Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease: Individual Participant Data Meta-Analysis of 309 Patients from 12 Studies.

BACKGROUND: The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk. METHODS: A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual participant data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as a (co)indication for start of anti-TNF therapy, more than three doses, and remission of luminal and pCD at anti-TNF discontinuation. The primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to re-treatment and risk factors associated with relapse as assessed by Cox regression analysis. RESULTS: In total, 309 patients from 12 studies in ten countries were included. The median duration of anti-TNF treatment was 14 months [interquartile range 5.8-32.5]. Most patients were treated for pCD without active luminal disease [89%], received first-line anti-TNF therapy [87%], and continued immunomodulatory therapy following anti-TNF discontinuation [78%]. The overall cumulative incidence of relapse was 36% (95% confidence interval [CI] 25-48%) and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation, respectively. Risk factors for relapse included smoking (hazard ratio [HR] 1.5 [1.0, 2.1]) and history of proctitis (HR 1.7 [1.1, 2.5]). The overall re-treatment response rate was 82%. CONCLUSIONS: This individual participant data meta-analysis, on predominantly patients with pCD without active luminal disease and first-line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup.

Is Intestinal Diversion an Effective Treatment for Distal Crohn's Disease?

BACKGROUND: Fecal diversion with an ileostomy is selectively used in cases of medically refractory Crohn's proctocolitis or advanced perianal disease. The aim of this study was to evaluate clinical improvement after fecal diversion in Crohn's disease (CD) and factors associated with clinical improvement. METHODS: A retrospective chart review of adult CD patients undergoing ileostomy formation for distal disease between 2000 and 2019 at 2 CD referral centers was conducted. The primary outcome was the rate of clinical improvement with diversion that allowed for successful restoration of intestinal continuity. Secondary outcomes included the rate of clinical and endoscopic improvement after fecal diversion, ileostomy morbidity, need for subsequent total proctocolectomy and end ileostomy, and factors associated with a clinical response to fecal diversion. RESULTS: A total of 132 patients with a median age of 36 years (interquartile range, 25-49) were included. Mean duration of disease was 16.2 years (10.4) years. Indication for surgery was medically refractory proctocolitis with perianal disease (n = 59; 45%), perianal disease alone (n = 24; 18%), colitis (n = 37; 28%), proctitis (n = 4; 3%), proctocolitis alone (n = 4; 3%), and ileitis with perianal disease (n = 4; 3%). Medications used before surgery included corticosteroids (n = 59; 45%), immunomodulators (n = 55; 42%) and biologics (n = 82; 62%). The clinical and endoscopic response to diversion was 43.2% (n = 57) and 23.9% (n = 16). At a median follow-up of 35.3 months (interquartile range, 10.6-74.5), 25 patients (19%) had improved and had ileostomy reversal, but 86 (65%) did not improve, with 50 (38%) undergoing total proctocolectomy for persistent symptoms. There were no significant predictors of clinical improvement. CONCLUSIONS: The use of a "temporary" ileostomy is largely ineffective in achieving clinical response.

Structured versus narrative reporting of pelvic MRI in perianal fistulizing disease: impact on clarity, completeness, and surgical planning.

OBJECTIVE: To evaluate clarity, completeness, and impact on surgical planning of MRI reporting of perianal fistulizing disease using a structured disease-specific template versus narrative reporting for planning of disease treatment by colorectal surgeons. MATERIALS AND METHODS: In this HIPAA-compliant, IRB-approved study with waiver of informed consent, a structured reporting template for perianal fistulizing disease MRIs was developed based on collaboration between colorectal surgeons and abdominal radiologists. The study population included 45 consecutive patients who underwent pelvic MRI for perianal fistulizing disease prior to implementation of structured reporting, and 60 consecutive patients who underwent pelvic MRI for perianal fistulizing disease after implementation of structured reporting. Objective evaluation of the reports for the presence of 12 key features was performed, as also subjective evaluation regarding the clarity and completeness of reports, and impact on surgical planning. RESULTS: Significantly more key features were absent in narrative reports [mean: 6.3 ± 1.8 (range 3-11)] than in structured reports [mean: 0.3 ± 0.9 (range 1-5)] (p ≤ 0.001). The use of structured reporting also increased the percentage of completeness (72.5-88.3% for surgeon 1, and 61.2-81.3% for surgeon 2; p = 0.05 and 0.03, respectively), helpfulness in surgical planning (7.1 ± 1.5-7.6 ± 1.5 for surgeon 1, and 5.8 ± 1.4-7.1 ± 1.1 for surgeon 2; p = 0.05 and p < 0.001, respectively), and clarity (7.6 ± 1.3-8.3 ± 1.1 for surgeon 1, and 5.2 ± 1.4-7.1 ± 1.3 for surgeon 2; p = 0.006 and p < 0.001, respectively) of the reports. CONCLUSION: Structured MRI reports in patients with perianal fistulizing disease miss fewer key features than narrative reports. Moreover, structured reports were described as more complete and clear, and more helpful for treatment planning.

Interdisciplinary Management of Perianal Crohn's Disease.

Perianal disease is a common manifestation of Crohn disease (CD) that results in significant morbidity and decreased quality of life. Despite several medical and surgical options, complex perianal CD remains difficult to treat. Before the advent of biologic therapy, antibiotics were the mainstay of medical treatment. Infliximab remains the most well-studied medical therapy for perianal disease. Surgical interventions are limited by the risk of nonhealing wounds and potential incontinence. When treatment options fail, fecal diversion or proctectomy may be necessary. Stem cell therapies may offer improved results and seem to be safe, but are not yet widely used.

Trends in the Surgical Management of Crohn's Disease.

INTRODUCTION: Although medical management of Crohn's disease has changed in recent years, it is unclear whether surgical management has altered. We examined rate changes of surgical interventions, stoma constructions, and subset of ileostomy and colostomy constructions. MATERIALS AND METHODS: We reviewed the Nationwide Inpatient Sample database from 1988 to 2011. We examined the number of Crohn's-related operations and stoma constructions, including ileostomies and colostomies; a multivariable logistic regression model was developed. RESULTS: A total of 355,239 Crohn's-related operations were analyzed. Operations increased from 13,955 in 1988 to 17,577 in 2011, p < 0.001. Stoma construction increased from 2493 to 4283, p < 0.001. The subset of ileostomies increased from 1201 to 3169, p < 0.001 while colostomies decreased from 1351 to 1201, p = 0.05. Operation percentages resulting in stoma construction increased from 18 to 24 %, p < 0.001. Weight loss (OR 2.25, 95 % CI 1.88, 2.69) and presence of perianal fistulizing disease (OR 2.91, 95 % CI 2.31, 3.67) were most predictive for requiring stoma construction. CONCLUSIONS: Crohn's-related surgical interventions and stoma constructions have increased. The largest predictors for stoma construction are weight loss and perianal fistulizing disease. As a result, nutrition should be optimized and the early involvement of a multidisciplinary team should be considered.