/Roche, Janssen, Lilly, Merck and Takeda. The findings were reported at the 2020 AIBD meeting (abstract P27).