Steroid-sparing therapy may reduce perianal fistula in Crohn’s disease

Steroid-sparing therapy (SST) more than halved the risk of perianal fistulizing complications (PFC)* among young patients with Crohn’s disease, according to a recent study.

“Compared with no SST, patients who initiated SST were 59 percent less likely to develop PFCs and fewer underwent ostomy,” noted the authors led by Dr Jeremy Adler from the University of Michigan, Ann Arbor, Michigan, US. “SST should be considered for treatment of Crohn’s disease to reduce the risk of PFCs.”

The authors of this retrospective study used the Optum’s Clinformatics Data Mart database to identify 2,214 patients who were aged 5–24 years at Crohn’s disease diagnosis and had no PFC (mean age at diagnosis 17 years, 52 percent male). Of these, 56.1 percent initiated SST before development of PFC or during the 24-month follow-up. Patients with a history of SST use, ulcerative colitis, or PFC prior to Crohn’s disease diagnosis were excluded. Propensity score matching compared use and non-use of SST (n=972 in each group). The patients were followed up for a median 1,351 days.

Within 2 years of Crohn’s disease diagnosis, 19.8 percent of patients developed PFCs, with SST use tied to a 59 percent significantly reduced risk of PFC compared with non-use (hazard ratio [HR], 0.41, 95 percent confidence interval [CI], 0.33–0.52; p<0.001). [JAMA Network Open 2020;3:e207378]

The researchers noted that PFC risk increased by 5 percent with each additional year of age at Crohn’s diagnosis (HR, 1.05; p<0.001). Presence of internal fistulas was also associated with an increased risk of PFCs (HR, 2.98; p=0.04), as was gastrointestinal bleeding (HR, 1.33; p=0.02). Conversely, antibiotic use was tied to a lower risk of developing PFCs (HR, 0.77; p=0.02).

Sensitivity analysis demonstrated that the lower risk of PFCs was consistent regardless of SST type, namely with immunomodulators only (HR, 0.48, 95 percent CI, 0.37–0.62; p<0.001) or anti-tumour necrosis factor α only (HR, 0.53, 95 percent CI, 0.36–0.78; p=0.001), with a greater effect noted with a combination of both (HR, 0.17, 95 percent CI, 0.09–0.30; p<0.001) over the 2 years compared with non-use of SST. The lower risk also persisted with regard to PFC development at 3 years (HR, 0.44) and 4 years (HR, 0.48; p<0.001 for both) post-Crohn’s diagnosis.

Of the patients who developed PFCs, 40 underwent ostomy** – a marker of PFC severity in this study – which was 55 percent less frequent with SSTs use vs non-use.

“Perianal fistulas have a devastating effect on quality of life (QoL) for people with Crohn’s disease,” said Adler. “Despite improvements in medical therapies, PFCs remain difficult to treat and commonly reoccur.” Surgery is often warranted, and despite that, the risk of requiring a permanent ostomy remains. As such, methods of PFC prevention are much needed, the authors said.

“Most of the research so far has focused on treating fistulas once they occur, but we found that effective therapy ahead of time may significantly reduce the risk of developing them in the first place,” said Adler.

“We need to advocate for broader use of drugs that are known to be effective in treating and controlling Crohn’s disease and that may help prevent lifelong complications for young patients,” he continued. “Our research supports efforts to provide the best-known therapy as early as possible to improve chances of altering disease course and preventing complications.”