Short-term anti-tumor necrosis factor (anti-TNF) therapy combined with surgical closure is superior to anti-TNF treatment alone for inducing radiological healing in patients with Crohn disease and active high perianal fistulas, according to a study published in The Lancet Gastroenterology & Hepatology.
In this multicenter, patient preference, randomized study (PISA-II), researchers enrolled patients with Crohn disease aged 18 years and older who had an active, high perianal fistula with a single internal opening (N=94). Patients were treated according to their preference. Those without a distinct preference for either treatment approach were evenly and randomly assigned to 1 of the 2 groups; patients with a specific preference received that treatment.
The treatment protocols were the same in both cohorts. In the anti-TNF treatment group (n=56), a loading dose of 5 mg/kg infliximab was administered at 2 and 6 weeks, and thereafter every 8 weeks for 1 year. In the surgical closure group (n=38), patients underwent either the advancement flap or ligation of the intersphincteric fistula tract procedure. Anti-TNF therapy was discontinued around 4 months at the discretion of the treating physician.
An MRI was conducted at the 18-month follow-up in 84% of the surgical closure group (n=32) and 91% of the anti-TNF group (n=51). The primary outcome, radiological healing assessed by MRI, was reported in 32% of the surgical closure group (n=12) and in 9% of patients in the anti-TNF group (n=5; P =.005), the significance of which was confirmed by post-hoc as-treated analysis.
When assessing clinical closure in the intention-to-treat analysis, there was no significant difference between the surgical closure group (68%, n=26) and the anti-TNF group (52%, n=29; P =.076), but there was a significant difference between groups in a post-hoc as-treated analysis, with higher clinical closure rates in the surgical closure group (71%, n=32) than in the anti-TNF group (50%, n=22; P =.016).
Study limitations included not achieving full randomization due to the patient preference design. Some clinically relevant differences between the groups could not be excluded despite baseline characteristics that were not significantly different. Researchers did not collect data on incontinence, which is an important consideration in counseling patients toward an objective and clear potential disadvantage in pursuing surgical closure. Researchers are currently analyzing incontinence data to report at a later date.
“…[T]his study shows that short-term anti-TNF therapy combined with surgical closure induces radiological healing, assessed by MRI, more frequently than anti-TNF therapy,” the study authors wrote. “On the basis of these data, we believe that patients with [Crohn disease] perianal fistula amenable for surgical closure should be counselled for this therapeutic approach.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Meima-van Praag EM, van Rijn KL, Wasmann KATGM, et al. Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy in the treatment of perianal fistulas in Crohn’s disease (PISA-II): a patient preference randomized trial. Lancet Gastroenterol Hepatol. Published April 12, 2022. doi:10.1016/S2468-1253(22)00088-7