Combo therapy in IBD: Is de-escalation possible after 1 year?

Clinicians should consider de-escalating combination therapy with immunomodulators to a monotherapy after 1 year in patients with inflammatory bowel disease (IBD), says an expert at Crohn’s and Colitis Congress 2023.

“Combination therapy is one of the most, if not the most, effective therapies for IBD … for example, the combination of thiopurine and anti-tumour necrosis factor (anti-TNF) agents,” said Dr Ryan Ungaro, associate professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, New York, US. “Let us not forget as well that in the seminal SONIC trial, infliximab and thiopurines were superior to both monotherapies.” 

“So why would we consider de-escalating combination therapy if it’s so effective in IBD?” he asked. “Practical reasons for de-escalation include safety, patient concern, and adherence or ease,” he offered. [CCC 2023, abstract Sp103]

The evidence at hand

Ungaro reviewed results of a nationwide cohort study showing that combination therapy correlated with an elevated risk of both serious infection (hazard ratio [HR], 1.23, 95 percent confidence interval [CI], 1.05–1.45) and opportunistic infection [HR, 1.96, 95 percent CI, 1.32–2.91) when compared with anti-TNF therapy in patients with IBD. [Gastroenterology 2018;doi:10.1053/j.gastro.2018.04.012]

Moreover, exposure to combination therapy was associated with a small but statistically significant increased risk for lymphoma (aHR, 6.11, 95 percent CI, 3.46–10.8; p<0.001) in patients with IBD compared with use of thiopurine monotherapy (aHR, 2.35, 95 percent CI, 1.31–4.22; p<0.001) or anti-TNF monotherapy alone (aHR, 2.53, 95 percent CI, 1.35–4.77; p<0.001 [JAMA 2017;doi:10.1001/jama.2017.16071]

Immunomodulator withdrawal: Good or bad?

A retrospective analysis meanwhile showed that immunomodulator withdrawal from anti-TNF therapy in patients with Crohn’s disease was not associated with loss of response within 1–2 years. [Clin Gastroenterol Hepatol 2022;doi:10.1016/j.cgh.2022.01.019]

“If confirmed by future randomized controlled prospective studies, immunomodulator withdrawal from anti-TNF therapy may be considered a de-escalation strategy in patients with IBD,” said the study authors.

Meanwhile, in the DIAMOND2 trial, continuation of thiopurines for over 6 months offered no clear benefit over scheduled anti-TNF monotherapy among patients with Crohn’s disease (CD) in remission with combination therapy. At week 52, rates of endoscopic remission were comparable between groups. [J Gastroenterol 2019;54:860-870]

Interestingly, withdrawal of an anti-TNF therapy (infliximab) was associated with a higher risk of relapse and reduced time in remission among patients with CD. Treatment resumption resulted in rapid remission. [J Crohns Colitis 2022;doi.org/10.1093/ecco-jcc/jjab232.000]

Why de-escalate combo therapy?

“Clearly, evidence supports de-escalating combo therapy to stopping immunomodulators,” Ungaro pointed out. “First, it decreases the risk of infection and cancer and makes our lives and that of our patients’ easier. Second, there is good prospective data that there are similar outcomes with stopping immunomodulators to continuing combination therapy.”