Abstract
BACKGROUND: The optimal treatment of perianal fistulizing Crohn's disease [PFCD] is unknown. We performed a systematic review with meta-analysis to compare combined surgical intervention and anti-tumour necrosis factor [anti-TNF] therapy [combined therapy] vs either therapy alone. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched systematically up to end December 2023. Surgical intervention was defined as an exam under anaesthesia ± setons. We calculated weighted risk ratios [RRs] with 95% confidence intervals [CIs] for our co-primary outcomes: fistula response and healing, defined clinically as a reduction in fistula drainage or number of draining fistulas and fistula closure respectively. RESULTS: Thirteen studies were analysed: 515 patients treated with combined therapy, 330 patients with surgical intervention, and 406 patients with anti-TNF therapy with follow-up between 10 weeks and 3 years. Fistula response [RR 1.10; 95% CI 0.93-1.30, p = 0.28] and healing [RR 1.06; 95% CI 0.86-1.31, p = 0.58] was not significantly different when comparing combined therapy with anti-TNF therapy alone. In contrast, combined therapy was associated with significantly higher rates of fistula response [RR 1.25; 95% CI 1.10-1.41, p < 0.001] and healing [RR 1.17; 95% CI 1.00-1.36, p = 0.05] compared with surgical intervention alone. Our results remained stable when limiting to studies that assessed outcomes within 1 year and studies where <10% of patients underwent fistula closure procedures. CONCLUSION: Combined surgery and anti-TNF therapy was not associated with improved PFCD outcomes compared with anti-TNF therapy alone. Due to an inability to control for confounding and small study sizes, future, controlled trials are warranted to confirm these findings.