Serum Levels of PCSK9 Are Increased in Patients With Active Ulcerative Colitis Representing a Potential Biomarker of Disease Activity: A Cross-sectional Study.

BACKGROUND/GOAL: Ulcerative colitis (UC) is characterized by chronic inflammation and progressive course, with potential extraintestinal complications including cardiovascular mortality. Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels have been recently recognized as biomarkers of low-grade inflammation and cardiovascular disease. The aim of our study was to evaluate PCSK9 levels in patients with UC and different degrees of disease activity. METHODS: We prospectively recruited consecutive patients with UC attending our center at the University Hospital of Padua. Demographics, clinical characteristics, and biochemical data, including PCSK9, high sensitivity C-reactive protein, and fecal calprotectin, were recorded. Moreover, endoscopic procedures were performed in all subjects. RESULTS: We included 112 patients with UC (mean age=52.62±12.84 y; 52.62% males). Patients with UC and abnormal fecal calprotectin (≥250 µg/g) and/or C-reactive protein (≥3 mg/L) had greater levels of PCSK9 compared with UC patients with normal fecal calprotectin and high sensitivity C-reactive protein ( P =0.03 and 0.005, respectively). Higher endoscopic scores in UC were characterized by greater levels of PCSK9 ( P =0.03). Furthermore, we found a positive correlation between PCSK9 levels and fecal calprotectin ( r =0.18, P =0.04), endoscopic Mayo Score ( r =0.25, P =0.007), and UC-Riley Index ( r =0.22, P =0.01). We also found a positive correlation between PCSK9 levels and both total and low-density lipoprotein cholesterol values ( P <0.05). CONCLUSIONS: Serum PCSK9 levels are increased in patients with biochemical and endoscopic evidence of active disease in UC. Further longitudinal studies are necessary to evaluate the role of PCSK9 as a potential biomarker of disease activity and cardiovascular risk in UC.

Device-assisted enteroscopy: Are we ready to dismiss the spiral?

Motorized spiral enteroscopy (MSE) is the latest advance in device-assisted enteroscopy. Adverse events related to MSE were discussed in a recent large systematic review and meta-analysis and were directly compared with those of balloon enteroscopy in a case-matched study and a randomized controlled trial. Following the real-life application of MSE, an unexpected safety issue emerged regarding esophageal injury and the technique has been withdrawn from the global market, despite encouraging results in terms of diagnostic and therapeutic yield. We conducted an Italian multicenter real-life prospective study, which was prematurely terminated after the withdrawal of MSE from the market. The primary goals were the evaluation of MSE performance (both diagnostic and therapeutic) and its safety in routine endoscopic practice, particularly in the early phase of introduction in the endoscopic unit. A subanalysis, which involved patients who underwent MSE after unsuccessful balloon enteroscopy, demonstrated, for the first time, the promising performance of MSE as a rescue procedure. Given its remarkable performance in clinical practice and its potential role as a backup technique following a previously failed enteroscopy, it may be more appropriate to refine and enhance MSE in the future rather than completely abandoning it.

Outcomes of Double Balloon-Enteroscopy in Elderly vs. Adult Patients: A Retrospective 16-Year Single-Centre Study.

Background and Aim: Double-balloon enteroscopy (DBE) is a well-established procedure for direct visualisation of the entire small bowel mucosa, and, in contrast with other imaging techniques, allows to perform biopsies and therapeutic interventions. The aim of this study was to evaluate the indications, diagnostic yield, therapeutic yield, and complications of DBE in a cohort of consecutive patients according to patients' age. Methods: We conducted a retrospective study of consecutive patients who underwent DBE in our endoscopy unit between January 2006 and December 2021. Results: A total of 387 consecutive patients who underwent 460 DBE procedures were included. Mean age of the patients was 63 years. The overall diagnostic yield was 67.6%; vascular lesions were the predominant endoscopic findings (31.5%), followed by polyps or neoplastic masses (17.6%). Older patients (≥65 years) showed statistically higher rates of clinically relevant findings than adult patients (18-65 years) (p = 0.001). Crohn's disease and polyps or neoplastic masses were more frequent in the younger group (p = 0.009 and p = 0.066, respectively), while vascular lesions and non-specific inflammation were the most common findings in the older group (p < 0.001 and p < 0.001, respectively). The therapeutic intervention rate was 31.7%. Rates of endoscopic treatment were significantly higher in the older group (p < 0.001). Total complications occurred in five procedures (1.1%). Conclusion: In clinical practice, DBE is an efficient diagnostic and therapeutic tool with a high safety profile, particularly in the elderly population.

Serum oncostatin M predicts mucosal healing in patients with inflammatory bowel diseases treated with anti-TNF, but not vedolizumab.

BACKGROUND: Oncostatin M was recently highlighted as a promising biomarker for therapeutic effectiveness in inflammatory bowel diseases (IBD), with particular regard for infliximab. The primary aim was to evaluate the ability of serum oncostatin M to predict endoscopic response to different drugs in IBD. METHODS: We selected two different cohorts of patients with IBD, treated with anti-TNF (infliximab and adalimumab) or with vedolizumab. Therapeutic response was evaluated at week 54 in terms of mucosal healing. Serum oncostatin M and C-reactive protein were measured at baseline; fecal calprotectin was measured at baseline and after 14 weeks of treatment. We evaluated the association of these biomarkers with mucosal healing at week 54. RESULTS: Among 66 patients treated with anti-TNFs and 68 treated with vedolizumab, 35 and 31 attained mucosal healing, respectively. Mucosal healing at 54 weeks was significantly associated with low oncostatin M levels at baseline in the anti-TNF cohort; the diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing was 0.91 (95% CI 0.84 to 0.99) in the anti-TNF cohort and 0.56 (95% CI 0.43 to 0.70, P < 0.001) in the vedolizumab cohort. Mucosal healing was also associated with low fecal calprotectin levels at week 14 in both cohorts. CONCLUSION: Our study suggests that serum oncostatin M is a drug-specific biomarker, since it could be used to predict therapeutic effectiveness to anti-TNFs but not to vedolizumab. Moreover, these results emphasize the utility of serum oncostatin M measurement in patients treated with anti-TNF.

Switching from Infliximab Originator to SB2 Biosimilar in Inflammatory Bowel Diseases: A Multicentric Prospective Real-Life Study.

BACKGROUND: Current literature still lacks studies evaluating the effectiveness and safety of switching from Infliximab originator to SB2 biosimilar in Inflammatory Bowel Diseases (IBDs). We aimed to verify the ability of SB2 to maintain the clinical and biochemical response induced by originator after switching. As secondary outcome, we aimed to verify safety, tolerability and immunogenicity of SB2 biosimilar compared with its IFX originator. METHODS: We prospectively enrolled all patients who switched from originator to SB2 at three Italian IBD Units from August 2018 to April 2020. We collected clinical and biochemical data at the time of switch (T0), and at the first (T1) and the second (T2) visits after switching (mean time from switching: 135 and 329 days, respectively). In addition, data regarding therapeutic drug monitoring at T0 and T1 were recorded. RESULTS: Eighty-five IBD patients (28 with Ulcerative Colitis and 57 with Crohn's Disease) were included in the study. At T1, we observed statistically significant modifications in clinical activity of disease (70 patients were in clinical remission at baseline and 60 at T1 p = 0.02), but not at T2 (p = 0.3). Fecal calprotectin values were not different both at T1 and T2 (both p = 0.9) as well as the rate of concomitant treatment with steroids (p = 0.2 and p = 0.1) or immunosuppressants (p = 0.1 and p = 1.0). Moreover, the need for therapeutic optimization from T0 to T1 and from T1 to T2 was found significant (both p = 0.01). No anti-drug antibodies were identified at T1, and no serious adverse events were recorded. CONCLUSIONS: Overall, our data show that most of the patients switching from Infliximab originator to SB2 maintain the clinical and biochemical remission for at least 1 year. Further data are necessary to understand the clinical implications of these findings in the long term.

Adalimumab biosimilars, ABP501 and SB5, are equally effective and safe as adalimumab originator.

To date, data on effectiveness and safety of Adalimumab (ADA) biosimilars in inflammatory bowel diseases (IBDs) are lacking. Therefore, we aimed to verify the ability of ABP501 and SB5 to maintain the clinical and biochemical response induced by the ADA originator, after switching to them. We prospectively analyzed data collected from 55 patients with IBD who switched to ABP501, and 25 patients with IBD who switched to SB5, from ADA originator at four IBD Units between 2018 and 2020. In addition, we included an age and sex-matched control group (n = 38) who continued ADA originator for at least two years and who did not switch to a biosimilar drug. Clinical and biochemical data (C-Reactive Protein (CRP), fecal calprotectin (FC)), concomitant steroid and/or immunosuppressant therapy at the time of the switch and after six months were collected. At six months, in the ABP501 group, we did not observe statistically significant modifications in clinical activity of disease (p = 0.09) and FC values (p = 0.90). Some patients (n = 8) needed to add steroids at six months after switching (p = 0.01), however the need for optimization was not significant between the two timepoints (p = 0.70). Finally, 14.5% patients stopped therapy after six months. Similarly, in the SB5 group we observed a stability of clinical activity and FC values (p = 0.90 and p = 0.20), and a concomitant statistically significant decrease in CRP (p = 0.03). There were no differences in steroids/immunosuppressants need or optimizing biological therapy in this group. Finally, drug survival curves of patients who switched from originator to ABP501 and those who continued ADA originator were similar (p = 0.20). Overall, biosimilar drugs seem to be as effective and safe as the originator. Further larger and longer studies are mandatory to understand the clinical implications of these findings.

Faecal microbiota transplantation in Clostridioides difficile infection: real-life experience from an academic Italian hospital.

BACKGROUND: Faecal microbiota transplantation (FMT) is a reasonable therapeutic option for the treatment of Clostridioides difficile infection (CDI) recurrent and refractory (RCDI) to therapy, but little evidence on the long-term impact of this therapy is currently available in the literature. The aim of this study was to evaluate the efficacy and safety of FMT in recurrent and refractory CDI and the modifications of the recipient's gut microbiota in the medium-long term. METHODS: This prospective study collects the clinical and laboratory data of RCDI patients treated with FMT by colonoscopy from February 2016 to October 2019. Stool samples for metagenomic analysis were collected pre-FMT at 1 week and at 6 and 12-24 months post-FMT. RESULTS: In the study period, 20 FMT procedures were performed on 19 patients. Overall, FMT was effective in 85% of treated patients. No serious adverse event was recorded. In the medium- to long-term follow up, a newly diagnosed case of collagenous colitis was observed. Post-FMT, significant changes in microbiota were observed, characterised by the transition from a low- to a greater-diversity profile. Therefore, FMT restores eubiosis and maintains it over time. CONCLUSION: FMT is a safe and effective treatment option in RCDI patients. This procedure induces profound microbiota changes that explain its high clinical efficacy.