1.Factors associated with anti-tumor necrosis factor effectiveness to prevent postoperative recurrence in Crohn’s disease
Anthony BUISSON ; Lisa CANNON ; Konstantin UMANSKIY ; Roger D. HURST ; Neil H. HYMAN ; Atsushi SAKURABA ; Joel PEKOW ; Sushila DALAL ; Russell D. COHEN ; Bruno PEREIRA ; David T. RUBIN
Intestinal Research 2022;20(3):303-312
Background/Aims:
We assessed the effectiveness of anti-TNF agents and its associated factors to prevent endoscopic and clinical postoperative recurrence (POR) in Crohn’s disease (CD).
Methods:
From a prospectively-maintained database, we retrieved 316 CD patients who underwent intestinal resection (2011–2017). Endoscopic (Rutgeerts index ≥ i2 at 6 months) and clinical (recurrence of symptoms leading to hospitalization or therapeutic escalation) POR were assessed.
Results:
In 117 anti-TNF-naïve patients, anti-TNF therapy was more effective than immunosuppressive agents (odds ratio [OR], 8.8; 95% confidence interval [CI], 1.8–43.9; P= 0.008) and no medication/5-aminosalicylates (OR, 5.2; 95% CI, 1.0–27.9; P= 0.05) to prevent endoscopic POR. In 199 patients exposed to anti-TNF prior to the surgery, combination with anti-TNF and immunosuppressive agents was more effective than anti-TNF monotherapy (OR, 2.32; 95% CI, 1.02–5.31; P= 0.046) to prevent endoscopic POR. Primary failure to anti-TNF agent prior to surgery was predictive of anti-TNF failure to prevent endoscopic POR (OR, 2.41; 95% CI, 1.10–5.32; P= 0.03). When endoscopic POR despite anti-TNF prophylactic medication (n = 55), optimizing anti-TNF and adding an immunosuppressive drug was the most effective option to prevent clinical POR (hazard ratio, 7.38; 95% CI, 1.54–35.30; P= 0.012). Anti-TNF therapy was the best option to prevent clinical POR (hazard ratio, 3.10; 95% CI, 1.09–8.83; P= 0.034) in patients with endoscopic POR who did not receive any biologic to prevent endoscopic POR (n = 55).
Conclusions
Anti-TNF was the most effective medication to prevent endoscopic and clinical POR. Combination with anti-TNF and immunosuppressive agents should be considered in patients previously exposed to anti-TNF.
2.Vedolizumab for perianal fistulizing Crohn’s disease: systematic review and meta-analysis
Fares AYOUB ; Matthew ODENWALD ; Dejan MICIC ; Sushila R. DALAL ; Joel PEKOW ; Russell D. COHEN ; David T. RUBIN ; Atsushi SAKURABA
Intestinal Research 2022;20(2):240-250
Background/Aims:
Perianal fistulas are a debilitating manifestation of Crohn’s disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management of fistulizing CD continues to be challenged by unmet needs. We conducted a systematic review and meta-analysis of the effectiveness of vedolizumab for the management of perianal fistulizing CD.
Methods:
A search of PubMed, EMBASE and the Cochrane Library was performed from inception to June 2020 for studies reporting rates of perianal fistula healing in CD patients treated with vedolizumab. The primary outcome of interest was complete healing of perianal fistulas and the secondary outcome was partial healing. The pooled fistula healing rates with 95% confidence intervals (CI) were calculated utilizing a random effects model.
Results:
A total of 74 studies were initially identified, 4 of which met the inclusion criteria. A total of 198 patients with active perianal fistulas were included, 87% of whom had failed previous anti-TNF therapy. The pooled complete healing rate was 27.6% (95% CI, 18.9%–37.3%) with moderate heterogeneity (I2=49.4%) and the pooled partial healing rate was 34.9% (95% CI, 23.2%–47.7%) with high heterogeneity (I2=67.1%).
Conclusions
In a meta-analysis of 4 studies that included 198 patients with perianal fistulizing CD, the majority of whom had failed previous anti-TNF therapy, vedolizumab treatment led to healing of perianal fistulas in nearly one-third of the patients. The lack of high-quality data and significant study heterogeneity underscores the need for future prospective studies of fistula healing in patients receiving anti-integrin therapy.