Tight control using fecal calprotectin and early disease intervention increase the rates of transmural remission in Crohn's disease.

BACKGROUND: Increasing evidence supports the use of transmural remission as a treatment target in Crohn's disease (CD), but it is seldom achieved in clinical practice. Tight monitoring of inflammation using fecal calprotectin with reactive treatment escalation may potentially improve these results. AIMS: To evaluate if treatment escalation based on fecal calprotectin can improve the rates of transmural remission in CD. The influence of the timing of intervention on this strategy was also evaluated. METHODS: Retrospective cohort study including 256 CD patients with 2 consecutive assessments by MRI-enterography and colonoscopy and with regular monitoring using fecal calprotectin. For each occurrence of an elevated fecal calprotectin (≥250 µg/g), we evaluated whether a reactive adjustment of medical treatment was performed. The ratio of treatment escalation/elevated fecal calprotectin was correlated with the chances of reaching transmural remission. Early disease was defined as disease duration <18 months without previous exposure to immunomodulators and biologics. RESULTS: After a median follow-up of 2 years (IQR 1-4), 61 patients (23.8%) reached transmural remission. Ratios of escalation ≥50% resulted in higher rates of transmural remission (34.2% vs. 15.1%, p < 0.001). The effect was more pronounced in patients with early disease (50.0% vs. 12.0%, p = 0.003). In multivariate analysis, a treatment escalation ratio ≥50% (OR 3.46, 95% CI 1.67-7.17, p = 0.001) and early disease intervention (OR 3.24, 95% CI 1.12-9.34, p = 0.030) were independent predictors of achieving transmural remission. CONCLUSION: Tight-monitoring and reactive treatment escalation increase the rates of transmural remission in CD. Intervention in early disease further improves these results.

Transmural remission improves clinical outcomes up to 5 years in Crohn's disease.

INTRODUCTION: Evidence supporting transmural remission (TR) as a long-term treatment target in Crohn's disease (CD) is still unavailable. Less stringent but more reachable targets such as isolated endoscopic (IER) or radiologic remission (IRR) may also be acceptable options in the long-term. METHODS: Multicenter retrospective study including 404 CD patients evaluated by magnetic resonance enterography and colonoscopy. Five-year rates of hospitalization, surgery, use of steroids, and treatment escalation were compared between patients with TR, IER, IRR, and no remission (NR). RESULTS: 20.8% of CD patients presented TR, 23.3% IER, 13.6% IRR and 42.3% NR. TR was associated with lower risk of hospitalization (odds-ratio [OR] 0.244 [0.111-0.538], p < 0.001), surgery (OR 0.132 [0.030-0.585], p = 0.008), steroid use (OR 0.283 [0.159-0.505], p < 0.001), and treatment escalation (OR 0.088 [0.044-0.176], p < 0.001) compared to no NR. IRR resulted in lower risk of hospitalization (OR 0.333 [0.143-0.777], p = 0.011) and treatment escalation (OR 0.260 [0.125-0.540], p < 0.001), while IER reduced the risk of steroid use (OR 0.442 [0.262-0.745], p = 0.002) and treatment escalation (OR 0.490 [0.259-0.925], p = 0.028) compared to NR. CONCLUSIONS: TR improved clinical outcomes over 5 years of follow-up in CD patients. Distinct but significant benefits were seen with IER and IRR. This suggests that both endoscopic and radiologic remission should be part of the treatment targets of CD.

Proactive infliximab is more effective than vedolizumab in inducing fecal calprotectin remission in inflammatory bowel disease.

BACKGROUND: Current evidence suggests vedolizumab (VDZ) may be as effective as Infliximab (IFX) in inflammatory bowel disease. It is unknown if proactive therapeutic drug monitoring (PTDM) of IFX may improve these results. METHODS: Case-control study including consecutive patients with primary response to conventional IFX (n = 70), proactive IFX (n = 148), and VDZ (n = 95). PTDM was performed at week 14 and every other infusion, aiming at a trough level between 5 and 10 µg/ml. The primary outcome was fecal calprotectin (Fc) remission (<250 µg/g) at 1 year of treatment. Secondary outcomes included Fc remission at week 14 (proactive IFX/VDZ), clinical remission, treatment discontinuation, hospitalization, and surgery at 1-year of follow-up. RESULTS: Proactive IFX was superior to conventional IFX and VDZ in inducing Fc remission at 1-year (69.4% vs 47.1% vs 37.9%, p = .003 and p < .001). Results remained significant in biologic naïve patients (70.8% vs 44.4% vs 51.4%, p = .001 and p = .043) but comparisons between conventional IFX and VDZ were not significant (p = .265 and p = .664). In multivariate analysis correcting for prior biologic exposure, proactive IFX was more effective than conventional IFX (OR 2.480 95%CI [1.367-4.499], p = .003) and VDZ (OR 3.467 95%CI [1.578-7.617], p = .002) in inducing Fc remission. Amongst secondary outcomes, only clinical remission was significant between proactive IFX and VDZ in the overall cohort (80.4% vs 55.8%, p < .001) and in biologic naïve patients (80.2% vs 62.9%, p = .043). Fc remission at 1-year was associated with better results in most secondary outcomes. CONCLUSION: Proactive IFX was superior to VDZ in inducing Fc remission at 1-year, which was associated with improved clinical outcomes.SUMMARYCurrent evidence suggests that vedolizumab may be as effective as Infliximab in the treatment of patients with inflammatory bowel disease.There have been no studies comparing vedolizumab with proactively optimized Infliximab based on trough levels.We confirm that conventional IFX is as effective as vedolizumab but proactive IFX appears superior to vedolizumab in inducing fecal calprotectin remission.Fecal calprotectin remission associates with better clinical outcomes.

Proactive therapeutic drug monitoring is more effective than conventional management in inducing fecal calprotectin remission in inflammatory bowel disease.

BACKGROUND: Proactive therapeutic drug monitoring (pTDM) may improve treatment outcomes in inflammatory bowel disease. AIMS AND METHODS: We compared 135 patients following a prospective pTDM protocol aiming at an infliximab trough level (IFXTL) between 5 and 10 µg/ml with sequential measurements of Fc, with 108 patients from a retrospective group under conventional management. We evaluated the rates of Fc remission (<250 µg/g) and other clinical outcomes at 2-year of follow-up. RESULTS: pTDM associated with higher rates of Fc remission (69.6% vs. 50.0%; P = 0.002), and steroid-free clinical remission (78.4% vs. 55.2%, P = 0.028) with a trend for clinical remission (79.3% vs. 68.5%, P = 0.075). There was no difference in treatment discontinuation (P = 0.195), hospitalization (P = 0.156), and surgery (P = 0.110). Higher IFXTL associated with Fc remission at week 14 (6.59 vs. 2.96 µg/ml, P < 0.001), and at the end of follow-up (8.10 vs. 5.03 µg/ml, P = 0.001). In patients reaching Fc remission after week 14, IFXTL increased from week 14 to the end of follow-up (2.71 vs. 8.54 µg/ml, P < 0.001). Fc remission associated with higher rates of clinical (85.8% vs. 56.8% P < 0.001) and steroid-free clinical remission (86.9% vs. 50.0% P < 0.001), lower IFX discontinuation (8.8% vs. 36.8%, P < 0.001), and hospitalization (13.5% vs. 33.7%, P < 0.001), without significance for surgery (6.1% vs. 12.6%, P = 0.101). CONCLUSION: pTDM was more effective than conventional management in inducing Fc remission which was associated with improved outcomes.

Proactive Infliximab Drug Monitoring Is Superior to Conventional Management in Inflammatory Bowel Disease.

BACKGROUND: Increasing evidence supports the use of reactive therapeutic drug monitoring (TDM) in Crohn's disease (CD) and ulcerative colitis (UC) following secondary loss of response. It is still unknown if proactive TDM can improve clinical outcomes. METHODS: Consecutive patients completing infliximab (IFX) induction therapy were prospectively allocated into a proactive TDM protocol (pTDM). Before the fourth infusion and every 2 infusions, IFX trough levels and antidrug antibodies were measured using a drug-sensitive assay (Theradiag, Lisa Tracker). Treatment was proactively escalated aiming at an IFX trough level between 3 and 7 ug/mL (CD) and 5 and 10 ug/mL (UC). A retrospective cohort treated with IFX but without TDM served as the reference group. End points included the need for surgery, hospitalization, treatment discontinuation, and mucosal healing at 2 years of follow-up. RESULTS: Two hundred five patients were included, 56 in the proactive regimen. Treatment escalation was more common in pTDM patients (76.8% vs 25.5%; P < 0.001), who also required less surgery (8.9% vs 20.8%; P = 0.032) and presented higher rates of mucosal healing (73.2% vs 38.9%; P < 0.0001). Proactive TDM significantly decreased the odds of reaching any unfavorable outcome (odds ratio, 0.358; 95% confidence interval, 0.188-0.683; P = 0.002). CONCLUSIONS: Proactive TDM is associated with fewer surgeries and higher rates of mucosal healing than conventional non-TDM-based management.

Predicting the Course of Disease in Hospitalized Patients With Acute Severe Ulcerative Colitis.

BACKGROUND: Up to one-third of patients with acute severe ulcerative colitis (ASUC) will fail intravenous steroid (IVS) treatment, requiring rescue therapy with cyclosporin (Cys), infliximab (IFX), or colectomy. Although several scores for predicting response to IVS exist, formal comparison is lacking. METHODS: We performed a single-center retrospective analysis including 489 patients with ulcerative colitis. In patients with ASUC, the Mayo endoscopic subscore and the Oxford, Edinburgh, and Lindgren scores were assessed. Outcomes included IVS failure, need for rescue medical therapy, and surgery. RESULTS: One hundred twelve patients presented with ASUC. Forty-two percent showed an incomplete or absent response to IVS, 28.6% received rescue therapy (22 with IFX, 10 with Cys, and 1 with sequential treatment), and 26.8% required surgery. The Lindgren score showed the highest performance in predicting IVS failure (are under the curve [AUC], 0.856; 95% confidence interval [CI], 0.784-0.928), need for medical rescue therapy (AUC, 0.826; 95% CI, 0.749-0.902), and surgery (AUC, 0.836; 95% CI, 0.712-0.960; all P < 0.01). CONCLUSIONS: In our series, the Lindgren score was superior to the Mayo, Oxford, and Edinburgh scores in predicting major clinical outcomes in ASUC.

Intraductal papillary mucinous neoplasm presenting with recurrent pancreatitis: a report of a painful 3-decade-long history.

Intraductal papillary mucinous neoplasm represents the most common pancreatic cystic neoplasm and harbours significant malignant potential. Duct obliteration can lead to recurrent episodes of pancreatic inflammation mimicking acute and chronic pancreatitis. We report a case of a patient with multiple episodes of idiopathic pancreatitis occurring over a period of three decades. Following admission with severe upper gastrointestinal bleeding, the patient was diagnosed as having invasive pancreatic adenocarcinoma. Examination of the surgical specimen confirmed an intraductal papillary mucinous neoplasm with multiple foci of invasive adenocarcinoma. This case is of significant interest, highlighting the long delay until diagnosis seen in this situation. Intraductal papillary mucinous neoplasm should be considered in the presence of recurrent acute or chronic pancreatitis of unknown aetiology.

Acute cholangitis in an old patient with Crigler-Najjar syndrome type II - a case report.

BACKGROUND: Crigler-Najjar syndrome (CN) is a very rare genetic disorder characterized by an inability to conjugate bilirubin. Contrary to CN type I, patients with CN II exhibit residual capacity to conjugate bilirubin and may present a normal life expectancy. CASE PRESENTATION: We report an unusual late diagnosis of CN type II in an 80-year-old female admitted with severe acute cholangitis. While the patient present typical clinical and radiologic signs of bile duct obstruction and cholangitis, her blood analysis showed severe unconjugated hyperbilirubinemia. Endoscopic retrograde cholangiopancreatography confirmed the diagnosis and allowed therapeutic intervention. The anatomopathologic examination of her gallbladder following cholecystectomy showed signs of chronic cholecystitis. CONCLUSION: The risk of gallstone disease may be increased in patients with CN syndrome. While unusual, we alert to this curious and potential life-threatening presentation.