Studies Investigate Drug Survival, Discontinuation of Biologics in IBD

In patients with ulcerative colitis and Crohn disease, treatment with biologics is often effective, but adverse events or loss of response may lead to discontinuation. Several studies that will be presented at this week’s European Crohn’s and Colitis Organisation’s 14th Congress, held in Copenhagen, Denmark, sought to investigate factors related drug survival and discontinuation of biologic therapies for inflammatory bowel disease (IBD).
Kelly Davio
March 05, 2019
In patients with ulcerative colitis (UC) and Crohn disease (CD), treatment with biologics is often effective, but adverse events (AEs) or loss of response may lead to discontinuation. Several studies that will be presented at this week’s European Crohn’s and Colitis Organisation’s 14th Congress, held in Copenhagen, Denmark, sought to investigate factors related drug survival and discontinuation of biologic therapies for inflammatory bowel disease (IBD).

A retrospective study conducted among patients included in a database at a single gastroenterology center in Ireland sought to understand which factors can determine the sustainability of biologic treatment for patients with IBD.1

A total of 765 patients had complete data available and were included in the analysis. In total, 539 were biologic naïve when they began treatment with infliximab, adalimumab, vedolizumab, or golimumab. In total, 35.6% of patients had UC, while 64.4% had CD. The median time to discontinuation among biologic-naïve patients was 2.84 years in the UC group, while it was 3.59 years in the CD group.

There were 226 patients who had previous experience with biologics when they were treated with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab. Of this group, 32.74% had UC and 65.93% had CD. Median time to discontinuation was 2.58 years in the UC group and 3.83 years in the CD group.

While there was no significant difference in time to discontinuation in the biologic-experienced versus biologic-naïve patients, patients with UC were less able to sustain treatment with their biologic therapies.

Another study examined drug survival among different anti–tumor necrosis factor (anti-TNF) agents, particularly with respect to second-line anti-TNF therapy.2 The study drew from the Swedish National Quality Registry for IBD (SWIBREG). In total, 955 patients with IBD who started their first anti-TNF drug between 2006 and 2016 were identified in the SWIBREG database.

The investigators found that risk factors for shorter drug survival in patients with CD included use of infliximab as a first-line agent (versus adalimumab) and colonic disease (versus ileal disease). Patients with CD who switched from adalimumab to infliximab had shorter drug survival compared to those who switched from infliximab to adalimumab.

Normalization of C-reactive protein levels at 3 months was associated with decreased risk of short drug survival in patients with both CD (adjusted hazard ratio [HR], 0.40; 95% CI, 0.19-0.81) and UC (adjusted HR, 0.40; 95% CI, 0.19-0.86). In CD, but not UC, use of immunomodulators was associated with a lower risk of short drug survival due to AEs (adjusted HR, 0.50; 95% CI, 0.31‒0.82).

However, discontinuation not undesirable in all cases; given the AEs associated with long-term treatment with infliximab, as well as biologic therapy’s high cost burden, it may be feasible to stop infliximab in patients with inflammatory bowel disease (IBD) who have achieved sustained remission.

A single-center retrospective analysis, conducted at an Irish hospital, found low relapse rates among patients with CD and UC who discontinued treatment after achieving sustained remission.3

In the study, 30 patients who discontinued infliximab due to sustained remission (as defined by clinical, endoscopic, and biomarker criteria) were assessed at baseline, and at 3, 6, 12, and 24 months after discontinuation. Patients’ mean length of infliximab treatment before discontinuation was 38.5 months.

At 24 months after discontinuation, 91% of the 22 patients with available data remained in clinical remission. After stopping infliximab, 50% of patients took no other medications for their IBD. In total, 13.3% of patients had relapsed, and restarted biologic therapy. A cost analysis showed that discontinuing infliximab saved the hospital the equivalent of $429,493 over the study period.

According to the investigators, discontinuing infliximab in patients with sustained remission was safe and offered significant savings to the healthcare system.

References
1. Doherty J, Buckley M, Cullen G, et al. Sustainability of biologic therapies is less in UC than CD patients independent of prior biologic experience. Presented at the 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P405. ecco-ibd.eu/publications/congress-abstract-s/item/p405-sustainability-of-biologic-therapies-is-less-in-uc-than-cd-patients-independent-of-prior-biologic-experience.html.

2. Visuri I, Eriksson C, Mårdberg E, et al. Anti-TNF agent drug survival in patients with IBD: real-world comparisons of individual anti-TNF agents based on the Swedish National Quality Registry for IBD (SWIBREG). Presented at the 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P649. ecco-ibd.eu/publications/congress-abstract-s/item/p649-anti-tnf-agent-drug-survival-in-patients-with-ibd-real-world-comparisons-of-individual-anti-tnf-agents-based-on-the-swedish-national-quality-registry-for-ibd-swibreg.html.

3. Ryan T, Coffey L, Mullen A, Leyden J, MacMathuna P. Sustained remission in inflammatory bowel disease patients after discontinuing infliximab; the ongoing reluctance to stop biologics. Presented at the 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P557. ecco-ibd.eu/publications/congress-abstract-s/item/p557-sustained-remission-in-inflammatory-bowel-disease-patients-after-discontinuing-infliximab-the-ongoing-reluctance-to-stop-biologics.html.

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