Introduction

Anti-TNF therapy has revolutionised the treatment of patients with Crohn’s disease (CD) and ulcerative colitis (UC). However, primary resistance or loss of efficacy are serious clinical challenges. Therapeutic drug monitoring (TDM) could help to manage these unfavourable therapeutic outcomes. The measurement of anti-TNF drug levels (DL) with point-of-care tests (POCT) is fast, simple tool to guide the therapy. TDM can be performed reactively in patients with active disease and proactively in asymptomatic patients. Nevertheless, the optimal utilization of TDM is still debated.

Aims & Methods

Our aim was to evaluate the impact of proactive and reactive TDM on the medium-term course of inflammatory bowel disease. We enrolled patients with UC and CD who were treated at our department with infliximab or adalimumab and underwent reactive or proactive TDM with POCT method between October 2021 and September 2023. We examined the types of therapeutical decision (dose intensification, switch within or out of class) were performed knowing DL and how the changes have affected the half-yearly outcome. Laboratory findings such as C-reactive protein (CRP), iron, albumin, haemoglobin, platelet, stool calprotectin level and calculated disease activity indices, Crohn’s disease activity index (CDAI), Harvey-Bradshaw Index (HBI), partial Mayo score (pMayo) and Simple clinical colitis activity index (SCCAI) were analysed at baseline and after 6 months. Statistical analysis was carried out with Graphpad Prism and SPSS.

Results

175 patients were enrolled, 80 men, 95 women, median age was 38 (IQR 30-50 years). 81 UC and 94 CD patients. In 79 cases proactive, in 96 cases reactive TDM was performed. In the reactive group the CRP (5.9 vs 12.2 mg/l, p=0.010), platelet count (278.3 vs 314.5 G/l, p=0.024) and the four activity indices (CDAI p=0.004, HBI p=0.0004, SCCAI p<0.0001, pMayo p<0.0001) were significantly higher, the albumin level (46.5 vs 45 g/l, p=0.019) was significantly lower compared to the proactive group at baseline. In the reactive group CRP (12.2 vs 5.7 mg/l, p=0.0083) and albumin level (46.5 vs 45 g/l p=0.0186) and all examined activity indices (CDAI p<0.0001, HBI p=0.0003, SCCAI p<0.0001, pMayo p=0.0002) changed significantly after 6 month from baseline. In the proactive group the lowering of SCCAI (p=0.0232), pMayo (p=0.0077) and CDAI (p=0.0471) were significant comparing baseline and 6-month parameters. Between the proactive and reactive groups no significant difference was found at month 6. In 41 (52%) cases in the proactive group subtherapeutical DL was found. Within these cases in CD patients CDAI (p=0.035, OR:1.02, 95%CI: 1.0-1.05) had a significant predictive value for the half-yearly outcome, in UC platelet count appeared to be nearly significant (p=0.097, OR: 1.07, 95%CI: 0.99-1.15) as a predictive factor. In 41 (52%) of the proactively measured cases no intervention was done, 27 (34%) dose-intesification, 5 (6%) de-escalation, 5 (6%) stop and 2 (3%) switch was carried out. In the reactively measured group 55 patients (57%) had subtherapeutical DL. In the reactive group no therapeutical change happened in 25 cases (26%), 42 (44%) underwent dose-intensification, 29 (30%) had switch (13 within class, 16 out of class).

Conclusion

We found no difference between the proactive and reactive drug level monitoring methods with POCT. Both affected the decision-making process and presented beneficial effect for medium-term and helped to achieve stride therapy goals.

Introduction

High-quality endoscopy in IBD is associated with better clinical outcomes, while quality measurement supports effective quality control. The European Society of Gastrointestinal Endoscopy recommends using nine performance measures, depending on the indication for endoscopic examination in IBD.

Aims & Methods

Our study aimed to compare colonoscopy quality between tertiary and secondary referral centers for IBD patients, based on endoscopic reports. In this cross-sectional study, colonoscopy reports of IBD patients were analyzed. At our tertiary center, we consecutively enrolled patients over 18 years old with established IBD between July and October 2024, using their available colonoscopy reports. The secondary care group included patients referred to our tertiary center, with the last existing report from secondary care used for analysis, while the tertiary care group consisted of our patients whose most recent report was similarly used. Nine key performance measures (indication, bowel preparation, photo documentation, ileal intubation, biopsy, endoscopic activity score, high-definition and chromoendoscopy use, and neoplasia detection) were evaluated based on colonoscopy reports. Patients were stratified by procedure indication (diagnostic, activity assessment, or surveillance) as well. Descriptive statistics, Welch’s, and Fisher’s exact tests were used to compare groups, with p-values <0.05 considered significant.

Results

Overall, 207 colonoscopy reports were assessed, of which 68/207 were performed at secondary care level. A total of 78/207 patients were diagnosed with Crohn’s disease, while unclassified diagnoses were noted only at secondary centers. Activity control (88% vs. 38%, p<0.001) and surveillance (8% vs. 0%, p=0.02) examinations were more common at the tertiary level. Bowel preparation was better at tertiary centers (Boston Bowel Preparation Scale [BBPS] 8.3±2.3 vs. 7.2±1.2; p=0.003), and use of BBPS was more frequent at higher levels of care (p<0.001). Disease activity scores were more commonly used at the tertiary level during activity control examinations (51.2% vs. 19.2%, p=0.004), while ileal intubation was also more frequent at the tertiary level (53% vs. 28%; p<0.001). Procedure and withdrawal times did not differ between levels in diagnostic or activity control examinations. Neoplasia detection was low, and biopsy rates were similar.

Conclusion

Quality indicator targets were met in neither secondary nor tertiary centers; however, wider investigation is needed to verify these results. Broad education can help to improve the quality of colonoscopy in IBD care.

Introduction

Iron deficiency anaemia (IDA) is a common comorbidity in inflammatory bowel diseases (IBD). Previous studies have already showed the predictive value of anaemia on hospitalization and mortality rates, however, these studies did not focus on the effect of IDA on patients with clinical and biochemical remission, however, due to the ethiopathology, certain effects are hypothesized.

Aims & Methods

This was a multicenter retrospective real-life cohort study assessing the effect of IDA on clinically and biochemically inactive IBD patients. We included patients from the outpatient setting who has been followed-up for a year. Patients with need of blood transfusion at baseline were excluded. IDA was defined as no clinical and biochemical activity, ferritin <30 μg/mL and transferrin saturation <20% with the presence of anemia. Primary outcome was disease aggravation, defined as need of change in the current treatment/hospitalization/abdominal surgery. Secondary outcome was proportion of major complications, defined as need of hospitalization/abdominal surgery. Pearson’s chi squared sample size calculation (n=720) was performed on our pilot results based on 200 IBD patients.

Results

In total, 711 patients (median age: 43.1 years [IQR: 32.3 - 49.6]; male/female ratio: 332/379; CD: 397, UC: 311; IDA/non-IDA 85/623) were enrolled. Mean follow-up period was 1.1±0.28 years. The presence of IDA increased the risk of disease aggravation (OR: 1.7) and major complications (OR: 2.8). Furthermore, male sex (OR: 0.6) and older age (OR: 0.8) were protective, and ileocoecal resection (OR: 2.0) and higher C-reactive protein levels (OR: 1.5) increased the disease aggravation.

Conclusion

IDA predicts the risk of relapse at some degree in patients with clinical and biochemical remission in the outpatient setting. IDA may help to identify underlying disease activity in patients with clinical and biochemical remission in time, therefore, we recommend to be implemented in the treat-to-target approach.

Introduction

Bowel urgency is one of the most bothersome symptoms of ulcerative colitis (UC) and have a great impact on quality of life and psychosocial function. The Urgency Numerical Rating Scale (U-NRS) is desinged to ojectify this subjective symptom. It measures the degree of faecal urgency experienced over the past 24 hours by patients with UC on a scale of 0-10. We assumed that the scale has a large variance, as patients evaluate their own symptoms differently, the urge may be different quality for two patients with the same score.

Aims & Methods

The objective of our study was to investigate the possible components of urgency and refine the assessment of urgency. Patients with UC older than 18 years treated at our departments for at least 3 months and having complaints were enrolled in our study. The patients filled out our non-validated questionnaire with questions about fecal urgency (U-NRS), pain level, speed of urge, incontinence and lifestyle characteristics associated with incontinence. Statistical analysis was performed using STATA 18 program.

Results

263 patients were enrolled, median age was 39.5 years, the mean of disease duration was 11.7±9.2 years. The mean U-NRS score was 3.2±3.2, 32% (84/263) had 0 score and 3% (9/263) has 10 score. 12% of the patients (n=31) felt most difficult to hold mucus, 37% (n=97) stool and 29% (n=76) other secretions. 8% (n=22) had urge with every stool in the last 24 hours, 36% (n=95) had less than half of defecations. The speed of urge defined more the level of urgency than the pain level (R2=0.798 p<0.001, β=0.894 vs R²=0.805, p<0.001, β=0.117). The duration of faeces holding in the last 7 days had significant connection to U-NRS (R²=0.211, p<0.001, β=-0.46). Patients using public restroom at least once during the last week had significantly higher score on U-NRS than other patients (4.6±3.1 vs 2.4±3 p<0.001). 12% (31/263) used diaper. The usage of diapers was also significantly more often in patients with higher U-RNS score (5.2±3.2 vs 2.9±3.1,p<0.0001). Faecal leakage both during the day and night was significiantly higher with higher U-NRS score (p<0.001 for both). Patient reported outcome (PRO2) had a weak correlation with U-NRS (R²=0.14). However if we examine bloody stool, the stool number and difficulty of faecas holding seperately we got a significant and better correlation with urgency (R²=0.43). Patients with moderately severe-severe disease (PRO2 > 5) had a higher chance to have urgency (AUC=0.9). The possibility was higher to have urgency among patients with painful defecation (R²=0.41). The level of urgency, duration of faeces holding and the frequency of faeces holding problems had the strongest correlation with U-NRS (R²=0.83). Patients defined urgency with these parameters according to this result. We created score with them, level of urgency points + half of duration points + frequency, which showed a good model to refine the definition of urgency (R²=0.83).

Conclusion

Bowel urgency affects UC patients' lives and is associated with more severe disability. Bowel urgency is common in UC affecting about two-third of patients and associates with more severe activity of UC. Fecal urgency can characterize with the level of urgency, duration of faeces holding and the frequence of stool more accurately than a single, subjective numeric scale. A new scoring system is needed to more accurately assess patients' complaints in this area and to objectify severity.

Disclosure

The authors have no potential conflict of interest to disclose

Introduction

Anaemia develops through several pathomechanisms (e.g., occult bleeding, mucosal inflammation, medications) in inflammatory bowel disease (IBD). In true iron deficiency anaemia (IDA) biochemical markers are not elevated, however, due to the pathomechanism, activity at some degree is presumed.

Aims & Methods

Our aim was to compare the one-year disease course of IBD patients with IDA compared to non-anaemic patients. This was a retrospective, double centre, cohort study, including a tertiary referral IBD centre and a secondary IBD centre. The study was carried out between June 2020 and November 2022. IDA was defined as CRP >10 μg/ml, ferritin <30 μg/ml and transferrin saturation <20 % with the presence of anaemia. Biochemical activity was defined as CRP >10mg/l, and severe anaemia as haemoglobin <100 g/l. Baseline laboratory data was obtained. Outcomes were all complications during the one-year follow-up period, including introduction of new treatment, treatment escalation, corticosteroid treatment and major complications (hospitalization and abdominal surgery).

Results

In total, 713 consecutive patients (median age 43 years [IQR: 33 - 57]; male/female ratio 335/378; CD/UC ratio 402/311) were involved in our study, 195 patients (27.3 %) from the secondary and 518 patients (72.7 %) from the tertiary referral centre. Median follow-up period was 1.06 [IQR: 0.98 – 1.13] years. IDA (OR: 2.745; p<0.001) increased the risk of all complications, including major complications (OR: 2.606; p=0.002), except abdominal surgery. The anaemia increased the risk of all outcomes, and the severity of anaemia increased the prevalence of major complications (p<0.001). CRP level was associated with the severity of anaemia (p<0.001).

Conclusion

IDA was a predictor of worse one-year outcomes, including introduction of new therapeutic agent, treatment escalation, corticosteroid admission and major complications despite the absence of inflammation. In conclusion, IDA should be involved in the treat to-target approach, and should be monitored tightly. Furthermore, due to the worse one-year outcomes, we suggest therapeutic intervention, in addition to the iron therapy. In addition, the severity of anaemia correlates with the prevalence of major complications.

Introduction

Inflammatory Bowel Diseases (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, mostly invasive, time-consuming, and expensive. The faecal biomarker can help to monitor the disease activity and therapeutic response by simple and non-invasively. Faecal Calprotectin (FC) is the gold-standard, but it has many disadvantages. We previously described that the correlation between the faecal Plasminogen activator inhibitor type 1 (PAI-1) (FP) level and the endoscopic activity and therapeutic response promote that it could be used as a novel non-invasive faecal biomarker in IBD diagnosis. Moreover, the faecal PAI-1 protein level is stable at room temperature and 4°C.

Aims & Methods

To observe the exact faecal biomarker potential, we aimed to define the FP level of IBD patients and subjects with other gastrointestinal (GI) diseases and compare it with the FC. Faecal samples were collected from 128 patients with IBD (CD-active: 18, CD-inactive: 10, UC-active: 20, UC-inactive: 10) and other GI diseases [colorectal cancer (CRC): 20, diverticulosis [DIV]: 21, irritable bowel syndrome [IBS]: 10, adenoma: 10) and 9 healthy subjects. ELISA method was applied to define FP level, and it was validated for stool samples by us and 0.5 ng/g PAI-1 level was defined as the cut-off value. For FC observation diagnostic FC ELISA kit (Orgentec) was used. 50 mg/g cut-off value was applied at FC. Confusion matrix analysis was utilized to define Youden-index, positive predictive value (PPV), negative predictive value (NPV), accuracy, specificity, and sensitivity of the measured values.

Results

FP level was significantly higher in patients with active IBD compared to inactive and non-IBD subjects (0.64 vs 0.0 ng/g, p<0.0001). No significant differences were observed between CD-active and UC-active groups (0.46 vs 0.79 ng/g, p=0.65). In addition, FP concentrations were significantly increased in active IBD (0.76 pg/g) patients compared to inactive IBD (0.0 pg/g, p=0.0001), CRC (0.11 ng/g, p=0.02), DIV (0.05 ng/g, p=0.001), IBS (0.0 ng/g, p<0.0001), adenoma (0.0 ng/g, p<0.0001), and healthy (0.0 ng/g, p=0.0002) subjects. However, FC showed the same pattern as FP, except at the CRC, adenoma and DIV. In these groups, there were no significant differences compared to the active IBD (487.4 mg/g) subjects (vs CRC: 147.1 mg/g, p=0.09; p=; adenoma: 159.8, p=0.056. Confusion matrix analysis defined high specificity (83.5%) and moderate sensitivity (57.9%) values (TP: 22, FP: 14, FN: 17, TN: 71, PPV: 0.61, NPV: 0.816) at the FP measurements. Nevertheless, at FC levels 35.3% specificity and 94.7% sensitivity were measured (TP: 36, FP: 55, FN: 2, TN: 30, PPV: 0.396, NPV: 0.938). Calculated Youden-index was higher at the FP (0.41) compared to the FC (0.3). On the other hand, the accuracy of the FP is 75.6% and the FC is 53.6%. Based on the results of all FP levels measured (N=299) so far, the calculated values were specificity: 78%, sensitivity: 62%, PPV: 0.63, NPV: 0.78, Youden-index: 0.4, accuracy: 72.3%.

Conclusion

Our results suggest that the FP level selectively increased in the active IBD and discriminated more specifically from the other GI diseases compared to the FC. However, the sensitivity was lower, but it was improved by the increasing patient numbers at the pooled FP levels. Thus, the FP level could be useful in the diagnosis of IBD independently or combined with FC.

References

Jójárt B, Resál T, Kata D, Molnár T, Bacsur P, Szabó V, Varga Á, Szántó KJ, Pallagi P, Földesi I, Molnár T, Maléth J, Farkas K. Plasminogen Activator Inhibitor 1 Is a Novel Faecal Biomarker for Monitoring Disease Activity and Therapeutic Response in Inflammatory Bowel Diseases. J Crohns Colitis. 2024 Mar 1;18(3):392-405. doi: 10.1093/ecco-jcc/jjad160. PMID: 37751311; PMCID: PMC10906952.

Introduction

Usability of subcutaneous vedolizumab (SC VDZ) in inflammatory bowel diseases (IBD, ulcerative colitis [UC], Crohn’s disease [CD]) have proved via clinical trials, while real-world data collection is ongoing. Experiences of Central-European population and assessment of patient’s perspectives are lacking.

Aims & Methods

Our study aimed to evaluate the real-world efficacy, safety and patient’s preferences of SC VDZ maintenance treatment after switching from intravenous (IV) formulation in a Hungarian IBD cohort. In this prospective, multicenter cohort study, IBD patients on maintenance IV VDZ treatment were enrolled, who switched to SC administration. Baseline was the day of the switch, while 52-week follow-up was set. Clinical and demographic data were collected, while serum VDZ level and CRP was measured at baseline and at w52. A non-validated questionary was filled by patients who were on drug at w12 recording patient’ satisfaction. Primary outcome was the drug survival rate at one year, while secondary outcomes were change in corticosteroid-free clinical (CSFR, based on physicians’ global assessment score PGA<1), and biochemical remission (BR, 5 mg/l³CRP) rates to w52, safety issues and patients’ preferences and change in serum drug levels.

Results

In total, 37 IBD patients were followed (15 CD and 22 UC, male/female ratio 45.9 %, median age 42.0 [IQR 34-49] years). In CD group, 66.7% were in CSFR and 60 % in BR, while in UC group 63.6% were in CSFR and 68.2 % in BR (p=0.55 and p=0.61). Overall, 29.7 % of patients ceased SC VDZ treatment after a median of 20 (IQR 6-26) weeks. Cessation was due to secondary response losing in 3/6 and 4/5 patients in CD and UC group. In case of 2 and one patients, SC treatment was terminated due to local reactions. One patient was fear of needle. Severe adverse event did not occur. Factors associated with discontinuation did not identify. The mean serum VDZ level has higher at w52 compared to baseline in CD and UC patients (CD: 8.9 ±6.9 to 30.6 ±17.8 ug/mL, p = 0.047; UC: 13.6±13.8 to 33.6±17.6 ug/mL, p = 0.001), while disease activity was stable. 84 % of the patients who filled the questionnaire were satisfied with injection, while only one patient found it difficult to inject.

Conclusion

Transition from IV to SC maintenance VDZ treatment is effective at one year, the overall survival rate is high presumably due to the elevated serum drug levels. Severe safety issue did not raise. Satisfaction of switched patients is high, which may improve treatment adherence and save resources.

Disclosure

K.F. has received speaker’s honoraria from AbbVie, Janssen, Ferring, Takeda, and Goodwill Pharma. T.M. has received speaker’s honoraria from MSD, AbbVie, Egis, Goodwill Pharma, Takeda, Pfizer, Janssen, Sandoz, MundiPharma, Phytotec, Roche, Fresenius, and Teva. ​Remaining authors have no conflict of interest to declare.