Tumor Necrosis Factor (TNF) Antagonists in Treatment of Internal Fistulizing Crohn’s Disease

Bouguen G, et al.; GETAID. Efficacy and Safety of Tumor Necrosis Factor Antagonists in Treatment of Internal Fistulizing Crohn’s Disease. Clin Gastroenterol Hepatol. 2020 Mar; 18(3):628-636.

Results: After a median follow-up period of 3.5 years, 68 patients (43.6%) underwent a major abdominal surgery. The cumulative probabilities for being surgery-free were 83%, 64%, and 51% at 1, 3, and 5 years, respectively. A concentration of C-reactive protein >18 mg/L, an albumin concentration <36 g/L, the presence of an abscess at the fistula diagnosis, and the presence of a stricture were associated independently with the need for surgery. The cumulative probabilities of fistula healing, based on imaging analyses, were 15.4%, 32.3%, and 43.9% at 1, 3, and 5 years, respectively. Thirty-two patients (20.5%) developed an intestinal abscess and 4 patients died from malignancies (3 intestinal adenocarcinomas). One patient died from septic shock 3 months after initiation of anti-TNF therapy.

Conclusions: In a retrospective analysis of data from a large clinical trial, we found that anti-TNF therapy delays or prevents surgery for almost half of patients with CD and luminal fistulas. However, anti-TNF therapy might increase the risk for sepsis-related death or gastrointestinal malignancies.

Kobayashi T, et al. Real-world Experience of Anti-tumor Necrosis Factor Therapy for Internal Fistulas in Crohn’s Disease: A Retrospective Multicenter Cohort Study. Inflamm Bowel Dis. 2017 Dec;23(12):2245-2251.

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Results: A total of 93 Crohn’s disease cases were included in the study with a mean follow-up period of 1452.8 days. Fistula locations were entero-entero/colonic (n = 72, 77.4%), enterovesical (n = 16, 17.2%), or enterovaginal (n = 5, 5.4%). Cumulative surgery rate was 47.2%, and fistula closure rate was 27.0% at 5 years from the induction of anti-TNF agents. Lower Crohn’s Disease Activity Index and shorter duration from the diagnosis of fistula were independently associated with the lower risk of surgery (P = 0.017 and 0.048, respectively). Single fistula was associated with the successful fistula closure. Second-line surgical treatments were mostly successful for anti-TNF failures.

Conclusions: In the present retrospective cohort study, approximately half of patients with internal fistulas avoided surgery for long periods. It may be reasonable to treat quiescent single internal fistulas with anti-TNF agents soon after the diagnosis of internal fistulas.

Tandon P, et al. Strategies to Optimize Anti-tumor Necrosis Factor Therapy for Perianal Fistulizing Crohn’s Disease: A Systematic Review. Dig Dis Sci. 2019 Nov; 64(11):3066-3077.

“Twelve studies compared anti-TNF therapy alone versus a combined approach: four with surgery, three with antibiotics, and five with immunomodulators. Only two studies, both with antibiotics, were rated high quality. The addition of antibiotics to anti-TNF therapy resulted in significantly higher rates of fistula response and healing in one study, and a trend toward reduction in fistula drainage in the other. Three of four studies found higher rates of fistula healing when surgery was combined with TNF antagonists. In contrast, one of five studies found a trend toward higher rates of fistula healing in patients treated concomitantly with immunomodulators. Five observational studies assessed the association between anti-TNF concentration and fistula healing. Higher infliximab serum concentrations were consistently associated with fistula healing. In conclusion, few high-quality studies assessing strategies to optimize anti-TNF therapy for PCD exist. Although antibiotics, possibly surgery, and higher serum infliximab concentrations appear to improve fistula healing, future prospective studies are needed to determine the optimal treatment strategy.”

See also: Crohn’s Disease: Biologics and immunomodulators

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