Steroid-Sparing Therapy Reduces Perianal Fistulizing Complications in Crohn's Disease

By Will Boggs MD

June 23, 2020

NEW YORK (Reuters Health) - The use of steroid-sparing therapy is associated with a significantly lower risk of perianal fistulizing complications (PFCs) in young patients with Crohn's disease (CD), according to a retrospective analysis.

"What I found most interesting about this study was not that using effective medicines to treat Crohn's disease was associated with lower risk of fistulas, but how big a difference they seem to make," Dr. Jeremy Adler of the University of Michigan, in Ann Arbor, told Reuters Health by email. "Our findings showed nearly 60% lower risk of developing fistulas in people treated with steroid-sparing therapies, compared to those not treated."

Fistulas develop in about 30% of individuals with childhood-onset CD and 15% to 20% of individuals with adult-onset CD, and PFCs can result in long-term health consequences and reduced quality of life. Steroid-sparing therapy (SST) improves many outcomes of CD, but whether it can prevent PFCs remains unclear.

Dr. Adler and colleagues used data from Optum's Clinformatics Data Mart to try to assess the effectiveness of SST for preventing PFCs among 2,214 children and young adults (aged 5 to 24 years at diagnosis) with newly diagnosed CD.

Overall, 56.1% of patients initiated SST, including immunomodulators alone (35.1%), anti-TNF-alpha alone (8.7%), or their combination (12.3%).

Within two years of the index date, 415 patients (18.7%) developed PFCs, the researchers report in JAMA Network Open.

The crude two-year rate of remaining free from PFCs was lower for patients who did not use SST (73.1%) than for patients who initiated SST (87.6%).

In the propensity-score-matched group of 972 pairs of patients, the crude two-year rate of remaining free from PFCs was significantly lower for patients who did not use SST (73.1%) than for patients who initiated SST (87.3%).

Among patients in the propensity-score-matched subgroup who developed PFCs, 55% fewer patients underwent ostomy after PFC if they had previously initiated SST, compared with those who did not initiate SST.

"This gives me hope that better treatment can improve outcomes, even if it can't always prevent fistulas." Dr. Adler said.

After adjusting for various characteristics, the use of SST was associated with a 59% lower risk of PFC development in the two years after CD diagnosis compared with no SST (P<0.001).

Antibiotic use was associated with a 23% lower risk of developing PFCs, whereas each additional year of age at CD diagnosis was associated with a 5% increased risk of developing PFCs.

In sensitivity analyses, the use of immunomodulators alone was associated with a 52% reduction in the risk of two-year PFC development. Anti-TNF-alpha alone was associated with a 47% reduction, and using both immunomodulators and anti-TNF-alpha was associated with an 83% lower risk, compared with no SST.

"Evidence like this study should encourage patients to use steroid-sparing therapies for treating Crohn's disease," Dr. Adler said. "Using nonimmune-suppressing therapies, or steroids, until someone develops disease complications is asking for trouble."

"Perianal fistula complications are common and can be severe," he concluded. "It's far better to prevent them than to try to treat them once they develop."

Dr. Sunanda V. Kane of Mayo Clinic, in Rochester, Minnesota, who wrote a linked editorial, told Reuters Health by email, "Steroid-sparing agents, while there might be daunting side effect profiles, really do change the natural history of Crohn's and prevent major complications."

"More research in this area is needed just to understand at a more individual-based level how we can change the natural history of Crohn's," she said.

Dr. Paulo G. Kotze of the Catholic University of Parana, in Curitiba, Brazil, who recently reviewed the modern management of perianal fistulas in CD, told Reuters Health by email, "It is important to control the disease with effective therapy (i.e., anti-TNFs in monotherapy or in combination therapy with immunomodulators) in the inflammatory phase, before development of penetrating complications, such as perianal fistulas. Effectiveness of therapy once fistulas are developed is not so significant."

To improve the uptake of SST in these patients, there is a need for "better diagnostic strategies, raising awareness among health practitioners, and easy access to the drugs, mostly with biosimilars that can reduce the cost of treatment," said Dr. Kotze, who was not involved in the study.

Dr. Jean-Frederic Colombel of Icahn School of Medicine at Mount Sinai, in New York City, who studies Crohn's disease, told Reuters Health by email, "Try to use steroids sparsely; avoid long-term exposure and repeated courses by using the drug-modifying agents that we have now, especially biologics and new small molecules."

"We are still struggling with treatment of these fistulas (the complex ones) when they develop," said Dr. Colombel, who also was not part of the study. "Once anti-TNF (especially infliximab) fails, there is no great medical resource. This is one of the biggest unmet needs in CD. This also deserves more studies about mechanisms of formation of perianal fistulas which is still a 'black box.'"

SOURCE: https://bit.ly/3fhfRoT and https://bit.ly/2Ythqt9 JAMA Network Open, online June 9, 2020.

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