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Not All IBD Medications Linked to Increased Kidney Disease Risk

Azathioprine is linked to a slightly higher eGFR for patients with inflammatory bowel disease.

Ravy K. Vajravelu, MD

While the association between inflammatory bowel disease (IBD) and chronic kidney disease (CKD) is well known, how IBD medications increases the risk of CKD is not known.

A team of investigators from the Perelman School of Medicine at University of Pennsylvania, led by Ravy K. Vajravelu, MD, Division of Gastroenterology and Department of Medicine, determined whether IBD medications are linked to changes in estimated glomerular filtration rate (eGFR), a key indicator of kidney function.

The investigators performed a retrospective cohort study of the data from The Health Improvement Network. A total of 17,807 patients with inflammatory bowel disease were included and matched for age, sex, and practice with 63,466 individuals without IBD.

The team used a Cox proportional hazards model adjusted for common chronic kidney disease risk factors calculate the relative hazard of chronic kidney disease for stages 3 through 5D in patients with inflammatory bowel disease.

They also evaluated the association of 5-aminosalicylates (5-ASAs), azathioprine, and methotrexate with change in eGFR using a longitudinal model.

After controlling for the risk factors associated with chronic kidney disease, the investigators discovered inflammatory bowel disease is associated with the development of chronic kidney disease in patients between 16-77 years old.

However, as patients age increased, the adjusted hazard ratio for chronic kidney disease decreased monotonically significantly.

The adjusted hazard ratio decreased from 7.88 (95% CI, 2.56—24.19) at age 16 to 1.13 (95% CI, 1.01–1.25) at age 77.

Using the longitudinal analysis, the investigators discovered that exposure to 5-ASAs or methotrexate was not linked to changes in eGFR. On the other hand, azathioprine was associated with a slightly higher eGFR (.32 mL/min/1.73m2; 95% CI, 0.16-0.48).

“In a retrospective study of more than 80,000 persons, we found that IBD is associated with increased risk of CKD, and the hazard ratio is highest among younger patients,” the authors wrote. “Commonly used non-biologic therapeutic agents were not associated with lower eGFR.”

There have been a number of new treatment options developed in recent years to treat inflammatory bowel disease.

A number of studies presented at the American College of Gastroenterology’s Annual Scientific Meeting (ACG 2019) focused on ustekinumab, including the UNIFI study that showed the medication is safe and effective in treating ulcerative colitis.

In an interview with HCPLive®, Maria Abreu, MD, director of the Crohn’s & Colitis Center at the University of Miami Health Center, said the UNIFI study shows the promising future of ustekinumab.

During ACG 2019, investigators also presented data on a new type of vedolizumab (VDZ) therapy could help patients suffering from moderate-to-severe ulcerative colitis.

Vedolizumab is a monoclonal antibody targeting α4β7 integrin that is currently approved as an intravenous formulation to treat ulcerative colitis.

The new data comes from the first ever completed study with a new vedolizumab subcutaneous (SC) formulation, a randomized, double-blind, double-dummy, placebo-controlled, phase 3 trial assessing vedolizumab subcutaneous as a maintenance treatments in adults with moderately to severely active ulcerative colitis.

Patients who transition to vedolizumab subcutaneous after 2 infusions of vedolizumab had a clinical remission rate of 46.2% and a clinical response rate of 65.1% after 52 weeks.

However, patients who received 3 vedolizumab intravenous infusions before transitioning to the subcutaneous version had a 39.2% clinical remission rate, while 48.0% achieved a clinical response after 54 weeks.

With a number of treatments now available, it is not currently known what factors affect the risk of chronic kidney disease in patients with inflammatory bowel disease.

There has been inconsistent evidence linking the use of 5-ASAs with an increased risk of chronic kidney disease.

The study, “Inflammatory Bowel Diseases Are Associated With an Increased Risk for Chronic Kidney Disease, Which Decreases With Age,” was published online in Clinical Gastroenterology and Hepatology.