Top-down Versus Step-up Strategies to Prevent Postoperative Recurrence in Crohn's Disease.

BACKGROUND: The best management after ileocolonic resection is still unknown in Crohn's disease (CD). We compared step-up and top-down approaches to prevent short and long-term postoperative recurrences in CD patients. METHODS: From a comprehensive database, consecutive CD patients who underwent intestinal resection (2014-2021) were included. Top-down (biologics started within the first month after surgery) or step-up strategies (no biologic between surgery and colonoscopy at 6 months) were performed with systematic colonoscopy at 6 months and therapeutic escalation if Rutgeerts index was ≥i2a (endoscopic postoperative recurrence). Propensity score analysis was applied for each comparison. RESULTS: Among 115 CD patients, top-down was the most effective strategy to prevent endoscopic postoperative recurrence (46.8% vs 65.9%, P = .042) and to achieve complete endoscopic remission (Rutgeerts index = i0; 45.3% vs 19.3%; P = .004) at 6 months. We did not observe any significant difference between the 2 groups regarding clinical postoperative recurrence (hazard ratio [HR], .86 [0.44-1.66], P = .66) and progression of bowel damage (HR, 0.81 [0.63-1.06], P = .12). Endoscopic postoperative recurrence at 6 months was associated with increased risk of clinical postoperative recurrence (HR, 1.97 [1.07-3.64], P 0.029) and progression of bowel damage (HR, 3.33 [1.23-9.02], P = .018). Among the subgroup without endoscopic postoperative recurrence at 6 months, the risks of clinical postoperative recurrence and progression of bowel damage were significantly improved in the top-down group (HR, 0.59 [0.37-0.94], P = .025; and HR, 0.73 [0.63-0.83], P < .001, respectively). CONCLUSIONS: Top-down strategy should be the preferred management to prevent short and long-term postoperative recurrence in CD.

Our data suggest that top-down strategy should be preferred to step-up approach to prevent endoscopic postoperative recurrence, as well as clinical postoperative recurrence and progression of bowel damage in most of the patients with Crohn's disease after bowel resection.

Effectiveness of Switching From Intravenous to Subcutaneous Infliximab in Patients With Inflammatory Bowel Diseases: the REMSWITCH Study.

BACKGROUND AND AIMS: We assessed the effectiveness of switching from intravenous to subcutaneous infliximab in patients with inflammatory bowel diseases (IBDs) treated with or without intensified intravenous regimen. METHODS: In this multicenter observational study, IBD patients in clinical remission (partial Mayo score ≤2 or Harvey-Bradshaw index ≤4) were switched to a unique dose of subcutaneous infliximab (120 mg every other week). Pharmacological and biological data were collected at baseline, visit 1 (4-8 weeks postswitch), visit 2 (8-16 weeks postswitch), and visit 3 (16-24 weeks postswitch). Relapse was defined as clinical relapse or fecal calprotectin increase ≥150 µg/g compared with baseline. RESULTS: Among 184 eligible patients, 72.3% (n = 133 of 184) agreed to switch to subcutaneous infliximab. At visit 3, a relapse occurred in 10.2% (n = 6 of 59), 7.3% (n = 3 of 38), 16.7% (n = 3 of 18), and 66.7% (n = 10 of 15) (P < .001) of patients receiving 5 mg/kg every 8 weeks, 10 mg/kg every 8 weeks, 10 mg/kg every 6 weeks, and 10 mg/kg every 4 weeks, respectively. Dose escalation to 240 mg every other week led to recapture clinical remission in 93.3% (n = 14 of 15). Infliximab serum levels increased after the switch (P < .0001) except for patients receiving 10 mg/kg every 4 weeks. In multivariable analysis, 10 mg/kg every 4 weeks regimen (odds ratio, 12.4; 95% confidence interval, 1.6-98.4; P = .017) and fecal calprotectin >250 µg/g at baseline (odds ratio, 5.4; 95% confidence interval, 1.1-27.6; P = .042) had a higher risk of relapse as well as reduced (41.7%) or stable (36.8%) infliximab serum levels between baseline and visit 1 compared with increased serum levels (12.7%) (P = .020 and P = .019, respectively). Patients' acceptability (10-point scale) was improved by the switch (6.9 ± 1.6 vs 8.6 ± 1.4; P < .0001). No severe adverse event was reported. CONCLUSIONS: Switching from intravenous to subcutaneous infliximab 120 mg every other week is safe and well accepted, leading to a low risk of relapse in IBD patients except for those receiving 10 mg/kg every 4 weeks requiring 240 mg every other week.

Comparison of short- and long-term effectiveness between ustekinumab and vedolizumab in patients with Crohn's disease refractory to anti-tumour necrosis factor therapy.

BACKGROUND: The best option between vedolizumab and ustekinumab after anti-tumour necrosis factor (TNF) failure remains unclear in Crohn's disease. AIMS: To compare the short- and long-term effectiveness of vedolizumab and ustekinumab in Crohn's disease patients with prior anti-TNF exposure. METHODS: All Crohn's disease patients treated with ustekinumab or vedolizumab after exposure to at least one anti-TNF agent were included from two referral centres. Primary endpoint was corticosteroid-free clinical remission defined as Crohn's disease activity index <150 at week 54. Deep remission (corticosteroid-free clinical remission and faecal calprotectin <100 µg/g) was assessed at week 14. Propensity-matched analyses were applied to make the two groups comparable. RESULTS: Overall, 312 patients (ustekinumab = 224 and vedolizumab = 88) were included. After propensity score analysis, ustekinumab was more effective to achieve corticosteroid-free clinical remission at week 54 (49.3% vs 41.2%, P = 0.04) and deep remission at Week 14 (25.9% vs 3.8%, P = 0.02) than vedolizumab. The rate of primary nonresponders (6.7% vs 14.8%, P = 0.034) and the long-term risk of drug discontinuation due to therapeutic failure (HR = 1.53 [1.04-2.07], P = 0.029) were lower in patients treated with ustekinumab compared with vedolizumab. Predictors of ustekinumab failure were complicated phenotype (odds ratio [OR] = 2.35 [1.31-4.22]; P = 0.004) and anti-TNF primary non-response (OR = 2.55 [1.27-5.12]; P = 0.008). We did not find any predictor of corticosteroid-free clinical remission in patients treated with vedolizumab. Vedolizumab was less effective than ustekinumab in patients >35 years old (OR = 0.41 [0.19-0.87]), with noncomplicated phenotype (OR=0.42 [0.18-0.96]), no prior bowel resection (OR = 0.49 [0.24-0.96]), and no steroids at baseline (OR=0.47 [0.23-0.97]). CONCLUSION: Ustekinumab was more effective to achieve early and long-term effectiveness than vedolizumab in Crohn's disease patients who previously failed response to anti-TNF agents.

Transmural healing and MRI healing are associated with lower risk of bowel damage progression than endoscopic mucosal healing in Crohn's disease.

BACKGROUND: Endoscopic mucosal healing is the current therapeutic target in Crohn's disease. However, transmural healing could lead to better outcomes. AIMS: To assess whether transmural healing or magnetic resonance imaging (MRI) healing are better therapeutic targets than endoscopic mucosal healing to predict long-term improved outcome in Crohn's disease METHODS: From our MRI database, we retrospectively identified all Crohn's disease patients who had MRI and colonoscopy within a 3-month interval (median interval = 17.5 days). Four groups were considered: endoscopic mucosal healing (no ulceration or aphthoid erosion), MRI healing (no MRI signs of inflammation and no complication), transmural healing (combination of endoscopic and MRI healing) or no healing. Outcomes were time to surgery, bowel damage progression, hospitalisation, major outcomes (one of the three previous endpoints) and Crohn's disease-related drug discontinuation. Results were expressed in multivariable analyses adjusted on potential confounders (hazard ratio (HR) [95% confidence interval]). RESULTS: Among 154 patients with Crohn's disease, 51.9% (80/154), 10.4% (16/154), 19.5% (30/154) and 18.2% (28/154) achieved no healing, endoscopic mucosal healing, MRI healing and transmural healing, respectively. Transmural healing (HR = 0.05 [0.00-0.40], P = 0.002) and MRI healing (HR = 0.09 [0.00-0.47], P = 0.005) were associated with lower risk of bowel damage progression than endoscopic mucosal healing. In addition, achieving transmural healing or MRI healing reduced the risk of experiencing major outcomes compared to endoscopic mucosal healing (HR = 0.28 [0.00-0.74], P = 0.01). Patients with transmural healing also had a decreased risk of relapse-related drug discontinuation (HR = 0.35 [0.13-0.95], P = 0.039) compared to those with endoscopic mucosal healing. CONCLUSION: Transmural healing and MRI healing are associated with lower risk of bowel damage progression than endoscopic mucosal healing and could be considered as better therapeutic targets in Crohn's disease.

Phase 3, Multicenter Open-Label study to investigate the efficacy of elbasvir and grazoprevir fixed-dose combination for 8 weeks in treatment-naïve, HCV GT1b-infected patients, with non-severe fibrosis.

BACKGROUND: Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of 8 weeks fixed-dose combination of grazoprevir-elbasvir in treatment-naïve patients, with non-severe fibrosis. METHODS: HCV mono-infected and treatment naïve patients with non-severe fibrosis (Fibroscan® <9.5 kPa and Fibrotest®  < 0.59) were enrolled in a study which included 117 patients. Genotyping by sequencing identified five patients with non-1b genotype (two GT1a, one GT1h, one GT1e and one GT1l). Thus, we included in the final analysis 112 GT1b patients. The primary end point was the proportion of patients with HCVRNA below the lower limit of quantification 12 weeks after treatment (SVR12). FINDINGS: Mean age was 54 ± 13 years, 31% were men and viral load was higher than 800.000 IU/mL in 70 of 112 patients (63%). Using Fibroscan® , 100 had F0-1 fibrosis score. FIB-4 lower than 1.45 and APRI less than 1 was found in 74/112 (66%) and 107/112 (95%) patients respectively. Relapse occurred in three patients by week 12. These three patients had a viral load higher than 6 million IU/mL and NS5A Y93H RAS (resistance-associated substitution). Then, modified intention-to-treat SVR12 for patients with genotype 1b was 109/112 (97%). By week 24; five relapses were observed and all had the Y93H RAS at relapse. SVR12 was achieved in 100% of patients with a baseline viral load below 6 million and decreased to 98% (98/100) by follow-up week 24. INTERPRETATION: Naïve patients with genotype 1b and non-severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir-elbasvir for 8 weeks.

Vedolizumab Therapy is Ineffective for Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A GETAID Multicentre Cohort Study.

BACKGROUND: Whether vedolizumab may be effective as a treatment for primary sclerosing cholangitis [PSC] in patients with inflammatory bowel disease [IBD] remains controversial. METHODS: We performed a retrospective observational study of consecutive patients with IBD and PSC, treated with vedolizumab for at least 30 weeks in 22 centres of GETAID from January 2015 to June 2016. The outcomes included a decrease in the serum alkaline phosphatase [ALP] concentration of at least 50% from baseline to Week 30 or 54, a change in any serum liver enzymes concentrations, and an assessment of the efficacy and safety of vedolizumab in IBD. RESULTS: Among 75 patients with active IBD and PSC treated with vedolizumab, 21 patients discontinued vedolizumab before Week 30 [due to lack of efficacy in 19 and malignancy in two patients]. In the remaining 54 patients, a decrease in the serum ALP concentration of at least 50% from baseline to Weeks 30 and 54 was observed in four [7%] and four [11%] patients, respectively. No significant change was observed in serum liver enzyme concentrations at week 30 or 54. After a median follow-up period of 19.4 [14.0-29.9] months, nine cases of digestive neoplasia [colorectal neoplasia in seven and cholangiocarcinoma in two] were reported. CONCLUSIONS: In patients with IBD and PSC, vedolizumab did not improve serum liver enzyme concentrations at week 30 or 54. Nine cases of digestive cancer occurred during the follow-up period, confirming the need for a tight surveillance programme in this population.

Bowel wall healing assessed using magnetic resonance imaging predicts sustained clinical remission and decreased risk of surgery in Crohn's disease.

BACKGROUND: Endoscopic mucosal healing is considered as the best therapeutic target in Crohn's disease (CD) as it is associated with better long-term outcomes. We investigated whether bowel wall healing (BWH) assessed using magnetic resonance imaging (MRI) could predict favorable outcomes and could be a potential therapeutic target. METHODS: We performed a post hoc analysis from two prospective studies (n = 174 patients). All the patients with previous objective signs of bowel inflammation and assessed by MRI for therapeutic efficacy had a standardized and blinded evaluation, and underwent MRI. Complete BWH was defined as no segmental MaRIA > 7 or no segmental Clermont score > 8.4 and BWH as no segmental MaRIA > 11 or no segmental Clermont score > 12.5. Clinical corticosteroid-free remission (CFREM) was defined as no reappearance or worsening of clinical manifestation leading to therapeutic modification, hospitalization or CD-related surgery. Multivariate analyses were performed including all the relevant parameters. RESULTS: Overall, 63 patients with CD were included (mean follow-up = 4.8 ± 3.1 semesters). In multivariate analysis (n = 303 semesters), complete BWH or BWH was associated with sustained CFREM according to MaRIA [OR = 4.42 (2.29-26.54); p = 0.042 and OR = 3.43 (1.02-27.02); p = 0.047, respectively] or Clermont score [OR = 3.09 (1.01-12.91); p = 0.049 and OR = 3.88 (1.40-13.80); p = 0.036, respectively]. In multivariate analysis (n = 63 patients), complete BWH or BWH was associated with decreased risk of surgery using MaRIA [HR = 0.16 (0.043-0.63); p = 0.008 and HR = 0.24 (0.07-0.77); p = 0.017, respectively] or Clermont score [HR = 0.24 (0.07-0.78); p = 0.016 and HR = 0.23 (0.07-0.76); p = 0.016, respectively]. CONCLUSIONS: MRI endpoints are predictive of favorable outcomes after medical therapy and could be used as therapeutic target in daily practice and clinical trials.

Faecal calprotectin and magnetic resonance imaging in detecting Crohn's disease endoscopic postoperative recurrence.

AIM: To assess magnetic resonance imaging (MRI) and faecal calprotectin to detect endoscopic postoperative recurrence in patients with Crohn's disease (CD). METHODS: From two tertiary centers, all patients with CD who underwent ileocolonic resection were consecutively and prospectively included. All the patients underwent MRI and endoscopy within the first year after surgery or after the restoration of intestinal continuity [median = 6 mo (5.0-9.3)]. The stools were collected the day before the colonoscopy to evaluate faecal calprotectin level. Endoscopic postoperative recurrence (POR) was defined as Rutgeerts' index ≥ i2b. The MRI was analyzed independently by two radiologists blinded from clinical data. RESULTS: Apparent diffusion coefficient (ADC) was lower in patients with endoscopic POR compared to those with no recurrence (2.03 ± 0.32 vs 2.27 ± 0.38 × 10-3 mm²/s, P = 0.032). Clermont score (10.4 ± 5.8 vs 7.4 ± 4.5, P = 0.038) and relative contrast enhancement (RCE) (129.4% ± 62.8% vs 76.4% ± 32.6%, P = 0.007) were significantly associated with endoscopic POR contrary to the magnetic resonance index of activity (MaRIA) (7.3 ± 4.5 vs 4.8 ± 3.7; P = 0.15) and MR scoring system (P = 0.056). ADC < 2.35 × 10-3 mm²/s [sensitivity = 0.85, specificity = 0.65, positive predictive value (PPV) = 0.85, negative predictive value (NPV) = 0.65] and RCE > 100% (sensitivity = 0.75, specificity = 0.81, PPV = 0.75, NPV = 0.81) were the best cut-off values to identify endoscopic POR. Clermont score > 6.4 (sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74), MaRIA > 3.76 (sensitivity = 0.61, specificity = 0.82, PPV = 0.73, NPV = 0.74) and a MR scoring system ≥ MR1 (sensitivity = 0.54, specificity = 0.82, PPV = 0.70, and NPV = 0.70) demonstrated interesting performances to detect endoscopic POR. Faecal calprotectin values were significantly higher in patients with endoscopic POR (114 ± 54.5 µg/g vs 354.8 ± 432.5 µg/g; P = 0.0075). Faecal calprotectin > 100 µg/g demonstrated high performances to detect endoscopic POR (sensitivity = 0.67, specificity = 0.93, PPV = 0.89 and NPV = 0.77). CONCLUSION: Faecal calprotectin and MRI are two reliable tools to detect endoscopic POR in patients with CD.

Does Portopulmonary Hypertension Impede Liver Transplantation in Cirrhotic Patients? A French Multicentric Retrospective Study.

BACKGROUND: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension associated with portal hypertension. Its presence is a major stake for cirrhotic patients requiring liver transplantation (LT), with increased postoperative mortality and unpredictable evolution after transplantation. The aim was to study outcomes after liver transplantation in patients with portopulmonary hypertension and to identify factors associated with normalization of pulmonary hypertension. METHODS: Patients with portopulmonary hypertension who underwent LT between 2008 and 2016 in 8 French centers were retrospectively included. Pulmonary artery pressure was established by right heart catheterization before and after LT. Primary endpoint was the normalization of pulmonary artery pressure after LT. RESULTS: Twenty-three patients who received liver transplant between 2008 and 2016 were included. Two (8.7%) patients died in the immediate posttransplant period from right heart failure. With appropriate vasoactive medical treatment and LT, pulmonary arterial pressure was normalized in 14 patients (60.8%), demonstrating recovery from portopulmonary hypertension. In univariate analysis, the use of vasoactive combination therapy was the only prognostic factor for pulmonary arterial hypertension normalization after LT. CONCLUSIONS: Treatment of portopulmonary hypertension with a combination of vasoactive drugs allows LT with acceptable postoperative cardiovascular-related mortality and normalization of pulmonary hypertension in the majority of the patients.

Magnetic resonance index of activity (MaRIA) and Clermont score are highly and equally effective MRI indices in detecting mucosal healing in Crohn's disease.

BACKGROUND: Magnetic resonance index of activity (MaRIA) and Clermont score are currently the two main MRI indices that have been validated compared to endoscopy in Crohn's disease (CD). AIMS: To compare the accuracy of MaRIA and Clermont score in assessing CD mucosal healing. METHODS: Fourty-four CD patients underwent prospectively and consecutively MRI and colonoscopy. RESULTS: Considering 207 segments, MaRIA>7 and Clermont score>8.4 demonstrated substantial accuracy to detect endoscopic ulcerations (73.9% and 74.0%, respectively) and presented with high specificity (82.1% and 81.3%) and high negative predictive value (NPV) (82.1% and 82.4%) for MaRIA and Clermont score, respectively. The sensitivity for detecting deep ulcerations was 90.9% for both MaRIA>11 and Clermont score>12.5, with a specificity of 82.0% and 80.0%, respectively. Among 44 patients, deep MRI remission predicted mucosal healing with specificity=85.3% and NPV=85.3% according to Barcelona criteria (no segmental MaRIA>7), and specificity=88.2% and NPV=85.7% according to Clermont criteria (no segmental Clermont score>8.4). In addition, MRI remission predicted mucosal healing with specificity=76.5% and NPV=86.7% according to Barcelona criteria (no segmental MaRIA>11), and specificity=79.4% and NPV=84.4% according to Clermont criteria (no segmental Clermont score>12.5). CONCLUSION: MaRIA and Clermont score are equally effective in detecting CD endoscopic ulcerations supporting their use as therapeutic endpoints.