Medical Professional Publications

Thiopurines Disappoint in Real-World Crohn’s Care

(From the March 2015 Issue of PediatricsOnline)

An initial randomized-controlled trial evaluating thiopurines, a drug for Crohn’s disease management, found the drug to be exceptionally successful — keeping greater than 90 percent of its pediatric users in clinical remission through 18 months. But real-world clinical experiences suggest that success rate may be considerably reduced, according to studies such as the one published in the World Journal of Gastroenterology by clinician-researchers at Nationwide Children’s Hospital.

“It’s not uncommon for the results of initial trials to differ somewhat from real-world studies,” explains Brendan M. Boyle, MD, MPH, a gastroenterologist at Nationwide Children’s and lead author of the study. “But we found a substantial difference, as have other adult and pediatric studies that have emerged.”

Dr. Boyle and his colleagues in the Division of Gastroenterology, Hepatology and Nutrition retrospectively analyzed data from the multi-center Pediatric Inflammatory Bowel Disease Network (PIBDNet) cohort study. Thiopurine-naïve children treated with mercaptopurine (6MP) or azathioprine who achieved remission were evaluated for time to disease relapse.

Of the 65 patients who achieved remission within 180 days of initiating thiopurines only 47 and 23 percent of these patients remained in remission six and 12 months later, respectively.

Data from this study does not clearly indicate why patients experienced a dramatic decrease in remission maintenance compared to the initial trial, but Dr. Boyle believes it is likely a combination of factors, which could include variable dosing, differences in drug level monitoring and uncertainty about adherence to therapy.

“Practitioners agree that thiopurines still have a place in the treatment of pediatric Crohn’s disease and can successfully maintain remission for many patients,” Dr. Boyle says. “Fortunately, patients who do not respond to thiopurines can often successfully be switched to another class of drugs, with the availability of anti-TNF therapy.”

Improvements in the measurement of disease indicators, as well as the emergence of new therapeutics, may also render the findings on thiopurines less disappointing than would have otherwise been the case.

“Thiopurines have long been a mainstay of the treatment of Crohn’s disease in children, in large part due to a single prospective study showing impressive results,” says Wallace V. Crandall, MD, senior author on the study, director of the Inflammatory Bowel Disease Center and medical director of Quality Improvement at Nationwide Children’s. “We sought to understand the real-world outcomes of thiopurine treatment to better appreciate its position in the treatment of pediatric Crohn’s disease.”

Although Dr. Boyle and Dr. Crandall acknowledge their study’s small sample size and inconsistent indicators of disease remission across practices, they point out that other studies of real-world cohorts have found similar rates of thiopurine effectiveness.

More recently, the IBD Center at Nationwide Children’s has also participated in the multi-center, prospective RISK cohort study that included patients with newly diagnosed Crohn’s disease. Dr. Boyle and Dr. Crandall anticipate that the results of the RISK study will further inform clinicians’ decisions about initial medication selection and help inform families and practitioners about expected responses to therapy.

Boyle BM, Kappelman MD, Colletti RB, Baldassano RN, Milov DE, Crandall WV. Routine use of thiopurines in maintaining remission in pediatric Crohn's disease. World Journal of Gastroenterology. 2014 Jul 21, 20(27):9185-90.

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