Valentina Fazio

Adalimumab Is More Effective Than Azathioprine and Mesalamine at Preventing Postoperative Recurrence of Crohn's Disease: A Randomized Controlled Trial

OBJECTIVES:Postsurgical recurrence of Crohns disease (CD) is very frequent and, to date, only infliximab has been shown to be useful in preventing it. The efficacy of adalimumab (ADA) is poorly known. We evaluated whether the administration of ADA after resective intestinal surgery reduces postoperative CD recurrence.METHODS:We randomly assigned 51 patients with CD who had undergone ileocolonic resection to receive after 2 weeks from surgery ADA at the dose of 160/80/40 mg every two weeks, azathioprine (AZA) at 2 mg/kg/day, or mesalamine at 3 g/day, and they were followed up for 2 years. The primary end point was the proportion of patients with endoscopic and clinical recurrence. Secondary end point was the assessment of quality of life by means of a previously validated questionnaire.RESULTS:The rate of endoscopic recurrence was significantly lower in ADA (6.3%) compared with the AZA (64.7%; odds ratio (OR)=0.036 (95% confidence interval (CI) 0.004–0.347)) and mesalamine groups (83.3%; OR=0.013 (95% CI 0.001–0.143)). There was a significantly lower proportion of patients in clinical recurrence in the ADA group (12.5%) compared with the AZA (64.7%; OR=0.078 (95% CI 0.013–0.464)) and mesalamine groups (50%; (OR=0.143 (95% CI 0.025–0.819)). The quality of life was higher in the ADA (202) than in the AZA (90; OR=0.028 (95% CI 0.004–0.196)) and mesalamine groups (98; OR=0.015 (95% CI 0.002–0.134)).CONCLUSIONS:The administration of ADA after intestinal resective surgery was greatly effective in preventing endoscopic and clinical recurrence of CD. Further larger studies are necessary to confirm the therapeutic advantage and to show the economic implications of biologic therapy in this field.

Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease.

Aliment Pharmacol Ther 2011; 34: 476–486

Activating NK cell receptor expression/function (NKp30, NKp46, DNAM‐1) during chronic viraemic HCV infection is associated with the outcome of combined treatment

Specific NK cell killer inhibitory receptor (KIR):HLA haplotype combinations have been associated with successful clearance of acute and chronic HCV infection. Whether an imbalance of activating NK cell receptors also contributes to the outcome of treatment of chronic HCV infection, however, is not known. We studied peripheral NK cell phenotype and function in 28 chronically viraemic HCV genotype I treatment‐naïve patients who underwent treatment with pegylated IFN‐α and ribavirin. At baseline, chronically infected patients with sustained virological response (SVR) had reduced CD56brightCD16+/− cell populations, increased CD56dullCD16+ NK cell proportions, and lower expression of NKp30, DNAM‐1, and CD85j. Similarly, reduced NK cell IFN‐γ production but increased degranulation was observed among nonresponding (NR) patients. After treatment, CD56brightCD16+/− NK cell numbers increased in both SVR and NR patients, with a parallel significant increase in activating NKp30 molecule densities in SVR patients only. In vitro experiments using purified NK cells in the presence of rIL‐2 and IFN‐α confirmed upregulation of NKp30 and also of NKp46 and DNAM‐1 in patients with subsequent SVR. Thus, differences in patient NK cell receptor expression and modulation during chronic HCV‐1 infection are associated with subsequent outcome of standard treatment. Individual activating receptor expression/function integrates with KIR:HLA genotype carriage to determine the clearance of HCV infection upon treatment.

Clinical Trial: The Association Between Rifaximin And Partially Hydrolyzed Guar Gum Is More Effective Than Rifaximin Alone In Eradicating SIBO

Aliment Pharmacol Ther 2010; 32: 1000–1006

Peripheral blood cytopaenia limiting initiation of treatment in chronic hepatitis C patients otherwise eligible for antiviral therapy.

In patients with chronic hepatitis C virus (HCV) infection, the presence of peripheral blood cytopaenia may represent an obstacle to pegylated interferon and ribavirin treatment.

Low serum trough levels are associated with post-surgical recurrence in Crohn's disease patients undergoing prophylaxis with adalimumab

BACKGROUND Whether therapeutic drug monitoring of biologic therapy can predict the efficacy of adalimumab to prevent postoperative Crohns disease recurrence is unknown. AIM To investigate whether adalimumab trough levels and anti-adalimumab antibodies correlate with endoscopic and clinical outcomes in a series of patients treated with prophylactic adalimumab monotherapy after resective surgery. METHODS Post hoc analysis of a randomized, mesalamine-controlled trial. Adalimumab trough levels and antibodies were analysed every 8 weeks for 2 years using an homogeneous mobility shift assay. RESULTS At two years, 1/6 patient had clinical recurrence and 1/6 patient had endoscopic and clinical recurrence. At baseline (9.5 vs. 14.4 mcg/mL) and during follow-up [7.5 (4.4-9.8) vs. 13.9 (8.9-23.6)mcg/mL, p<0.01], median adalimumab trough levels in patients with clinical or endoscopic recurrence were lower than in those who maintained remission. Persistent antibodies-against-adalimumab were detected in the patient with both endoscopic and clinical recurrence. CONCLUSION Measurement of adalimumab trough levels and anti-adalimumab antibodies after surgery could be useful to further reduce postoperative recurrence.

Positive PET in a Patient With Esophageal Leiomyoma

A 50-year-old man undergoing treatment with 6-thioguanine for ulcerative colitis was admitted to the gastroenterology unit with suspected sinusoidal obstruction syndrome (SOS). Clinical diagnosis, made according to Seattle modified criteria and Baltimore criteria, was supported by magnetic resonance imaging (MRI) showing a diffuse patchy pattern in the portal phase (left, panel a), the “clover-like sign,” in which liver parenchyma surrounding the main hepatic veins shows normal enhancement compared with the rest of the patchy enhanced area of liver (left, panel b), paraumbilical vein patency (left, panel c), and gallbladder wall thickening (left, panel d). Six months after 6-thioguanine was stopped, MRI showed complete resolution of the SOS; in particular, the patchy pattern disappeared (right, panel a), the hepatic veins were enhanced (right, panel b), the paraumbilical vein disappeared (right, panel c), and the gallbladder wall was normal (right, panel d).

Erratum: Positive PET in a Patient With Esophageal Leiomyoma.

This corrects the article DOI: 10.1038/ajg.2016.205