Study shows SST reduces risk of perianal fistulizing complication in young patients

Steroid-sparing therapy (SST) reduces the risk of perianal fistulizing complications in young patients with Crohn’s disease.

Patients who initiated SST were 59% less likely to develop perianal fistulizing complications and were less likely to undergo ostomy than patients with no SST, according to a study published in JAMA Network Open.

Jeremy Adler, MD, MSc, Department of Pediatrics, University of Michigan, and colleagues wrote that the results of the study indicate that perianal fistula complications may be preventable, and that SST should be considered for all patients with Crohn’s disease.

Patients with Crohn’s disease (CD) can develop severe destructive transmural intestinal inflammation that results in fistulas that penetrate through the bowel wall. Perianal fistula complications (PFCs) develop in 15%-30% of patients with CD, most commonly among those with childhood-onset CD. These complications are difficult and costly to treat and have a debilitating effect on a patient’s quality of life.

They are also likely to recur.

In fact, about 70% of patients with PFCs eventually have some kind of surgical intervention, and between 8% and 19% resort to permanent diverting ostomy. Therefore, it is important to develop effective medical treatments to avoid the development of PFCs.

SST, which includes immunomodulators and anti-tumor necrosis factor α (anti-TNFα) medications, has been shown to improve CD outcomes. In this study Adler and colleagues wanted to see whether SST use is associated with preventing the development of PFCs in young patients diagnosed with CD.

The authors, using commercial administrative claims from Jan. 1, 2001 through June 30, 2016, conducted a comparative effectiveness analysis of 2,214 patients (median age at CD diagnosis of 17.0 year) between the ages of 5 and 24. Patients with PFCs or SST use at or before CD diagnosis were excluded from the study. SST was defined as the use of immunomodulators thiopurines and methotrexate, and/or the anti-TNFα medications infliximab, adalimumab, and certolizumab pegol.

Of the patients in the study, 56.1% initiated SST before PFC development or by the end of the 2-year study period, while the remaining 43.9% did not.

After propensity matching, 384 of 1944 patients in the entire study group (19.8%) developed PFCs within 2 years of the index date. The 2-year rate of remaining free from PFCs was 73.1% for patients who did not use SST versus 87.3% for patients who initiated SST, and the use of SST was associated with a 59% decreased risk of PFC development compared with no SST.

In addition, Adler and colleagues found that:

  • Among those who developed PFCs, 55% fewer SST users underwent ostomy than SST nonusers.
  • The use of immunomodulators alone, was associated with a 52% reduction in the risk of 2-year PFC development (HR, 0.48; 95% CI, 0.37-0.62).
  • The use of anti-TNFα alone was associated with a 47% risk reduction (HR, 0.53; 95% CI, 0.36-0.78).
  • Combined immunomodulator and anti-TNFα therapy was associated with an 83% risk reduction (HR, 0.17; 95% CI, 0.09-0.30).

Adler and colleagues noted that the use of SST in the study population was less common than guidelines recommend and requires further investigation.

’The study findings support existing guidelines, which recommend SST use for all patients with CD,” the authors concluded. “Most important, we believe that these results provide an evidence base on which to develop strategies for prevention of PFCs in young patients with CD.”

In a commentary accompanying the study, Sunanda V. Kane, MD, MSPH, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, observed that this study’s findings “should be compelling to parents and patients.”

“The benefits of avoiding surgery, pain, and physiologic dysfunction cannot be understated,” wrote Kane. “So why then do more clinicians not prescribe SST therapy in patients with Crohn disease?”

A lack of knowledge about the efficacy of SST can be eliminated with education, wrote Kane. She also suggested there could also be an exaggerated fear of adverse effects among patients, particularly considering that research indicates patients are more willing to accept risk if a treatment will provide appropriate efficacy and an improved quality of life, and that the risk of complications associated with active inflammation is higher than risks of adverse effects from medications.

“Ultimately, individualizing care based on risk factors of disease and on patient preference, along with shared decision-making, will help change the future natural history of Crohn disease,” she wrote.

  1. The use of steroid-sparing therapy reduces the risk of the development of perianal fistulizing Crohn’s disease.

  2. The study found that patients who initiated SST were 59% less likely to develop perianal fistulizing complications.

Michael Bassett, Contributing Writer, BreakingMED™

Adler reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH), the Shaevsky Family Research Fund for Crohn’s Disease, the Crohn’s & Colitis Foundation, and the Patient-Centered Outcomes Research Institute.

Cat ID: 188

Topic ID: 77,188,730,188,20,192,925