Risk of PFCs lower with anti-TNF therapy if given early

Early treatment with tumour necrosis factor (TNF) inhibitors lowers the risk of perianal fistulizing complications (PFCs) in children and teens compared with no immunosuppression or immunomodulators without TNF inhibitors in a post-hoc analysis of a prospective observational study.

TNF inhibitors were linked to 83 percent lower odds (OR, 0.17, 95 percent confidence interval [CI], 0.05–0.57; p=0.0041) of developing PFCs compared with no immunomodulating treatment and 78 percent lower odds (OR, 0.22, 95 percent CI, 0.0540–0.90; p=0.035) compared with immunomodulators without anti-TNF therapy in propensity-matched patients. [CCC 2024, abstract 17]

The presence of perianal lesions more than tripled the odds of PFCs (OR, 3.86, 95 percent CI, 1.58–9.42; p=0.003).

The incidence of perianal fistula development in children is about 30 percent by 6 years after Crohn’s diagnosis, reported Dr Jeremy Adler from the University of Michigan in Ann Arbor, Michigan, US. They are more common in non-white and in Hispanic patients.

“Perianal fistulas are difficult to treat. They commonly reoccur, affect the quality of life, and increase costs of care three- to four-fold, depending on the study you’re looking at,’’ he emphasized.

Prevention better than cure

However, evidence from retrospective studies suggests that perianal fistulas may be preventable through early treatment. “It would be far better to prevent the complications than to treat them once they occur.”

Adler’s team analysed data from 447 patients <18 years of age, who were prospectively enrolled in the RISK cohort between 2008–2012.  They had perianal lesions, including skin tags or fissures.

The patients were divided into three groups – those receiving no immunosuppressive drugs, those taking immunomodulators (thiopurines or methotrexate), but no anti-TNF therapy, and those taking TNF inhibitors with or without immunomodulators or other medications. They were then tracked from enrolment until 3 months before PFC development or before the end of the study.

Patients were matched by gender, age at diagnosis, growth delay, deep endoscopic ulcers, small bowel involvement, and inflammatory burden (high, medium, or low), based on the weighted paediatrics Crohn’s disease activity index, platelets, albumin, erythrocyte sedimentation rate, and C-reactive protein.

The initial population included 873 patients. After propensity-score matching, each group had 149 patients.

Risk of PFCs reduced

Compared with predicted probability of PFC development over 3 years, early anti-TNF treatment reduced the risk of PFCs by 64 percent (p=0.0041) vs no immunomodulating therapy before propensity matching. Compared with immunomodulators alone, the risk of PFCs with anti-TNF therapy was 43 percent lower (p=0.035). Immunomodulators alone did not significantly reduce the risk of PFCs at all (p=0.59). In the matched cohort, there was a greater reduction in the risk of PFCs during anti-TNF therapy.

“Looking at the predictors of which patients developed the perianal fistulas, the one significant predictor was: did they or did they not have perianal lesions?” Adler said. “They have almost four-fold increased risk of developing perianal fistulas, and the only treatment with significance was the use of early anti-TNF medication.”

Patients with perianal lesions who received anti-TNF therapy had 96 percent lower odds (OR, 0.04, 95 percent CI, 0.0053–0.36; p=0.035) of developing PFCs vs no therapy while immunomodulators alone showed no reduced risk (p=0.10).

Commenting on the study, Dr Rebecca Gordon from Boston Children’s Hospital, Boston, Massachusetts, US said the findings had clinical implications even for paediatric clinicians who are not gastroenterologists.

“Knowing that there’s a potential intervention we can do to decrease the risk is helpful clinically,” she said. “The message for paediatricians is early treatment can make a difference.”