Discontinuation of anti–tumor necrosis factor (TNF) therapy in patients with perianal Crohn disease (PCD) may increase the risk for fistula relapse, according to study results published in Inflammatory Bowel Diseases.

Fistula relapse occurs in 20% to 30% of patients with PCD within the first year despite management with surgery and medications. Results from previous studies have identified young age, disease location, and history of abdominal surgery as predictors of fistula relapse; however, more data are needed to determine the type of anti-TNF that may contribute to a high fistula relapse risk. The objective of this study was to identify additional predictive factors of fistula relapse in patients in remission after PCD treatment.

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In this retrospective single-center study, researchers examined 137 patients corresponding to 157 abscess events who were treated for fistulizing PCD and who had achieved clinical remission within 3 months after surgery. Remission was defined as the absence of anal pain and draining fistula during a clinical examination. The primary outcome was the occurrence of a fistula relapse at follow-up, which was defined as a subsequent perianal draining fistula or abscess confirmed by clinical examination and/or by pelvic magnetic resonance imaging. A Cox regression model was used to identify predictors of fistula relapse.

Results revealed that when comparing patients who received anti-TNF therapy after fistula surgery (n=120 abscess events) with those who did not (n=37 abscess events), patients who received anti-TNF therapy tended to be younger (34 vs 40 years; P <.01) and had a more complex fistula (58% vs 29%; P <.01) with more seton placement (68% vs 35%; P <.01) or conservative surgery (41% vs 16%; P =.01). No death occurred during follow-up (median duration 43 months, interquartile range 26-64 months), although 34 patients experienced fistula relapse. Survival rates without fistula relapse were 97% at 1 year, 78% at 3 years, and 74% at 5 years.

The rate of fistula relapse-free survival was not different between patients treated with infliximab or adalimumab (P =.66). In multivariate analysis, an increased risk of fistula relapse was independently associated with discontinuation of anti-TNF therapy (odds ratio [OR] 3.49; 95% CI, 1.05-11.65; P =.04), colonic location (OR 6.25; 95% CI, 1.54-25.40; P =.01), and stricturing phenotype (OR 4.39; 95% CI, 1.51-12.77; P =.01). Discontinuation of immunosuppression therapy was associated with a reduced risk of fistula relapse (OR 0.24; 95% CI, 0.06-0.94; P =.04).

This study has several limitations. First, the definition of PCD remission after the initial surgery and fistula relapse at follow-up were not documented by magnetic resonance imaging in all patients, and there was no clear radiological criteria to define fistula healing. Second, the low recurrence rate observed in this cohort may be attributed to the low number of patients with active luminal Crohn disease and to the fact researchers selected only patients who experienced remission at 3 months. Last, there was no definitive surgical procedure for PCD, which may explain the high relapse rate after discontinuation of treatment. 

The study researchers concluded that in patients who achieve fistula remission of PCD, relapse rates are not different between infliximab and adalimumab, and that discontinuing these therapies may be associated with an increased risk of fistula relapse. They recommend that “de-escalation strategy should be cautious in patients with a history of PCD.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Malian A, Rivière P, Bouchard D, et al. Predictors of perianal fistula relapse in Crohn’s disease [published online August 30, 2019]. Inflamm Bowel Dis. doi: 10.1093/ibd/izz198