Introduction

The therapeutic armamentarium for inflammatory bowel disease (IBD) includes several biological agents: infliximab (IFX), adalimumab (ADA), vedolizumab (VED) and ustekinumab (UST). Persistence in therapy with these drugs is not satisfactory, not only due to the loss of clinical response over time but also due to adverse events. Acute infusion reactions (AIRs) occur during or within 24 hours of the infusion. The intensity of AIRs ranges from mild (flushing, dizziness, headache, itching, rash) to severe (anaphylactic).

Aims & Methods

The primary aim of this study was to compare the prevalence rates of AIRs due to the different biological agents in a large cohort of patients with IBD and to assess risk factors for AIRs.
All reports of AIRs occurring from January 2021 to October 2023 in IBD patients treated with different biological agents (IFX, ADA, VED and UST) in a tertiary IBD center were retrospectively reviewed. The electronic records of the identified patients were checked for the type of IBD, whether Crohn's disease (CD) or ulcerative colitis (UC), type of biological agent, route of administration (intravenous or subcutaneous), concomitant immunosuppressive therapies, atopic status. Furthermore, the type of treatment for the AIRs and the subsequent therapy undertaken for IBD were also recorded.

Results

22 AIRs were recorded out of 1911 patients (1.1%). Of these, 16/550 in patients on IFX biosimilars (2.9 %), 4/590 (0.7%) in patients on ADA biosimilars, 2/318 (0.6%) in patients on VED and 0/453 (0%) in patients on UST (Table 1). The difference in the prevalence of AIR rates observed with the different biological agents was statistically significant (p<0.01). 7 of 16 post-IFX AIRs were moderate-severe, with two episodes of anaphylaxis occurring in patients with CD. The two patients treated with VED experienced only mild symptoms, and no anti-reactive treatment has been used; two mild and two moderate AIRs, respectively, have been reported among patients on ADA. 12 of 22 AIRs occurred during the induction period (from the first to the third administration). 7 of 22 patients had previous allergic reactions.

Conclusion

Our real-world data on a large population of IBD patients treated with biologic agents confirm that AIRs are rare and occur mainly in patients treated with IFX biosimilars. Most patients who experienced AIRs were atopic. Almost all patients after AIRs changed biological agents within or out of the same biological class. Further studies are necessary to confirm our results and better characterise the profile of patients at greater risk of AIRs.

Introduction

Nephrolithiasis (NL) is a common extra-intestinal complication of inflammatory bowel diseases (IBD) with significant morbidity and mortality¹. Its pathogenesis and risk factors still need to be completely elucidated. Because of intestinal malabsorption, enteric hyperoxaluria is a critical pathogenic mechanism responsible for the development of NL in IBD patients². Growing evidence has highlighted the association between gut microbiota and NL, particularly emphasising the role of some oxalate-degrading bacteria, such as Oxalobacter formigenes, representing the mainstay of the so-called “gut-kidney axis”³. More recent studies also hypothesize the involvement of urinary microbiota⁴, but no data on IBD patients are currently available. Thus, our study aims to analyse the urinary lithogenic profile in IBD patients and its relationship with gut and urinary microbiota.

Aims & Methods

Consecutive adult patients with IBD were prospectively enrolled. The presence of ileoanal pouch, ileostomy, colostomy or short-bowel syndrome were exclusion criteria. Demographic and clinical data, including previous episodes of NL, were collected. Disease activity was evaluated using Harvey-Bradshaw index for Crohn’s disease (CD) and Mayo score for ulcerative colitis (UC). All patients underwent abdominal ultrasound for NL detection. Blood tests of kidney function (notably creatinine, blood urea nitrogen, creatinine clearance, and electrolytes) were also measured, together with a 24h-urine collection for lithogenic profile analysis, including calcium oxalate relative saturation ratio (RSRCaOx). In a subgroup of patients, urinary and faecal microbiota were also analysed through 16S rRNA sequencing.

Results

48 patients (52.1% men, mean age 42.6±17.4 years) were enrolled. Twenty-five patients were affected by CD and 23 by UC and 10 presented active disease at enrollement. NL was more frequent in CD than in UC (32% vs. 13%). In CD, 24-h urinary volume was lower and 24-h oxaluria was higher than in UC. Moreover, 24-h oxaluria was higher in patients with previous or present NL. Gut microbiota analysis was performed on 22 patients, stratified based on median RSRCaOx (higher or lower than the median). Significantly different β-diversity was observed between the two groups (p =0.025) and patients with an elevated RSRCaOx showed a higher relative abundance of Bacteroidetes and a lower abundance of Firmicutes (p value <0.05). No statistically significant difference was found in urinary microbiota composition between patients with high or low levels of RSRCaOx.

Conclusion

NL is more common in CD patients, who generally present lower urine volume and higher 24-h oxaluria than UC patients. Furthermore, NL is more frequent in IBD patients with higher oxaluria levels, confirming oxalate excretion's crucial role in NL pathogenesis. Again, our study reports an association between urinary stone development and Firmicutes/Bacteroidetes imbalance in the gut microbiota, suggesting possible further studies to identify patients at higher risk of NL.

References

1. Varda BK, McNabb-Baltar J, Sood A, et al. Urolithiasis and urinary tract infection among patients with inflammatory bowel disease: a review of US emergency department visits between 2006 and 2009. Urology. 2015;85(4):764-770. doi:10.1016/j.urology.2014.12.011
2. Witting C, Langman CB, Assimos D, et al. Pathophysiology and Treatment of Enteric Hyperoxaluria. Clin J Am Soc Nephrol. 2021;16(3):487-495. doi:10.2215/CJN.08000520
3. Ticinesi A, Milani C, Guerra A, et al. Understanding the gut-kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers. Gut. 2018;67(12):2097-2106. doi:10.1136/gutjnl-2017-315734
4. Xie J, Huang JS, Huang XJ, et al. Profiling the urinary microbiome in men with calcium-based kidney stones. BMC Microbiol. 2020;20(1):41. doi:10.1186/s12866-020-01734-6

Introduction

In the years to follow we anticipate a rise in the prevalence of an aging population of inflammatory bowel disease (IBD) patients and a rise in cancer incidence. We are in urgent need of data to help us manage these patients.
We therefore followed a cohort of patients from a referral oncology hospital with prior and active cancer who received biologic therapy to control their IBD.

Aims & Methods

We first recorded data regarding inflammatory bowel disease characteristics: disease type, disease duration, disease severity, previous surgery or hospitalization and received therapy: type and duration of biologic therapy, prior use of immunosuppressants. We also recorded all available data regarding cancer disease: cancer site, stage, virus related cancer, family history of cancer, smoking status and received therapy (curative surgery, chemotherapy, hormone therapy, radiotherapy, immunotherapy). We monitored outcomes of IBD (steroid free clinical remission, IBD-related surgery or hospitalization) and outcomes of cancer (recurrence free survival, progression free survival, overall survival).
A blinded oncologist was asked to retrospectively evaluate all available data regarding cancer prognosis (stage, histology, response to therapy) and to categorize patients in 3 groups: low, intermediate or high risk to recur or progress.

Results

A total of 30 patients were included, 57 % female, median age 60 years, 60% Crohn's Disease, median disease duration 9.5 years, 26% prior IBD surgery, 33% prior azathioprine use, 36% smokers. They were treated with anti-TNF therapy (n=19) anti-integrin therapy (n=8) and anti-IL 12/23 therapy (n=4). The majority (20%) of patients had a history of hematologic malignancy (lymphomas, myeloproliferative disorders, leukemias), 13% with a virus related cancer and 66% with curative surgery. Patients were classified retrospectively as 63% low risk, 13% intermediate risk and 10% high risk. Four patients ) with active cancer (2 with lung cancer and 2 with myeloproliferative disorders) continue to receive biologic therapy for IBD and oncological therapy with no signs of progression from both diseases. All but 3 patients have remained in steroid free clinical remission: 3 had IBD-related surgery. Median follow up under biologic therapy was 5.5 years: only 2 patients showed cancer recurrence: 1 patient with breast cancer developed bone metastases and finally died, and 1 patient with colon cancer developed bladder cancer and died as well. Both patients were classified as high risk.
In both patients biologic therapy was interrupted and that resulted in administration of high-dose steroids and IBD-related hospitalizations and infections (pneumonia, C Difficile colitis).

Conclusion

In this cohort of cancer patients with IBD treated with biologics and followed up for more than 5 years the risk of cancer recurrence was low and not unexpected in oncology terms.
Biologic therapy was successful in the majority of patients and kept them off surgeries and steroids for their underlying IBD. We need more smart and innovative ways to study this particular clinical scenario in the future.

Introduction

Recently, subcutaneous vedolizumab formulation has been approved for the treatment of Inflammatory Bowel Disease. Data from randomized controlled trials on Crohn disease and ulcerative colitis report that subcutaneous vedolizumab formulation efficacy and safety were comparable to intravenous one.

Aims & Methods

The aim of our study was thus to evaluate the safety and the effectiveness of switching from intravenous to subcutaneous vedolizumab in inflammatory bowel disease patients in clinical remission.
In this prospective cohort study, we collected data on patients afferent to our center from September 2021 to April 2022. Baseline demographic characteristics, 12- and 24-weeks follow-up clinical activity and C-reactive protein levels, and adverse events were recorded. The primary endpoint was to assess combined steroid-free clinical remission plus biochemical remission at week 24.

Results

93 patients (43 Crohn disease, 50 ulcerative colitis) switched from intravenous to subcutaneous vedolizumab therapy after a median duration of intravenous treatment of 36 months [IQR 16-52]. Of note, 53.7% were previously anti-TNFα exposed and 41.9% were naive to biologics and immunosuppressors. Most of patients (94.6%) were on every 8-weeks maintenance therapy. At baseline, 80 patients (86%) were in combined remission; 93.5% of patients and 91,4% of patients reached the 12-weeks and 24-weeks follow up visit respectively. At week 24, 89.2% (n=74) patients maintained combined steroid-free clinical remission plus biochemical remission from baseline. Overall, 25 adverse events out of 23 patients were reported, mostly SARS-CoV-2 infections and injection site reactions, with further 4 recurrence episodes. Twelve patients (12.9%) discontinued subcutaneous and restarted intravenous vedolizumab.

Conclusion

Switching from intravenous to subcutaneous vedolizumab can be considered a reasonably safe and effective treatment in maintaining remission in inflammatory bowel disease patients at a 24-weeks follow-up. Additionally, this might slash healthcare costs. However, larger scale real-life studies with long-term follow-ups are needed.

Disclosure

Conflicts of interest: Daniela Pugliese received speaker fees and/or advisory board fees from AbbVie, Janssen, MSD, Pfizer and Takeda. Franco Scaldaferri received speaker fees and/or advisory board fees from, Janssen, MSD, Pfizer and Takeda, Sandoz , celltrion , ferring. Alessandro Armuzzi has received consulting/advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celgene, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda; speaker's fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Tigenix; research support from Biogen, MSD, Pfizer and Takeda. Antonio
Gasbarrini is an advisory board member for Actial Farmaceutica, Alfa Sigma, Zambon and Aboca.

Introduction

Therapeutic goals in inflammatory bowel diseases (IBD) have undergone considerable change in recent years, with a shift of focus from simply achieving clinical remission. Patient-related outcomes (PROs) have also become increasingly important as adjunctive tools in assessing the efficacy of medical therapy from the patients’ standpoint. Health-related quality of life (HRQoL) questionnaires, correlate well with disease activity and can detect meaningful clinical changes in IBD patients who either suffer a relapse of disease or achieve remission [1,2].

Aims & Methods

We aimed to assess the utility of SIBDQ in the long-term follow-up of IBD patients compared to the conventionally used markers such as clinical indices, CRP levels and endoscopic activity scores. Patients were scheduled for evaluation every 12 months, but additional evaluations were performed as required in case of worsening clinical condition. The main data collected at each study visit included clinical aspects (disease activity, on-going medication, quality of life assessement-The Short Inflammatory Bowel Disease Questionnaire), endoscopic and histological findings.

Results

In a prospective setting, 176 patients were included in the study (65 Crohn’s and 111 UC patients) , with a mean follow-up time of 16 months and 1.3 study visits per patient. Clinical activity was associated with significantly lower SIBDQ (median 4.3 vs 5.7 in those without clinical activity, p<0.001 mann whitney u) and increased inflammatory burden ( median CRP levels 1,99 mg/L vs. 7.2mg/L, p<0.001 mann whitney u). SIBDQ scores were also significantly higher in patients showing mucosal healing compared to those with active ongoing inflammation (5.8 vs 4.9, p<0.001 MWU), while inflammatory burden was also significantly different between patients with and without ongoing mucosal activity (1.6 mg/L vs 4.2 mg/L, p< 0.001 MWU). SIBDQ significantly improved over time, with a median of 4.7, 5.4 and 5.8 at visits 1, 2 and 3 respectively (p<0.001 MWU), which was also consistent with a decrease in the overall inflammatory burden in the cohort (median CRP levels of 4.2, 3.4 and 2.5 mg/L respectively).

Conclusion

Clinical activity is associated with significantly lower quality of life and increased inflammatory burden. QoL scores are significantly higher in patients showing mucosal healing compared to those with active ongoing inflammation.

References

[1] Jowett SL, Seal CJ, Barton JR, Welfare MR. The short inflammatory bowel disease questionnaire is reliable and responsive to clinically important change in ulcerative colitis. Am J Gastroenterol. 2001 Oct;96(10):2921-8.
[2] Irvine EJ^​, Zhou Q, Thompson AK.The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn's Relapse Prevention Trial. Am J Gastroenterol. 1996 Aug;91(8):1571-8.

Introduction

Infections are one of the main side effects faced by patients treated with biological agents.

Aims & Methods

Objective: We aimed to determine the rates of bacterial infections among Inflammatory Bowel Disease (IBD) patients treated with biological agents in a real-life setting.
Methods: Retrospective study based on the Clalit healthcare nationwide database, which included all patients diagnosed with IBD between 1999 and 2022. Data on bacterial infections were collected for patients treated with a biologic agent (Anti_TNF, Vedolizumab and Ustekinumab) and were compared to all other IBD patients during the corresponding timeframe.
Data regarding demographics, bacterial infection events, and mortality were collected. Data were collected using the MdClone platform from the largest Health Maintenance Organization, “Clalit” in Israel.

Results

5523 IBD patients treated with Anti-TNF were compared to 29,598 patients not treated with Anti-TNF. Patients treated with Anti-TNF were younger, age 35.62±14.29 compared to 47.06±19.49 years. Anti-TNF patients had higher rates of respiratory tract infection (36.2% vs 31.2%), genitourinary system infection, 26.7% vs 23.7%, gastrointestinal tract infection (31.8% vs 21.6%), skin infection (22.5% vs 14.3%) and Ear, Nose, throat infection (31.5% vs 24.2%). 2220 patients treated with Vedolizumab compared to 35,100 not treated with Vedolizumab, patients treated with Vedolizumab had higher rates of bacterial infections, respiratory tract infection (13.5 vs 5.1%, p<0.001), genitourinary system infection, (9.7% vs 3.8%, p<0.001) gastrointestinal tract infection (12.6% vs 3.5%, p<0.001), skin infection (8.4% vs 3%, p<0.001) and Ear, Nose, throat infection (11% vs 4.4%, p<0.001). In addition, risk of bacterial infection was higher among 940 patients treated with Ustekinumab than those not treated with Ustekinumab.

Conclusion

Significantly increased risk found among IBD patients treated with biologic agents; clinicians should consider the increased susceptibility to bacterial infections when deciding which biological agent to prescribe to their asthma patients

Introduction

Short bowel syndrome (SBS) is a critical clinical condition that occurs when, following multiple intestinal resections, the residual small bowel in continuity is ≤200 cm. SBS is associated with intestinal failure (IF) when the intestinal absorptive function is impaired, requiring intravenous administration of nutritional or electrolyte supplements. Crohn’s disease (CD) is one of the most frequent causes of SBS in adults

Aims & Methods

This study aimed to identify clinical predictive factors of SBS in CD patients (pts). We conducted a prospective study, enrolling consecutive outpatients with CD. Statistical univariate comparison for the primary outcome was assessed for continuous variables by the Mann-Whitney U and the Kruskal-Wallis ANOVA tests. Categorical variables were compared using the chi-square test. We also evaluated a multivariate logistic regression model to identify independent predictors of SBS.

Results

We enrolled 169 pts with CD (47.3% male, mean age 43.5 years [±14.1]). 45.5% of them were smokers; extraintestinal manifestations (EIMs) were present in 45.5% of pts, and 67.5% of pts had bowel resections (26.6% of them with more than one surgery). The median disease duration and median time between diagnosis and the first resection were 9 years (IQR 4-17) and 6.5 years (IQR 1-13), respectively. At baseline, 101 pts were on anti-TNF therapy, and considering the course of the disease, 20.1% of the pts were exposed to ≥3 biologics. 10% of pts had SBS and 5.3% IF. In univariate analysis, comparing patients with and without SBS, the following variables were statistically different: disease duration (p=0.000), upper gastrointestinal disease location (p=0.001), ileocolonic location (p=0.008), stenosing behavior (p=0.040), perianal disease (p=0.000) and time from CD diagnosis to initiation of biological therapy (p=0.002). At multivariate analysis, disease duration (OR 1.2, 95% CI 1.12-1.42, p=0.000) and perianal disease (OR 4.3, 95% CI 0.99-19.27, p=0.050) resulted independently associated with the development of SBS. Conversely, the time from diagnosis of CD to start biological therapy resulted in an inverse association with the onset of SBS (OR 0.8, 95% CI 0.74-0.97, p=0.016). This latter finding could be due to the late use of biological therapy in patients with less severe disease.

Conclusion

Our data identify clinical characteristics allowing gastroenterologists to predict the risk of developing SBS in a cohort of pts with CD. Further studies would be needed to confirm our results.

References

Funded by:2.1 "Rafforzamento e potenziamento della ricerca biomedica del SSN", finanziato dall’Unione europea–NextGenerationEU, CUP C53C22001140007. 2022 PNRR Project "Changing the future of intestinal failure in intestinal chronic inflammation: towards innovative predictive factors and therapeutic targets"code:PNRR-MAD-2022-12376791.